- 1Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
- 2Department of Pharmaceutical Botany, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
- 3Department of Environmental Sciences, Universidad de Santiago de Chile, Santiago de Chile, Chile
Berberine-containing plants have been traditionally used in different parts of the world for the treatment of inflammatory disorders, skin diseases, wound healing, reducing fevers, affections of eyes, treatment of tumors, digestive and respiratory diseases, and microbial pathologies. The physico-chemical properties of berberine contribute to the high diversity of extraction and detection methods. Considering its particularities this review describes various methods mentioned in the literature so far with reference to the most important factors influencing berberine extraction. Further, the common separation and detection methods like thin layer chromatography, high performance liquid chromatography, and mass spectrometry are discussed in order to give a complex overview of the existing methods. Additionally, many clinical and experimental studies suggest that berberine has several pharmacological properties, such as immunomodulatory, antioxidative, cardioprotective, hepatoprotective, and renoprotective effects. This review summarizes the main information about botanical occurrence, traditional uses, extraction methods, and pharmacological effects of berberine and berberine-containing plants.
Introduction
Berberine
Berberine(5,6-dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a] quinolizinium) Figure 1, is a nonbasic and quaternary benzylisoquinoline alkaloid, a relevant molecule in pharmacology and medicinal chemistry. Indeed, it is known as a very important natural alkaloid for the synthesis of several bioactive derivatives by means of condensation, modification, and substitution of functional groups in strategic positions for the design of new, selective, and powerful drugs (Chen et al., 2005).
Traditional Use of Berberine-Containing Species
In the Berberidaceae family, the genus Berberis comprises of ~450–500 species, which represent the main natural source of berberine. Plants of this genus are used against inflammation, infectious diseases, diabetes, constipation, and other pathologies (Singh A. et al., 2010). The oldest evidence of using barberry fruit (Berberis vulgaris) as a blood purifying agent was written on the clay tablets in the library of Assyrian emperor Asurbanipal during 650 BC (Karimov, 1993). In Asia, the extensive use of the stem, stem bark, roots, and root bark of plants rich in berberine, particularly Berberis species, has more than 3000 years of history. Moreover, they have been used as raw material or as an important ingredient in Ayurvedic and traditional Chinese medicine (Birdsall, 1997; Kirtikar and Basu, 1998; Gupta and Tandon, 2004; Kulkarni and Dhir, 2010). In Ayurveda, Berberis species have been traditionally used for the treatment of a wide range of infections of the ear, eye, and mouth, for quick healing of wounds, curing hemorrhoids, indigestion and dysentery, or treatment of uterine and vaginal disorders. It has also been used to reduce obesity, and as an antidote for the treatment of scorpion sting or snakebite (Dev, 2006). Berberine extracts and decoctions are traditionally used for their activities against a variety of microorganisms including bacteria, viruses, fungi, protozoa, helminthes, in Ayurvedic, Chinese, and Middle-Eastern folk medicines (Tang et al., 2009; Gu et al., 2010).
In Yunani medicine, Berberis asiatica has multiple uses, such as for the treatment of asthma, eye sores, jaundice, skin pigmentation, and toothache, as well as for favoring the elimination of inflammation and swelling, and for drying ulcers (Kirtikar and Basu, 1998). Decoction of the roots, and stem barks originating from Berberis aristata, B. chitria, and B. lycium (Indian Berberis species), have been used as domestic treatment of conjunctivitis or other ophthalmic diseases, enlarged liver and spleen, hemorrhages, jaundice, and skin diseases like ulcers (Rajasekaran and Kumar, 2009). On the other hand, the use of decoction of Indian barberry mixed with honey has also been reported for the treatment of jaundice. Additionally, it has been reported the use of decoction of Indian barberry and Emblic myrobalan mixed with honey in the cure of urinary disorders as painful micturition (Kirtikar and Basu, 1998). Numerous studies dealing with its antimicrobial and antiprotozoal activities against different types of infectious organisms (Vennerstrom et al., 1990; Stermitz et al., 2000; Bahar et al., 2011) have been assessed so far. Moreover, it has been used to treat diarrhea (Chen et al., 2014) and intestinal parasites since ancient times in China (Singh and Mahajan, 2013), and the Eastern hemisphere, while in China it is also used for treating diabetes (Li et al., 2004).
Nowadays, a significant number of dietary supplements based on plants containing berberine (Kataoka et al., 2008) are used for reducing fever, common cold, respiratory infections, and influenza (Fabricant and Farnsworth, 2001). Another reported use for berberine-containing plants is their application as an astringent agent to lower the tone of the skin. Also, positive effects were observed on the mucous membranes of the upper respiratory tract and gastrointestinal system with effects on the associated ailments (Chen et al., 2014; Yu et al., 2016).
In southern South America leaves and bark of species of the genus Berberis are used in traditional medicine administered for mountain sickness, infections, and fever (San Martín, 1983; Houghton and Manby, 1985; Anesini and Perez, 1993).
Furthermore, there are other genera which contain berberine. The genus Mahonia comprises of several species that contain berberine. Within them, M. aquifolium has been traditionally used for various skin conditions. Due to its main alkaloid (berberine), is known to be used in Asian medicine for its antimicrobial activity. Coptidis rhizoma (rhizomes of Coptis chinensis), another plant which contains berberine, is a famous herb very frequently used in traditional Chinese medicine for the elimination of toxins, “damp-heat syndromes”, “purge fire”, and to “clear heat in the liver” (Tang et al., 2009). Table 1 gathers a synthesis of the main traditional uses of species containing berberine.
Botanical Sources of Berberine
Berberine has been detected, isolated, and quantified from various plant families and genera including Annonaceae (Annickia, Coelocline, Rollinia, and Xylopia), Berberidaceae (Berberis, Caulophyllum, Jeffersonia, Mahonia, Nandina, and Sinopodophyllum), Menispermaceae (Tinospora), Papaveraceae (Argemone, Bocconia, Chelidonium, Corydalis, Eschscholzia, Glaucium, Hunnemannia, Macleaya, Papaver, and Sanguinaria), Ranunculaceae (Coptis, Hydrastis, and Xanthorhiza), and Rutaceae (Evodia, Phellodendron, and Zanthoxyllum) (Table 2). The genus Berberis is well-known as the most widely distributed natural source of berberine. The bark of B. vulgaris contains more than 8% of alkaloids, berberine being the major alkaloid (about 5%) (Arayne et al., 2007).
Berberine is also widely present in barks, leaves, twigs, rhizomes, roots, and stems of several medicinal plants species, including Argemone mexicana (Etminan et al., 2005), Berberis aristata, B. aquifolium, B. heterophylla, B. beaniana, Coscinium fenestratum (Rojsanga and Gritsanapan, 2005), C. chinensis, C. japonica, C. rhizome, Hydratis canadensis (Imanshahidi and Hosseinzadeh, 2008), Phellodendron amurense, P. chinense, Tinospora cordifolia (Khan et al., 2011), Xanthorhiza simplicissima (Bose et al., 1963; Knapp et al., 1967; Sato and Yamada, 1984; Steffens et al., 1985; Inbaraj et al., 2001; Liu et al., 2008a; Srinivasan et al., 2008; Vuddanda et al., 2010). Several researches found that berberine is widely distributed in the barks, roots, and stems of plants, nevertheless, bark and roots are richer in berberine compared to other plant parts (Andola et al., 2010a,b). In the Papaveraceae family, Chelidonium majus is another important herbal source of berberine (Tomè and Colombo, 1995). An important number of plants for medicinal use, such as Coptidis rhizoma and barberry, are the natural sources with the highest concentration of berberine. Barberries, such as Berberis aristata, B. aquifolium, B. asiatica, B. croatica, B. thunbergii, and B. vulgaris, are shrubs grown mainly in Asia and Europe, and their barks, fruits, leaves, and roots are often widely used as folk medicines (Imanshahidi and Hosseinzadeh, 2008; Kosalec et al., 2009; Andola et al., 2010c; Kulkarni and Dhir, 2010). Different research groups have reported that maximum berberine concentration accumulates in root (1.6–4.3%) and in most of the Berberis species, plants that grow at low altitude contain more berberine compared to higher altitude plants (Chandra and Purohit, 1980; Mikage and Mouri, 1999; Andola et al., 2010a). However, a correlation could not be established within the results of berberine concentration regarding to species and season of the year (Srivastava et al., 2006a,c; Andola et al., 2010c; Singh et al., 2012). Comparative studies of berberine concentration contained in different species of the same genus have been reported, e.g., higher berberine content in B. asiatica (4.3%) in comparison to B. lycium (4.0%), and B. aristata (3.8%). Meanwhile, Srivastava et al. (2004) documented a higher berberine content in root of B. aristata (2.8%) compared with B. asiatica (2.4%) (Andola et al., 2010a). Seasonal variation of berberine concentration has been reported, e.g., the maximum yield of berberine for B. pseudumbellata was obtained in the summer harvest, and was 2.8% in the roots and 1.8% for the stem bark, contrary to that reported in the roots of B. aristata, where the berberine concentration (1.9%) is higher for the winter harvest (Rashmi et al., 2009). These variations may be caused to multiple factors, among which stand out: (i) the intraspecific differences, (ii) location and/or, (iii) the analytical techniques used. Table 2 gathers a synthesis of the main species containing berberine.
Extraction Methods
Berberine, a quaternary protoberberine alkaloid (QPA) is one of the most widely distributed alkaloid of its class. Current studies suggest that isolation of the QPA alkaloids from their matrix can be performed using several methods. The principles behind these methods consist of the interconversion reaction between the protoberberine salt and the base. The salts are soluble in water, stable in acidic, and neutral media, while the base is soluble in organic solvents. Thus during the extraction procedure, the protoberberine salts are converted in their specific bases and further extracted in the organic solvents (Marek et al., 2003; Grycová et al., 2007).
In the case of berberine, the classical extraction techniques like maceration, percolation, Soxhlet, cold or hot continuous extraction are using different solvent systems like methanol, ethanol, chloroform, aqueous, and/or acidified mixtures. Berberine's sensitivity to light and heat is the major challenge for its extraction. Hence, exposure to high temperature and light could lead to berberine degradation and thus influencing its matrix recovery. In his study Babu et al. (2012) demonstrated that temperature represent a crucial factor in both extraction and drying treatments prior extraction. The yield of berberine content in C. fenestratum stem tissue samples was higher in case of samples dried under the constant shade with 4.6% weight/weight (w/w) as compared to samples dried in oven at 65°C (1.32% w/w) or sun drying (3.21% w/w). As well hot extraction procedure with methanol or ethanol at 50°C gave lower extraction yields when compared with methanol or ethanol cold extraction at −20°C. Thus, berberine content in the shade-dried samples was 4.6% (w/w) for methanolic cold extraction and 1.29% (w/w) for methanolic hot extraction (Babu et al., 2012).
Along with extraction temperature, the choice of solvents is considered a critical step in berberine extraction as well (Figure 2). As seen in Table 3, methanol, ethanol, aqueous or acidified methanol or ethanol are the most used extraction solvents. The acidified solvents (usually with the addition of 0.5% of inorganic or organic acids) are used to combine with free base organic alkaloids and transform them in alkaloid salts with higher solubility (Teng and Choi, 2013). The effect of different inorganic acids like hydrochloric acid, phosphoric acid, nitric acid, and sulfuric acid as well as the effect of an organic acid like acetic acid were tested on berberine content and other alkaloids in rhizomes of Coptis chinensis Franch by Teng and Choi (2013). In this case, 0.34% phosphoric acid concentration was considered optimal. Moreover, when compared to other classical extraction techniques like reflux and Soxhlet extraction, the cold acid assisted extraction gave 1.1 times higher berberine yields.
Table 3. Extraction and detection methods for berberine in different herbal and biological matrixes.
Large solvent volumes and long extraction time represent other drawbacks of conventional extraction methods (Mokgadi et al., 2013). For example, Rojsanga and Gritsanapan (2005) used maceration process to extract 100 g of C. fenestratum plant material with a total volume of 3,200 mL solvent (80% ethanol) over a period of 416 h. Furthermore, in a different study, Rojsanga et al. (2006) used several classical extraction techniques like maceration, percolation, and Soxhlet extraction to extract the berberine from C. fenestratum stems. This time even if the extracted plant material was in a lower amount than the previous study (30 vs. 100 g), large solvent volumes (2,000 mL for maceration, 5,000 mL for percolation, and 600 mL for Soxhlet extraction) over long time periods (7 days for maceration and 72 h for Soxhlet extraction) were employed (Rojsanga and Gritsanapan, 2005; Rojsanga et al., 2006).
Large solvent volumes are characteristic for other conventional methods too. Shigwan et al. (2013) extracted berberine from Berberis aristata and B. tinctoria powdered stem bark (800 g) using hot extraction (50°C for 3 h) with 2,500 mL methanol (Shigwan et al., 2013).
Even though conventional methods are widely used in berberine extraction, a number of other different methods have been developed lately. This led to an improved extraction efficiency, a decreased extraction time and solvents' volumes used in the extraction. Thus, ultrasound assisted solvent extraction (USE), microwave-assisted solvent extraction (MAE), ultrahigh pressure extraction (UPE), and supercritical fluid extractions (SFE), pressurized liquid extraction (PLE) have been successfully used as alternative extraction techniques with better results when compared with classical extraction methods.
Ultrasonically and microwave-assisted extraction are considered green, simple, efficient, and inexpensive techniques (Alupului et al., 2009).
Teng and Choi (2013) extracted berberine from Rhizome coptidis by optimized USE. Using response surface methodology, they identified that the optimal extraction conditions were 59% ethanol concentration, at 66.22°C within 46.57 min. A decrease in the extraction time (39.81 min) was obtained by Chang (2013). He used the combination of ionic liquids solutions as green solvents with USE to extract berberine from Coptis chinensis in order to apply an environmentally friendly approach (Chang, 2013). Moreover, in their study, Xu et al. (2017) compared several extraction tehniques like USE, distillation, and Soxhlet extraction in order to establish an high-efficient method for phellodendrine, berberine, and palmatine extraction from fresh Phellodendron bark (Cortex phellodendri). In the case of berberine, the combination of simple or acidified solvent (water, ethanol, and methanol) with the adjustment of the specific setting characteristics to each extraction type enabled them to determine the highest extraction yield. They concluded that the use of USE and hydrochloric acid-acidified methanol were the most efficient in extracting berberine. The USE extraction yield was significantly higher when compared to distillation and Soxhlet extraction, with values of ~100 mg/g toward 50 and 40 mg/g berberine, respectively (Xu et al., 2017).
The important reduction in organic solvent and extraction time determined the increasing interest in MAE, too. Lately, MAE was used as a green and cost-effective alternative to conventional methods. Using central composite design, Satija et al. (2015) successfully optimized the MAE parameters in terms of irradiation power, time, and solvent concentration to extract berberine form Tinospora cardifolia. They compared two classical extraction techniques like maceration and Soxhlet extraction with MAE under optimized conditions (60% irradiation power, 80% ethanol concentration, and 3 min extraction time). The results showed that MAE extraction had the highest yield of berberine content with 1.66% (w/w) while Soxhlet and maceration had 1.04 and 0.28% (w/w), respectively. Their study is emphasizing the dramatic time reduction in case of MAE (3 min) when compared with Soxhlet extraction (3 h) and maceration (7 days) together with solvent and energy consumption (Satija et al., 2015).
Another novel extraction technique considered to be environmentally friendly is UPE. The interest toward this extraction technique is increasing because it presents several advantages toward classical extraction techniques like increased extraction yields, higher quality of extracts, less extraction time, and decreased solvent consumption (Xi, 2015). These are achieved at room temperature by applying different pressure levels (from 100 to 600 MPa) between the interior (higher values) and the exterior of cells (lower values) in order to facilitate the transfer of the bioactive compounds through the plant matrices in the extraction solvent (Liu et al., 2006, 2013). In the study regarding berberine content in Cortex phellodendri, Guoping et al. (2012) made a comparison between UPE, MAE, USE, and heat reflux extraction techniques. They observed that the higher extraction yield and the lower extraction time was obtained in case of UPE with 7.7 mg/g and 2 min extraction time toward reflux, USE and MAE with 5.35 mg/g and 2 h, 5.61 mg/g and 1 h. and 6 mg/g and 15 min, respectively (Guoping et al., 2012).
Super critical fluid extraction is another environmentally friendly efficient technique used in phytochemical extraction. Because the extraction is performed in the absence of light and oxygen, the degradation of bioactive compounds is reduced. Also, the inert and non-toxic carbon dioxide used as a main extraction solvent in combination with various modifiers (e.g., methanol) and surfactants (e.g., Tween 80) at lower temperatures and relatively low pressure, allows the efficient extraction of bioactive compounds (Liu et al., 2006; Farías-Campomanes et al., 2015). In case of berberine extraction from the powdered rhizome of Coptis chinensis Franch, the highest recovery of berberine was obtained when 1,2-propanediol was used as a modifier of supercritical CO2 (Liu et al., 2006).
Pressurized liquid extraction, also known as pressurized fluid extraction, pressurized solvent extraction, and accelerated solvent extraction (ASE) is considered a green technology used for compounds extraction from plants (Mustafa and Turner, 2011). Compared with conventional methods, PLE increases the extraction yield, decreases time and solvent consumption, and protects sensitive compounds. In their study, Schieffer and Pfeiffer (2001) compared different extraction techniques like PLE, multiple USE, single USE, and Soxhlet extraction in order to extract berberine from goldenseal (Hydrastis canadensis). When compared in terms of extraction yield the results are comparable, ~42 mg/g berberine, except single USE with slightly lower content (37 mg/g berberine). Big differences were observed in the extraction time, PLE requiring only 30 min for a single sample extraction compared to 2 h for multiple extraction techniques or 6 h for Soxhlet extraction (Schieffer and Pfeiffer, 2001).
When referring to berberine extraction from biological samples, the extraction process is relatively simple and involves several steps like sample mixing with extraction solvents (e.g., methanol, acetone, acetonitrile), vortex, centrifugation followed by supernatant evaporation under nitrogen stream (Table 3). Other extraction techniques like solid phase extraction (SPE) can also be applied.
Analytical Techniques
After extraction and purification, the separation and quantification of berberine are commonly resolved by chromatographic methods. According to literature studies, berberine determination in plants was predominantly performed using methods like UV spectrophotometry (Joshi and Kanaki, 2013), HPLC (Babu et al., 2012; Akowuah et al., 2014), HPTLC and TLC (Rojsanga and Gritsanapan, 2005; Arawwawala and Wickramaar, 2012; Samal, 2013), capillary electrophoresis (Du and Wang, 2010), while berberine content in biological fluids was mainly achieved by using LC-MS (Deng et al., 2008; Feng et al., 2010), UPLC-MS (Liu M. et al., 2015; Liu L. et al., 2016), UHPLC/Q-TOF-MS (Wu et al., 2015).
UV-Vis spectrophotometry can be considered as one of the most rapid detection methods for berberine quantitative analysis from plant extracts. Based on the Beer-Lambert law, berberine concentration can be determined according to its absorption maxima at 348 nm. Joshi and Kanaki (2013) quantified berberine in Rasayana churna samples in the range of 2–20 μg/mL, the interference with other compounds being avoided by the specific isolation of the alkaloid fraction (Joshi and Kanaki, 2013).
Next, high-performance liquid chromatography (HPLC) is a versatile, robust, and widely used technique for the qualitative and quantitative analysis of natural products (Sasidharan et al., 2011). This approach is widely used in berberine identification and quantification. Generally, the choices of stationary phase in berberine separation are variants of C18-based silica column (Table 3) with a mobile phase consisting of simple or acidified solvents like water, methanol, or acetonitrile, used as such or in combination with phosphate buffers. Normally, the identification and separation of berberine can be accomplished using either isocratic or gradient elution system. Berberine identification is further accomplished using high sensitivity UV or DAD (diode array detectors) detectors. For example, Shigwan et al. (2013) developed in his study a reverse phase HPLC method with photodiode array detection (PDA) to quantify berberine from Berberis aristata and B. tinctoria. They used a Unisphere-C18 column (5 μm, 4.6 × 150 mm) with an isocratic gradient of acidified water (with 0.1% trifluoroacetic acid) and acetonitrile (60:40, v/v) to elute berberine within 5 min. The developed method was reproducible, validated, precise, and specific for berberine quantification (with a concentration range between 0.2 and 150 μg/mL; Shigwan et al., 2013).
Two other commonly used techniques in berberine quantification are thin layer chromatography (TLC) and high performance thin layer chromatography (HTPLC). Sometimes, these methods are preferred over HPLC, offering the possibility of running several samples simultaneously along with the use of small amount of both samples and mobile phases (Samal, 2013). For these reasons, Samal (2013) used an HPTLC method to quantify berberine from A. mexicana L. using toluene and ethyl acetate (9:3, v/v) as mobile phases, and a silica gel plate as stationary phase, they developed a simple, rapid, and cost-effective method for berberine quantification. The LOD (0.120 μg) and LOQ (0.362 μg) of the method are in accordance with high-quality requirements.
Following the same principles (small sample volume, high separation efficiency, and short analysis time), capillary electrophoresis (CE) was successfully used in berberine analysis. Du and Wang (2010) used CE with end-column electrochemiluminescence (ECL) detection for berberine analysis in both tablets and Rhizoma coptidis. Using a 4 min analysis time, a small sample volume (3.3 nL) and a LOD of (5 × 10−9 g/mL), the developed method proved to be highly sensitive and with good resolution (Du and Wang, 2010).
Besides UV, HPLC, HTPLC, TLC, and CE, other detection methods like liquid chromatography coupled with mass spectrometry (LC/MS) are currently employed to quantify berberine in biological fluids. Generally, it is considered a powerful technique for the analysis of complex samples because it offers rapid and accurate information about the structural composition of the compounds, especially when tandem mass spectrometry (MSn) is applied. For example, Xu et al. (2015) developed a sensitive an accurate LC-MS/MS method to determine berberine and other seven components in rat plasma using multiple reactions monitoring (MRM) mode. Compounds separation was optimized using six different types of reverse-phase columns, and two different mobile phases (methanol–water and acetonitrile–water with different additives). Additives like formic acid, acetic acid, and ammonium acetate were added in different concentrations as follows: 0.1, 0.5, 1, and 2% for formic acid, 0.1, 0.5, 1, and 2% for acetic acid and 0.0001, 0.001, 0.01 mol/L for ammonium acetate. The method was also tested in terms of specificity, linearity, lower limit of quantification (LLOQ), precision, accuracy, and stability (Xu et al., 2015).
Antioxidant Effect
Under normal conditions, the body maintains a balance between the antioxidant and pro-oxidant agents (reactive oxygen species—ROS and reactive nitrogen species—RNS; Rahal et al., 2014).
The imbalance between pro and antioxidants occurs in case of increased oxidative stress (Bhattacharyya et al., 2014).
The oxidative stress builds up through several mechanisms: an increase in the production of reactive species, a decrease in the levels of enzymes involved in blocking the actions of pro-oxidant compounds, and/or the decrease in free radical scavengers (Pilch et al., 2014).
An experimental study demonstrated the effect of berberine on lipid peroxidation after inducing chemical carcinogenesis in small animals (rats). An increase in LPO (lipid peroxidation) was observed after carcinogenesis induction, but also its significant reversal after berberine administration (30 mg/kg). Berberine shows therefore at least partial antioxidant properties, due to its effect on lipid peroxidation (Thirupurasundari et al., 2009).
Other mechanisms involved in the antioxidant role of berberine are: ROS/RNS scavenging, binding of metals leading to the transformation/oxidation of certain substances, free-oxygen removal, reducing the destructiveness of superoxide ions and nitric oxide, or increasing the antioxidant effect of some endogenous substances. The antioxidant effect of berberine was comparable with that of vitamin C, a highly-potent antioxidant (Shirwaikar et al., 2006; Ahmed et al., 2015).
The increase in blood sugar leads to oxidative stress not by generating oxygen reactive species but by impairing the antioxidant mechanisms. Administration of berberine to rats with diabetes mellitus increased the SOD (superoxide dismutase) activity and decreased the MDA (malondialdehyde) level (marker of lipid peroxidation). This antioxidant effect of berberine could explain the renal function improvement in diabetic nephropathy (Liu et al., 2008b).
The oxidative stress plays an important role in the pathogenesis of many diseases. The beneficial effect of berberine is presumed to reside mostly in its antioxidant role.
Cardiovascular Effects of Berberine
Effect on Cardiac Contractility
The beneficial effect of berberine in cardiac failure was demonstrated in a study on 51 patients diagnosed with NYHA (New York Heart Association) III/IV cardiac failure with low left ventricular ejection fraction (LVEF) and premature ventricular contractions and/or ventricular tachycardia. These patients received tablets containing 1.2 g berberine/day, together with conventional therapy (diuretics, ACEI—angiotensin-converting-enzyme inhibitors, digoxin, nitrates) for 2 weeks. An increase in LVEF was observed in all patients after this period, but also a decrease in the frequency and complexity of premature ventricular contractions. The magnitude of the beneficial effect was in direct proportion with the plasma concentration of berberine (Zeng, 1999).
The Cardioprotective Effect During Ischemia
Berberine can provide cardio-protection in ischemic conditions by playing various roles at different levels: modulation of AMPK (AMP—activated kinase) activity, AKT (protein kinase B) phosphorylation, modulation of the JAK/STAT (Janus kinase/signal transducers and activators of transcription) pathway and of GSK3β (glycogen synthase kinase 3β; Chang et al., 2016). AMPK is an important enzyme playing an essential role in cellular metabolism and offering protection in ischemic conditions by adjusting the carbohydrate and lipid metabolism, the function of cell organelles (mitochondria, endoplasmic reticulum) and the apoptosis (Zaha et al., 2016).
Berberine activates the PI3K (phosphoinositide 3-kinase)/AKT pathway which is considered a compensatory mechanism limiting the pro-inflammatory processes and apoptotic events in the presence of aggressive factors. The activation of this pathway is associated with a reduction of the ischemic injury through the modulation of the TLR4 (toll-like receptor 4)-mediated signal transduction (Hua et al., 2007).
Several supporting data indicate that the JAK2/STAT3 signaling plays an important role in cardioprotection against ischemia-reperfusion injury (Mascareno et al., 2001).
GSK3β is a serine/threonine protein-kinase, an enzyme involved in reactions associated to important processes at the cellular level: metabolization, differentiation, proliferation, and apoptosis. Berberine inhibits this kinase, thereby exercising its cardioprotective effect (Park et al., 2014).
Effects on the Endothelium
Berberine induces endothelial relaxation by increasing NO production from arginine through the activity of eNOS (endothelial nitric oxide synthase) which is considered a key element in the vasodilation process. Besides increasing the NO level, it also up-regulates eNOS mRNA. Furthermore, berberine facilitates the phosphorylation of eNOS and its coupling to HSP 90 (heat shock proteins), which consequently increases NO production (Wang et al., 2009).
Moreover, berberine reduces endothelial contraction by reducing COX-2 expression. Any imbalance in COX 1 or 2 activity may alter the ratio between prothrombotic/antithrombotic and vasodilator/vasoconstrictor effects (Liu L. et al., 2015).
The beneficial effect of berberine on the TNFα-induced endothelial contraction was also recorded, as well as an increase in the level of PI3K/AKT/eNOS mRNA (Xiao et al., 2014).
The Role of Berberine in Atherosclerosis
Atherogenesis is a consequence of high blood lipid levels and is associated with inflammatory changes in the vascular wall. Berberine interferes with this process by up-regulating the expression of SIRT1 (silent information regulator T1) and by inhibiting the expression of PPARγ (peroxisome proliferator-activated receptor-γ). SIRT1 is a NAD-dependent deacetylase. The SIRT1 enzyme has many targets (PPARγ, p53), all playing different roles in atherogenesis (Chi et al., 2014).
The Role of Berberine in Lipid Metabolism
The effects of berberine on lipid metabolism are also the consequence of its effects on LDL cholesterol receptors. On one hand, these receptors are stabilized by an extracellular signal-regulated kinase (ERK)-dependent pathway, and on the other, berberine increases the activity of LDL receptors through the JNK pathway (Cicero and Ertek, 2009).
Moreover, berberine has an effect on ACAT (cholesterol acyltransferases), a class of enzymes that transform cholesterol into esters, thus playing an essential role in maintaining cholesterol homeostasis in different tissues. There are two types of ACAT enzymes, ACAT1, and ACAT2. ACAT1 is a ubiquitous enzyme, while ACAT2 can be found only in hepatic cells and enterocytes. Berberine influences the activity of ACAT2 without an effect on ACAT1, therefore reducing the intestinal absorption of cholesterol and decreasing its plasmatic level (Chang et al., 2009; Wang et al., 2014).
The hypolipidemic effect of berberine is also a result of its action on PCSK9 (proprotein convertase subtilisin kexin 9). This enzyme can attach itself to LDL receptors, leading to a decrease in LDL metabolization and an increase in its blood level (Xiao et al., 2012).
In a clinical trial, 63 patients with dyslipidemia were randomly divided in three groups. The first group was treated with berberine (1,000 mg/day), the second with simvastatin (20 mg/day) and the third with a combination of berberine and simvastatin. The authors reported a 23.8% reduction in LDL-C levels in patients treated with berberine, a 14.3% reduction in those treated with simvastatin and a 31.8% LDL-C reduction in the group treated with both simvastatin and berberine. This result demonstrates that berberine can be used alone or in association with simvastatin in the treatment of dyslipidemia (Kong et al., 2008).
The Role of Berberine in Glucose Metabolism
Many studies demonstrated that berberine lowers blood sugar, through the following mechanisms:
- Inhibition of mitochondrial glucose oxidation and stimulation of glycolysis, and subsequently increased glucose metabolization (Yin et al., 2008a).
- Decreased ATP level through the inhibition of mitochondrial function in the liver, which may be the probable explanation of gluconeogenesis inhibition by berberine (Xia et al., 2011).
- Inhibition of DPP 4 (dipeptidyl peptidase-4), a ubiquitous serine protease responsible for cleaving certain peptides, such as the incretins GLP1 (glucagon-like peptide-1) and GIP (gastric inhibitory polypeptide); their role is to raise the insulin level in the context of hyperglycemia. The DPP4 inhibition will prolong the duration of action for these peptides, therefore improving overall glucose tolerance (Al-masri et al., 2009; Seino et al., 2010).
Berberine has a beneficial effect in improving insulin resistance and glucose utilization in tissues by lowering the lipid (especially triglyceride) and plasma free fatty acids levels (Chen et al., 2011).
The effect of berberine (1,500 mg day) on glucose metabolism was also demonstrated in a pilot study enrolling 84 patients with type 2 diabetes mellitus. The effect, including on HbA1c, was comparable to that of metformin (1,500 mg/day), one of the most widely used hypoglycemic drugs. In addition, berberine has a favorable influence on the lipid profile, unlike metformin, which has barely any effect (Yin et al., 2008b).
Hepatoprotective Effect of Berberine
The hepatoprotective effect of berberine was demonstrated on lab animals (mice), in which hepatotoxicity was induced by doxorubicin. Pretreatment with berberine significantly reduced both functional hepatic tests and histological damage (inflammatory cellular infiltrate, hepatocyte necrosis; Zhao et al., 2012).
The mechanism by which berberine reduces hepatotoxicity was also studied on CCl4 (carbon tetrachloride)-induced hepatotoxicity. Berberine lowers the oxidative and nitrosamine stress and also modulates the inflammatory response in the liver, with favorable effects on the changes occurring in the liver. Berberine prevents the decrease in SOD activity and the increase in lipid peroxidation and contributes to the reduction in TNF-α, COX-2, and iNOS (inducible nitric oxide synthase) levels. The decrease in transaminase levels supports the hypothesis according to which berberine helps maintain the integrity of the hepatocellular membrane (Domitrović et al., 2011).
Nephroprotective Effect of Berberine
The chronic kidney damage occurring in time in patients with HT (hypertension) and DM (diabetes mellitus) is well known; it is mainly due to the atherosclerosis of the renal artery, caused by inflammation and oxidative stress. The protective effect of berberine on kidneys was studied on 69 patients suffering from both HT and DM, with blood pressure and blood sugar levels controlled with conventional medication. The patients received 300 mg berberine/day for 24 months, with 2-week interruptions every 5 months. The authors recorded lower CRP (C-reactive protein), MDA and SOD levels after treatment, but without significant changes in creatinine, arterial pressure, or glycaemia levels. These results support the renal protective effect of berberine through its anti-inflammatory and antioxidant effects (Dai et al., 2015).
Another animal study tested the renoprotective effect of berberine after administration of HgCl2 (mercury chloride). This substance induces hepato-renal damage by increasing the oxidative stress (increases lipid peroxidation and NO levels, and lowers glutathione and SOD levels as well as the activity of other protective enzymes). Administration of HgCl2 increased the AST (aspartate aminotransferase), ALT (alanine aminotransferase), and ALP (alkaline phosphatase) levels, compared to the control group. However, pretreatment with berberine lowered these enzymes significantly. In addition, both urea and creatinine levels were significantly increased in the HgCl2 group vs. the control group, and again pretreatment with berberine prevented these changes. Additionally, the authors recorded higher pro-oxidant and lower antioxidant levels in the intervention group. These data support the hepatic and renal protective effects of berberine. Other studies performed on animal models with CCl4−induced hepatotoxicity demonstrated the same effect (Othman et al., 2014).
In addition, berberine can lower the nephrotoxicity caused by cisplatine. In an animal study, berberine was administered in progressive doses of 1, 2, 3 mg/kg, orally, for 2 successive days, starting 2 days after cisplatine administration. After the last doses of berberine, the animals were sacrificed and the kidneys were examined by the pathologist. The results showed significant histological improvement and a reduction in NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), TNF α, COX2 an iNOS levels, all of which support the anti-inflammatory effect of berberine (Domitrović et al., 2013).
Immunomodulatory Effect of Berberine
The immunomodulatory effect of berberine was demonstrated in many experimental and clinical contexts.
In an experimental autoimmune myocarditis model, berberine contributed to mitigate the cardiac damage by: limiting the rise in anticardiac myosin antibodies, modulating the activity of certain STATs and blocking Th1 and Th2 cell differentiation, which play an important role in the pathogenesis of myocarditis (Liu X. et al., 2016).
Experimental autoimmune neuritis is an experimental animal model equivalent to the Guillain-Barre syndrome in humans. This neurologic syndrome is characterized by autoimmune injury of the peripheral nervous system. The beneficial effect of berberine on this animal model resided in its influence on cellular and humoral immunity through the inhibition of lymphocyte proliferation (especially CD4), and the decrease in pro-inflammatory cytokines (IL-6 and TNF α; Li et al., 2014).
Experimental autoimmune encephalomyelitis is an established model of multiple sclerosis. Multiple sclerosis is a one of the most common diseases of the central nervous system (CNS) and involves neurodegenerative and inflammatory processes, and autoimmune demyelination (Ransohoff et al., 2015). The blood-brain barrier permeability and changes in matrix metalloproteinase (MMP) levels in the cerebrospinal fluid and brain were studied using this model (Ma et al., 2010). MMPs may be involved in demyelination and their activity in tissues depends on the balance between their level and their tissue inhibitors. MMP2 and MMP9 are the main endoproteinases involved in the migration of lymphocytes in CNS and in altering the BBB (blood brain barrier) (Avolio et al., 2003). Berberine has a beneficial effect in experimental autoimmune encephalomyelitis by inhibiting the activity of MMP9, reducing BBB permeability and, consecutively, by decreasing the inflammatory cellular infiltration of the CNS (Ma et al., 2010).
The current therapy used for inflammatory bowel diseases, including glucocorticoids and immunosuppressive agents, has a low level of safety. The effect of berberine was studied in combination with 5-ASA (5-aminosalicylic acid) vs. 5-ASA alone using an experimental animal model with DSS (dextran sulfate sodium)-induced colitis. The authors analyzed the level of proinflammatory cytokines in the animal gut. A decrease in COX2, IL6, and IL23 mRNA levels was observed in animals treated only with 5-ASA, whereas animals treated with both 5-ASA and berberine had a reduction in mRNA levels for COX2, IL6, IL23 as well as for TNF alfa and IL12b. This beneficial effect could partially be attributed to the inhibition of NF-kB and the reduction in JAK2 phosphorylation (through the influence on the JAK/STAT pathway) by both 5-ASA and berberine (Li et al., 2015; Figure 3).
Figure 3. Therapeutic effects of berberine in vivo. Mechanisms of berberine in regulation of metabolism, immunity and oxidative reactions. Phosphodiesterase (PDE), cyclic 3′,5′-adenosine monophosphate (cAMP), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Janus kinase/signal transducers and activators of transcription (JAK/STAT), glycogen synthase kinase 3β (GSK3β), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), cholesterol acyltransferases (ACAT2), dipeptidyl peptidase-4 (DPP 4), proprotein convertase subtilisin kexin 9 (PCSK9).
Another study demonstrated that berberine increases the corticosteroid level in rats with experimentally-induced colitis. This engendered the theory that its beneficial effect may also be attributed to the increase in endogenous glucocorticoid levels, compounds with well-known therapeutic effect in inflammatory bowel disease (Minaiyan et al., 2011).
Conclusion
A review of the available scientific literature shows that the traditional medical uses of berberine-containing plants have been evaluated by modern pharmacological studies. Different species of berberine-rich plants have multiple pharmacological and therapeutic actions, such as antioxidant and immunomodulatory effects, protective action on the cardiovascular system, liver and kidney, endothelial relaxation, regulator on glucose metabolism and atherosclerosis, which can all be explained by the presence of berberine as well as other phyto constituents (when dealing with berberine-containing plant extracts). Moreover, the effects of berberine vary according to its origin (different plants or pharmaceutical products) and its concentration, depending on the very diverse extraction and detection techniques already described. Over time, modern extraction techniques were increasingly preferred to classical ones. Since classical methods are generally time- and solvent-consuming processes, modern extraction techniques such as USE, MAE, UPE, SFE, and PLE are seen as better alternatives to overcome these limitations. Furthermore, berberine, due to its antioxidant and anti-inflammatory effects, has several clinical applications in many disorders, from inflammatory conditions to the metabolic syndrome. However, there are some traditional uses that have not yet been completely elucidated, and further studies are needed. Therefore, extensive studies on the potential of plants containing berberine that have shown aforementioned pharmacological activities should go through additional in vitro and in vivo studies.
Author Contributions
MN, AM, JE, and RP have conceived and designed the structure of the manuscript, data collection, and drafting, as well as its revision. CB, GC, and AB have critically reviewed the manuscript. All authors have seen and agreed on the final version of the manuscript.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Acknowledgments
This article was published under the frame of the internal grant no. 4945/15/08.03.2016 of the Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
References
Abbasi, A. M., Dastagir, G., Hussain, F., and Sanaullah, P. (2005). Ethnobotany and marketing of crude drug plants in district Haripur, Pakistan. Pak. J. Plant Sci. 11, 103–114.
Abbasi, A. M., Khan, M. A., Ahmad, M., Zafar, M., Jahan, S., and Sultana, S. (2010). Ethnopharmacological application of medicinal plants to cure skin diseases and in folk cosmetics among the tribal communities of North-West Frontier Province, Pakistan. J. Ethnopharmacol. 128, 322–335. doi: 10.1016/j.jep.2010.01.052
Abbasi, A. M., Khan, M. A., Ahmad, M., Zafar, M., Khan, H., Muhammad, N., et al. (2009). Medicinal plants used for the treatment of jaundice and hepatitis based on socio-economic documentation. Afr. J. Biotechnol. 8, 1643–1650.
Abou-Donia, A. H. A., and El-Din, A. A. S. (1986). Phytochemical study of Argemone mexicana L. grown in Egypt. Egypt. J. Pharm. Sci. 25, 1–5.
Acharya, K. P., and Rokaya, M. B. (2005). Ethnobotanical survey of medicinal plants traded in the streets of Kathmandu valley. Sci. World 3, 44–48.
Adeyemi, A. A., Gbolade, A. A., Moody, J. O., Ogbole, O. O., and Fasanya, M. T. (2010). Traditional anti-fever phytotherapies in Sagamu and Remo north districts in Ogun State, Nigeria. J. Herbs. Spices Med. Plants 16, 203–218. doi: 10.1080/10496475.2010.511075
Adjanohoun, J. E., Aboobakar, N., and Dramane, K. (1996). Traditional Medicine and Pharmacopoeia: Contribution to Ethnobotanical and Floristic Studies in Cameroon. Porto-Novo: Technical and Research Commission (STRC) of the Organization of African Unity.
Ahmed, E., Arshad, M., Ahmad, M., Saeed, M., and Ishaque, M. (2004). Ethnopharmacological survey of some medicinally important plants of Galliyat Areas of NWFP, Pakistan. Asian J. Plant Sci. 3, 410–415. doi: 10.3923/ajps.2004.410.415
Ahmed, T., Gilani, A. U., Abdollahi, M., Daglia, M., Nabavi, S. F., and Nabavi, S. M. (2015). Berberine and neurodegeneration: a review of literature. Pharmacol. Rep. 67, 970–979. doi: 10.1016/j.pharep.2015.03.002
Ajali, U. (2000). Antibacterial activity of Enantia polycarpa bark. Fitoterapia 71, 315–316. doi: 10.1016/S0367-326X(99)00153-7
Akowuah, G. A., Okechukwu, P. N., and Chiam, N. C. (2014). Evaluation of HPLC and spectrophotometric methods for analysis of bioactive constituent berberine in stem extracts of Coscinium fenestratum. Acta Chromatogr. 26, 243–254. doi: 10.1556/AChrom.26.2014.2.4
Al-Douri, N. A. (2000). A survey of medicinal plants and their traditional uses in Iraq. Pharm. Biol. 38, 74–79. doi: 10.1076/1388-0209(200001)3811-BFT074
Ali, M., Shah, S. Z., Khan, M. S., Naz, M. F. R., and Zafar, A. (2018). Ethnobotanical study on the weeds of wheat crop in district Swabi, Khyber Pakhtunkhwa, Pakistan. Int. J. Biosci. 12, 363–374. doi: 10.12692/ijb/12.1.363-374
Al-masri, I. M., Mohammad, M. K., and Tahaa, M. O. (2009). Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine. J. Enzyme Inhib. Med. Chem. 24, 1061–1066. doi: 10.1080/14756360802610761
Al-Qura'n, S. (2009). Ethnopharmacological survey of wild medicinal plants in Showbak, Jordan. J. Ethnopharmacol. 123, 45–50. doi: 10.1016/j.jep.2009.02.031
Alupului, A., Calinescu, I., and Lavric, V. (2009). Ultrasonic vs. microwave extraction intensification of active principles from medicinal plants. Chem. Eng. Trans. 17, 1023–1028. doi: 10.3303/cet0917171
Andola, H. C., Gaira, K. S., Rawal, R. S., Rawat, M. S., and Bhatt, I. D. (2010a). Habitat-dependent variations in berberine content of Berberis asiatica Roxb. ex. DC. in Kumaon, Western Himalaya. Chem. Biodivers. 7, 415–420. doi: 10.1002/cbdv.200900041
Andola, H. C., Rawal, R. S., Rawat, M. S. M., Bhatt, I. D., and Purohit, V. K. (2010b). Variations of berberine contents in Berberis pseudumbellata: a high value medicinal shrub of west Himalaya, India. Med. Plants Int. J. Phytomed. Relat. Ind. 2, 111–115. doi: 10.5958/j.0975-4261.2.2.017
Andola, H. C., Rawal, R. S., Rawat, M. S. M., Bhatt, I. D., and Purohit, V. K. (2010c). Analysis of berberine content using HPTLC fingerprinting of root and bark of three Himalayan Berberis species. Asian J. Biotechnol. 2, 239–245. doi: 10.3923/ajbkr.2010.239.245
Anesini, C., and Perez, C. (1993). Screening of plants used in Argentine folk medicine for antimicrobial activity. J. Ethnopharmacol. 39, 119–128. doi: 10.1016/0378-8741(93)90027-3
Arawwawala, L. D. A. M., and Wickramaar, W. A. N. (2012). Berberine content in Coscinium fenestratum (Gaertn.) Colebr grown in Sri Lanka. Pharmacologia 3, 679–682. doi: 10.5567/pharmacologia.2012.679.682
Arayne, M. S., Sultana, N., and Bahadur, S. S. (2007). The berberis story: Berberis vulgaris in therapeutics. Pak. J. Pharm. Sci. 20, 83–92.
Atta-ur-Rahma, and Ahmad, H. (1992). An aporphine-benzylisoquinoline alkaloid from Berberis waziristanica. Phytochemistry 31, 1835–1836. doi: 10.1016/0031-9422(92)83163-S
Avolio, C., Ruggieri, M., Giuliani, F., Liuzzi, G. M., Leante, R., Riccio, P., et al. (2003). Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes. J. Neuroimmunol. 136, 46–53. doi: 10.1016/S0165-5728(03)00006-7
Babu, N. H. R., Thriveni, H. N., and Vasudeva, R. (2012). Influence of drying methods and extraction procedures on the recovery of berberine content in Coscinium fenestratum. J. Nat. Prod. Plant Resour. 2, 540–544.
Bahar, M., Deng, Y., Zhu, X., He, S., Pandharkar, T., Drew, M. E., et al. (2011). Potent antiprotozoal activity of a novel semi-synthetic berberine derivative. Bioorg. Med. Chem. Lett. 21, 2606–2610. doi: 10.1016/j.bmcl.2011.01.101
Baharvand-Ahmadi, B., Bahmani, M., Tajeddini, P., Naghdi, N., and Rafieian-Kopaei, M. (2016). An ethno-medicinal study of medicinal plants used for the treatment of diabetes. J. Nephropathol. 5, 44–50. doi: 10.15171/jnp.2016.08
Baldazzi, C., Leone, M. G., Casini, M. L., and Tita, B. (1998). Effects of the major alkaloid of Hydrastis canadensis L., berberine, on rabbit prostate strips. Phyther. Res. 12, 589–591. doi: 10.1002/(SICI)1099-1573(199812)12:8<589::AID-PTR347>3.0.CO;2-I
Bapna, S., Choudhary, P. K., Ramaiya, M., and Chowdhary, A. (2015). Antiplasmodial activity of Argemone mexicana: an in vivo and in vitro study. World J. Pharm. Res. 4, 1653–1663.
Bele, M. Y., Focho, D. A., Egbe, E. A., and Chuyong, B. G. (2011). Ethnobotanical survey of the uses Annonaceae around mount Cameroon. Afr. J. Plant Sci. 5, 237–247.
Betti, J. L., Caspa, R., Ambara, J., and Kourogue, R. L. (2013). Ethno-botanical study of plants used for treating malaria in a forest: savanna margin area, East region, Cameroon. Glob. J. Res. Med. Plants Indig. Med. 2, 692.
Betti, J. L., and Lejoly, J. (2009). Contribution to the knowledge of medicinal plants of the Dja Biosphere Reserve, Cameroon: plants used for treating jaundice. J. Med. Plants Res. 3, 1056–1065.
Bhandari, D. K., Nath, G., Ray, A. B., and Tewari, P. V. (2000). Antimicrobial activity of crude extracts from Berberis asiatica stem bark. Pharm. Biol. 38, 254–257. doi: 10.1076/1388-0209(200009)3841-AFT254
Bhattacharjee, S., Tiwari, K. C., Majumdar, R., and Misra, A. K. (1980). Folklore medicine from district Kamrup (Assam). Bull. Medic. Ethno. Bot. Res. 1, 447–460.
Bhattacharyya, A., Chattopadhyay, R., Mitra, S., and Crowe, S. E. (2014). Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol. Rev. 94, 329–354. doi: 10.1152/physrev.00040.2012
Birdsall, T. C. (1997). Berberine: therapeutic potential of an alkaloid found in several medicinal plants. Altern. Med. Rev. 2, 94–103.
Bonesi, M., Loizzo, M. R., Conforti, F., Passalacqua, N. G., Saab, A., Menichini, F., et al. (2013). Berberis aetnensis and B. libanotica: A comparative study on the chemical composition, inhibitory effect on key enzymes linked to Alzheimer's disease and antioxidant activity. J. Pharm. Pharmacol. 65, 1726–1735. doi: 10.1111/jphp.12172
Borokini, T. I., Clement, M., Dickson, N. J., and Edagbo, D. E. (2013). Ethnobiological survey of traditional medicine practice for fevers and headaches in Oyo State, Nigeria. Topclass J. Herb. Med. 2, 121–130.
Bose, B. C., Vijayvargiya, R., Saifi, A. Q., and Sharma, S. K. (1963). Chemical and pharmacological studies on Argemone mexicana. J. Pharm. Sci. 52, 1172–1175. doi: 10.1002/jps.2600521216
Bouquet, A. (1969). Féticheurs et Médecines Traditionnelles du Congo (Brazzaville). Mém. O.R.S.T.O.M. (Paris: Office la Rech. Sci. Tech. outre-mer) 36, 282.
Bouquet, A., and Debray, M. (1974). Plantes Médicinales de la Côte d'Ivoire. Paris Off. la Rech. Sci. Tech. Paris: Outre Mer 231p. (Travaux Doc. l'ORSTOM no. 32) Illus., col. illus. Geog 5.
Burkill, H. M. (1985). The Useful Plants of West Tropical Africa. London: Royal Botanic Gardens, Kew.
Bushra, I., Kishwar, S., Qureshi, R. A., and Saddiqa, M. (2000). A checklist of plants of Bhogarmang, Siran Valley NWFP, Pakistan. Hamdard Med. 43, 62–76.
Buzas, A., and Egnell, C. (1965). On the presence of quinidine in addition to berberine alkaloids in the barks of Enantia pilosa and Enantia polycarpa (Annonaceae). Ann. Pharm. Fr. 23, 351.
Castleman, M. (1991). The Healing Herbs: The Ultimate Guide to the Curative Powers of Nature's Medicine. Emmaus: Rodale Press.
Chakravarti, K. K., Dhar, D. C., and Siddiqui, S. (1950). Alkaloidal constituents of the bark of Berberis aristata. J. Sci. Ind. Res. 9, 161–164.
Chan, C.-O., Chu, C.-C., Mok, D. K., and Chau, F.-T. (2007). Analysis of berberine and total alkaloid content in Cortex phellodendri by near infrared spectroscopy (NIRS) compared with high-performance liquid chromatography coupled with ultra-visible spectrometric detection. Anal. Chim. Acta 592, 121–131. doi: 10.1016/j.aca.2007.04.016
Chandra, P., and Purohit, A. N. (1980). Berberine contents and alkaloid profile of Berberis species from different altitudes. Biochem. Syst. Ecol. 8, 379–380. doi: 10.1016/0305-1978(80)90040-X
Chang, T.-Y., Li, B.-L., Chang, C. C., and Urano, Y. (2009). Acyl-coenzyme A:cholesterol acyltransferases. Am. J. Physiol. Endocrinol. Metab. 297, E1–E9. doi: 10.1152/ajpendo.90926.2008
Chang, W., Li, K., Guan, F., Yao, F., Yu, Y., Zhang, M., et al. (2016). Berberine pretreatment confers cardioprotection against ischemia-reperfusion injury in a rat model of type 2 diabetes. J. Cardiovasc. Pharmacol. Ther. 21, 486–494. doi: 10.1177/1074248415627873
Chatterjee, D. R. (1951). Plant alkaloids. I. Berberis floribunda. J. Indian Chem. Soc. 28, 225–228.
Chatterjee, R., and Banerjee, A. (1953). Plant alkaloids. V. Berberis lambertii. J. Indian Chem. Soc. 30, 705–707.
Chatterjee, R., Guha, M. P., and Das Gupta, A. K. (1952). Plant alkaloids. IV. Berberis himalaica and B. tinctoria. J. Indian Chem. Soc. 29, 921–924.
Chaudhury, R. H. N., Guha, A., Chaudhury, R., and Pal, D. C. (1980). Ethnobotanical uses of herbaria-2. J. Econ. Taxon. Bot. 1, 163–168.
Chen, A. H. (1981). Studies on the analysis of alkaloids of Phellodendron wilsonii Hay. et Kaneh. Kaneh. Kexue Fazhan Yuekan 9, 398–411.
Chen, A. H. (1982). Applied studies on the alkaloids of Phellodendron wilsonii Hay. et Kaneh. II. the alkaloid contents in Taiwan plants. Kexue Fazhan Yuekan 10, 279–286.
Chen, C., Yu, Z., Li, Y., Fichna, J., and Storr, M. (2014). Effects of berberine in the gastrointestinal tract — a review of actions and therapeutic implications. Am. J. Chin. Med. 42, 1053–1070. doi: 10.1142/S0192415X14500669
Chen, H. F., and Chen, C. M. (1988). Determination of berberine in crude and processed Chinese herb: Coptidis rhizoma and Phellodendri cortex. Zhonghua Yaoxue Zazhi 40, 259–264.
Chen, W. H., Pang, J. Y., Qin, Y., Peng, Q., Cai, Z., and Jiang, Z. H. (2005). Synthesis of linked berberine dimers and their remarkably enhanced DNA-binding affinities. Bioorg. Med. Chem. Lett. 15, 2689–2692. doi: 10.1016/j.bmcl.2004.10.098
Chen, Y., Wang, Y., Zhang, J., Sun, C., and Lopez, A. (2011). Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in association with multiple factors of insulin resistance. ISRN Endocrinol. 2011, 1–8. doi: 10.5402/2011/519371
Chen, Y. Y., Chang, F. R., and Wu, Y. C. (1996). Isoquinoline alkaloids and lignans from Rollinia mucosa. J. Nat. Prod. 59, 904–906. doi: 10.1021/np960414z
Chhetri, D. R., Parajuli, P., and Subba, G. C. (2005). Antidiabetic plants used by Sikkim and Darjeeling Himalayan tribes, India. J. Ethnopharmacol. 99, 199–202. doi: 10.1016/j.jep.2005.01.058
Chi, L., Peng, L., Pan, N., Hu, X., and Zhang, Y. (2014). The anti-atherogenic effects of berberine on foam cell formation are mediated through the upregulation of sirtuin 1. Int. J. Mol. Med. 34, 1087–1093. doi: 10.3892/ijmm.2014.1868
Chiang, Y. L., Su, C. R., Kuo, P. C., Damu, A. G., and Wu, T. S. (2006). Two isoquinolones from the roots of Phellodendron amurense var. Wilsonii. Heterocycles 68, 339–345. doi: 10.3987/COM-05-10598
Chopra, R. N., Nayar, S. I., and Chopra, I. C. (1986). Glossary of Indian Medicinal Plants (Including the Supplement). New Delhi: Canal of Scientific and Industrial Research.
Cicero, A., and Ertek, S. (2009). Berberine: metabolic and cardiovascular effects in preclinical and clinical trials. Nutr. Diet Suppl. 1, 1–10. doi: 10.2147/NDS.S6084
Coffey, T. (1993). The History and Folklore of North American Wildflowers. New York, NY: Facts on File Limited.
Dai, P., Wang, J., Lin, L., Zhang, Y., and Wang, Z. (2015). Renoprotective effects of berberine as adjuvant therapy for hypertensive patients with type 2 diabetes mellitus: evaluation via biochemical markers and color Doppler ultrasonography. Exp. Ther. Med. 10, 869–876. doi: 10.3892/etm.2015.2585
Deng, A. J., and Qin, H. L. (2010). Cytotoxic dihydrobenzophenanthridine alkaloids from the roots of Macleaya microcarpa. Phytochemistry 71, 816–822. doi: 10.1016/j.phytochem.2010.02.007
Deng, Y., Liao, Q., Li, S., Bi, K., Pan, B., and Xie, Z. (2008). Simultaneous determination of berberine, palmatine and jatrorrhizine by liquid chromatography-tandem mass spectrometry in rat plasma and its application in a pharmacokinetic study after oral administration of coptis-evodia herb couple. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 863, 195–205. doi: 10.1016/j.jchromb.2007.12.028
Dev, S. (2006). A Selection of Prime Ayurvedic Plants Drugsancient- Modern Concordance. New Delhi: Anamaya Publishers.
Din, N., Dibong, S. D., Mpondo, E. M., Priso, R. J., Kwin, N. F., and Ngoye, A. (2011). Inventory and identification of plants used in the treatment of diabetes in douala town (Cameroon). Eur. J. Med. Plants 1, 60–73. doi: 10.9734/EJMP/2011/273
Doepke, W., Ulrich, H., and Jimenez, V. (1976). On the structure of a new alkaloid from Argemone mexicana. Z. Chem. 16, 54–55.
Domitrović, R., Cvijanović, O., Pernjak-Pugel, E., Škoda, M., Mikelić, L., and Crnčević-Orlić, Ž. (2013). Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis. Food Chem. Toxicol. 62, 397–406. doi: 10.1016/j.fct.2013.09.003
Domitrović, R., Jakovac, H., and Blagojević, G. (2011). Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl4-intoxicated mice. Toxicology 280, 33–43. doi: 10.1016/j.tox.2010.11.005
Doncheva, T., Kostova, N., Yordanova, G., Saadi, H., Akrib, F., Dimitrov, D., et al. (2014). Comparison of alkaloid profile from Glaucium corniculatum (Papaveraceae) of Algerian and Bulgarian origin. Biochem. Syst. Ecol. 56, 278–280. doi: 10.1016/j.bse.2014.07.007
Du, J. X., and Wang, M. (2010). Capillary electrophoresis determination of berberine in pharmaceuticals with end-column electrochemiluminescence detection. J. Chinese Chem. Soc. 57, 696–700. doi: 10.1002/jccs.201000097
Duke, J. A., and Ayensu, E. S. (1985). Medicinal Plants of China. Algonac, MI: Reference Publications.
Duke, J. A., and Beckstrom-Sternberg, S. M. (1994). Dr. Duke's phytochemical and ethnobotanical databases. Available online at: http://www.ars-grin.gov/duke/plants.html (Accessed January 15, 2017).
Dzhalilov, D. R., Goryaev, M. I., and Kruglykhina, G. K. (1963). Alkaloids from Berberis iliensis. I Izv. Akad. Nauk Kaz. SSR, Ser. Tekhn. i Khim. Nauk 3, 15–19.
Egels, W. (1959). Papaver dubium var. lecoquii, a berberine-containing poppy. Planta Med. 7, 92–102. doi: 10.1055/s-0028-1101592
Ehiagbonare, P. O., and Onyibe, J. (2008). Conservation studies on four medicinal taxa of Southern Nigeria. Sci. Res. Essays 3, 40–45.
El Beyrouthy, M., Arnold, N., Delelis-Dusollier, A., and Dupont, F. (2008). Plants used as remedies antirheumatic and antineuralgic in the traditional medicine of Lebanon. J. Ethnopharmacol. 120, 315–334. doi: 10.1016/j.jep.2008.08.024
Emes, M., Aguilar, A., Argueta, A., and Cano, L. (1994). Indigenous Medicinal Florae from México, Vol. II.
Eric Brussell, D. (2004). A medicinal plant collection from Montserrat, West Indies. Econ. Bot. 58, S203–S220. doi: 10.1663/0013-0001(2004)58[S203:AMPCFM]2.0.CO;2
Esseily, F., El Ezzy, M., Gali-Muhtasib, H., Safi, S., Esseily, J., Diab-Assaf, M., et al. (2012). The ethanol fraction from the stem of Berberis libanotica inhibits the viability of adult T cell leukemia. Minerva Biotecnol. 24, 129–133.
Etminan, M., Gill, S. S., and Samii, A. (2005). Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis. Lancet. Neurol. 4, 362–365. doi: 10.1016/S1474-4422(05)70097-1
Fabricant, D. S., and Farnsworth, N. R. (2001). The value of plants used in traditional medicine for drug discovery. Environ. Heal. Perspect. Suppl. 109:69. doi: 10.1289/ehp.01109s169
Farías-Campomanes, A. M., Rostagno, M. A., Coaquira-Quispe, J. J., and Meireles, M. A. A. (2015). Supercritical fluid extraction of polyphenols from lees: overall extraction curve, kinetic data and composition of the extracts. Bioresour. Bioprocess. 2, 45. doi: 10.1186/s40643-015-0073-5
Feng, J., Xu, W., Tao, X., Wei, H., Cai, F., Jiang, B., et al. (2010). Simultaneous determination of baicalin, baicalein, wogonin, berberine, palmatine and jatrorrhizine in rat plasma by liquid chromatography-tandem mass spectrometry and application in pharmacokinetic studies after oral administration of traditional Chinese medicinal preparations containing Scutellaria-Coptis herb couple. J. Pharm. Biomed. Anal. 53, 591–598. doi: 10.1016/j.jpba.2010.04.002
Fletcher, M. T., Takken, G., Blaney, B. J., and Alberts, V. (1993). Isoquinoline alkaloids and keto-fatty acids of Argemone ochroleuca and A. mexicana (Mexican poppy) seed. I. An assay method and factors affecting their concentration. Aust. J. Agric. Res. 44, 265–275. doi: 10.1071/AR9930265
Fogarty, J. E. (1990). A Barefoot Doctor's Manual: The American Translation of the Official Chinese Paramedical Manual. Philadelphia, PA: Running Press Book Publishers.
Fongod, A. G. (2014). Ethnobotany, indigenous knowledge and unconscious preservation of the environment: An evaluation of indigenous knowledge in South and Southwest Regions of Cameroon. Int. J. Biodivers. Conserv. 6, 85–99. doi: 10.5897/IJBC2013.0637
Foster, S., and Duke, J. A. (1990). A Field Guide to Medicinal Plants: Eastern and Central North America. Boston, MA: Houghton Mifflin Company.
Freile, M., Giannini, F., Sortino, M., Zamora, M., Juarez, A., Zacchino, S., et al. (2006). Antifungal activity of aqueous extracts and of berberine isolated from Berberis heterophylla. Acta Farm. Bonaer. 25, 83–88.
Fyson, P. F. (1975). Flora of the Nilgiri and Pulney Hill-Tops. Dehra Dun: Bishen Singh Mahendra Pal Singh and Periodical Experts.
Gbile, Z. O., Soladoye, M. O., and Adesina, S. K. (1988). Plants in traditional medicine in West Africa. Monogr. Syst. Bot. Missouri Bot. Gard. 25, 343–349.
Gbolade, A. (2012). Ethnobotanical study of plants used in treating hypertension in Edo State of Nigeria. J. Ethnopharmacol. 144, 1–10. doi: 10.1016/j.jep.2012.07.018
Gertig, H. (1964). Alkaloids of Eschscholtzia californica. I. Isolation and thin-layer chromatography of alkaloid fractions from roots. Acta Pol. Pharm. 21, 59–64.
Gill, L. S., and Akinwumi, C. (1986). Nigerian folk medicine: practices and beliefs of the Ondo people. J. Ethnopharmacol. 18, 257–266. doi: 10.1016/0378-8741(86)90004-8
Gorval', L. M., and Grishkovets, V. I. (1999). Alkaloids of some species of the genus Berberis introduced into the Crimea. Chem. Nat. Compd. 35, 223–224. doi: 10.1007/BF02234944
Govindasamy, R., Simon, J., Puduri, V. S., Juliani, H. R., Asante-Dartey, J., Arthur, H., et al. (2007). Retailers and Wholesalers of African Herbal and Natural Products: Case Studies from Ghana and Rwanda. Issues New Crop. New Uses. Virginia ASHP, 332–337.
Greathouse, G. A. (1939). Alkaloids from Sanguinaria canadensis and their influence on growth of Phymatotrichum omnivorum. Plant Physiol. 14, 377. doi: 10.1104/pp.14.2.377
Grycová, L., Dostál, J., and Marek, R. (2007). Quaternary protoberberine alkaloids. Phytochemistry 68, 150–175. doi: 10.1016/j.phytochem.2006.10.004
Gu, Y., Zhang, Y., Shi, X., Li, X., Hong, J., Chen, J., et al. (2010). Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics. Talanta 81, 766–772. doi: 10.1016/j.talanta.2010.01.015
Guoping, L., Jinhong, L., Shuai, H., Jian, C., and Zhongyi, Z. (2012). Optimization for ultrahigh pressure extraction of berberine from Cortex phellodendri by central composite design-response surface methodology. J. Med. Plants Res. 6, 3963–3970. doi: 10.5897/JMPR11.1092
Gurguel, L., de Costa, O. A., and da Silva, R. D. (1934). Berberis laurina. Anatomic, histologic and chemical study. Bol. Assoc. Bras. pharm. 15, 11–20.
Habtemariam, S. (2011). The therapeutic potential of Berberis darwinii stem-bark: quantification of berberine and in vitro evidence for Alzheimer's disease therapy. Nat. Prod. Commun. 6, 1089–1090.
Haisova, K., and Slavik, J. (1975). On the minor alkaloids from Argemone mexicana L. Collect Czech. Chem. Commun. 40, 1576–1578. doi: 10.1135/cccc19751576
Hakim, S. A., Mijovic, V., and Walker, J. (1961). Distribution of certain poppy-fumaria alkaloids and a possible link with the incidence of glaucoma. Nature 189, 198–201. doi: 10.1038/189198a0
Hamayun, M., Khan, A., and Khan, M. A. (2003). Common medicinal folk recipes of District Buner, NWFP, Pakistan. Ethnobot. Leafl. 2003, 14.
Hamonniere, M., Leboeuf, A., and Paris, R. R. (1975). Alcaloïdes des annonacées: alcaloïdes de l'Enantia chlorantha. Plant. Med. Phytother. 9, 296–303.
Hashmi, K., and Hafiz, A. (1986). In vivo antibacterial activity of Berberis asiatica. J. Pak. Med. Assoc. 36, 5.
Hayta, S., Polat, R., and Selvi, S. (2014). Traditional uses of medicinal plants in Elazig (Turkey). J. Ethnopharmacol. 154, 613–623. doi: 10.1016/j.jep.2014.04.026
He, J.-M., and Mu, Q. (2015). The medicinal uses of the genus Mahonia in traditional Chinese medicine: an ethnopharmacological, phytochemical and pharmacological review. J. Ethnopharmacol. 175, 668–683. doi: 10.1016/j.jep.2015.09.013
Hirschhorn, H. H. (1981). Botanical remedies of South and Central America, and the Caribbean: an archival analysis. Part I. J. Ethnopharmacol. 4, 129–158. doi: 10.1016/0378-8741(81)90032-5
Houghton, P. J., and Manby, J. (1985). Medicinal plants of the Mapuche. J. Ethnopharmacol. 13, 89–103. doi: 10.1016/0378-8741(85)90063-7
Houghton, P. J., Ren, Y., and Howes, M.-J. (2006). Acetylcholinesterase inhibitors from plants and fungi. Nat. Prod. Rep. 23, 181–199. doi: 10.1039/b508966m
Hua, F., Ha, T., Ma, J., Li, Y., Kelley, J., Gao, X., et al. (2007). Protection against myocardial ischemia/reperfusion injury in TLR4-deficient mice is mediated through a phosphoinositide 3-kinase-dependent mechanism. J. Immunol. 178, 7317–7324. doi: 10.4049/jimmunol.178.11.7317
Hussain, K., Shahazad, A., and Zia-ul-Hussnain, S. (2008). An ethnobotanical survey of important wild medicinal plants of Hattar district Haripur, Pakistan. Ethnobot. Leafl. 2008, 5.
Hussaini, F. A., and Shoeb, A. (1985). Isoquinoline derived alkaloids from Berberis chitria. Phytochemistry 24, 633. doi: 10.1016/S0031-9422(00)80794-3
Hutchens, A. R. (1992). A Handbook of Native American Herbs: The Pocket Guide to 125 Medicinal Plants and Their Uses. Boston, MA: Shambhala Publications.
Imanshahidi, M., and Hosseinzadeh, H. (2008). Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phyther. Res. 22, 999–1012. doi: 10.1002/ptr.2399
Inbaraj, J. J., Kukielczak, B. M., Bilski, P., Sandvik, S. L., and Chignell, C. F. (2001). Photochemistry and photocytotoxicity of alkaloids from goldenseal (Hydrastis canadensis L.) 1. Berberine. Chem. Res. Toxicol. 14, 1529–1534. doi: 10.1021/tx0155247
Ishola, I. O., Oreagba, I. A., Adeneye, A. A., Adirije, C., Oshikoya, K. A., and Ogunleye, O. O. (2014). Ethnopharmacological survey of herbal treatment of malaria in Lagos, Southwest Nigeria. J. Herb. Med. 4, 224–234. doi: 10.1016/j.hermed.2014.08.001
Israilov, I. A., and Yunusov, S. (1986). Alkaloids of four species of Argemone. Chem. Nat. Compd. 22, 189–192. doi: 10.1007/BF00598384
Jayaprakasam, R., and Ravi, T. K. (2014). Development and validation of HPTLC and RP-HPLC methods for the estimation of berberine in Coscinium fenestratum extract and its formulation. World J. Pharm. Res. 4, 206–218.
Jha, R. N., Pandey, M. B., Singh, A. K., Singh, S., and Singh, V. P. (2009). New alkaloids from Corydalis species. Nat. Prod. Res. 23, 250–255. doi: 10.1080/14786410801996390
Jin, C., and Shan, W. (1982). Quantitative determination of berberine in Coptis chinensis by TLC scanner method. Yaoxue Tongbao 17, 145–146.
Jiofack, T., Fokunang, C., Guedje, N., and Kemeuze, V. (2009). Ethnobotany and phytomedicine of the upper Nyong valley forest in Cameroon. Afr. J. Pharm. Pharmacol. 3, 144–150.
Jiofack, T., Fokunang, C., Kemeuze, V., Fongnzossie, E., Tsabang, N., Nkuinkeu, R., et al. (2008). Ethnobotany and phytopharmacopoea of the South-West ethnoecological region of Cameroon. J. Med. Plants Res. 2, 197–206.
Joshi, A. R., and Joshi, K. (2007). Ethnomedicinal plants used against skin diseases in some villages of Kali Gandaki, Bagmati and Tadi Likhu watersheds of Nepal. Ethnobot. Leafl. 2007, 27.
Joshi, H. R., and Kanaki, N. (2013). Quantitative analysis of berberine in an ayurvedic formulation-Rasayana churna by UV spectrophotometry. J. Pharm. Sci. Biosci. Res. 3, 32–34.
Jusiak, L. (1967). Separation of Chelidonium majus alkaloids by countercurrent cascade extraction. II. Acta Pol. Pharm. 24, 65–70.
Kadiri, A. B. (2008). Evaluation of medicinal herbal trade (Paraga) in Lagos State of Nigeria. Ethnobot. Leafl. 2008, 90.
Kala, C. P. (2006). Medicinal plants of the high altitude cold desert in India: diversity, distribution and traditional uses. Int. J. Biodivers. Sci. Manage. 2, 43–56. doi: 10.1080/17451590609618098
Kamal, Y. T., Singh, M., Tamboli, E. T., Parveen, R., and Ahmad, S. (2011). Quantitative analysis of berberine in Berberis aristata fruits and in a traditional anti-inflammatory unani formulation by use of a validated HPLC method. Acta Chromatogr. 23, 157–168. doi: 10.1556/AChrom.21.2013.1.11
Kamigauchi, M., and Iwasa, K. (1994). “Corydalis spp.: in vitro culture and the biotransformation of protoberberines,” in Medicinal and Aromatic Plants VI. Biotechnology in Agriculture and Forestry, Vol 26, ed Y. P. S. Bajaj (Berlin; Heidelberg: Springer), 93–105.
Karimov, A., and Lutfullin, K. L. (1986). Berberis alkaloids. 2'-N-methylisotetrandrine from Berberis oblonga. Khimiya Prir. Soedin. 2, 249–251.
Karimov, A., Meliboev, S., Olimov, V., and Shakirov, R. (1993). Berberis alkaloids. XXX. Dynamics of alkaloid accumulation in Berberis integerrima and B. nummularia. Khimiya Prir. Soedin. 3, 472–473.
Karimov, A., and Shakirov, R. (1993). Berberis alkaloids. XX. Alkaloids of Berberis iliensis. Khimiya Prir. Soedin. 1, 83–84. doi: 10.1007/BF00631020
Kataoka, M., Tokuyama, E., Miyanaga, Y., and Uchida, T. (2008). The taste sensory evaluation of medicinal plants and Chinese medicines. Int. J. Pharm. 351, 36–44. doi: 10.1016/j.ijpharm.2007.09.017
Kaur, C., and Miani, S. (2001). Fruits and vegetables healthy foods for new millennium. Indian Hort. 45, 29–32.
Kayode, J. (2006). Conservation of indigenous medicinal botanicals in Ekiti State, Nigeria. J. Zhejiang Univ. Sci. B 7, 713–718. doi: 10.1631/jzus.2006.B0713
Khalmatov, K. (1964). Khalmatov, Wild-Growing Medicinal Plants of Uzbekistan [in Russian] Tashkent. Meditsina.
Khamidov, I., Faskhutdinov, M., Telezhenetskaya, M. V., Karimov, A., Levkovich, M. G., Abdullaev, N. D., et al. (1996a). Berberis alkaloids. XXXIV. Turcomanine, a new alkaloid from Berberis turcomanica. Khimiya Prir. Soedin. 1, 74–76.
Khamidov, I., Karimov, A. K., Telezhenetskaya, M. V., and Tashkhodzhaev, B. (1996b). Berberis alkaloids. XXXV. Berberis turcomanica. Khimiya Prir. Soedin. 1, 107–109.
Khamidov, I. I., Aripova, S. F., Karimov, A., and Yusupov, M. M. (1997a). Berberis alkaloids. XL. An investigation of the alkaloids of Berberis thunbergii. Chem. Nat. Compd. 33, 599–599. doi: 10.1007/BF02254817
Khamidov, I. I., Aripova, S. F., and Karimov, A. K. (2003). Berberis alkaloids. XLI. Alkaloids from leaves of cultivated Berberis oblonga. Chem. Nat. Compd. 39, 407. doi: 10.1023/B:CONC.0000003429.41497.b6
Khamidov, I. I., Aripova, S. F., Telezhenetskaya, M. V., Karimov, A., and Dzhenberov, I. (1997b). Berberis alkaloids XXXIX. New alkaloids from B. densiflora. Chem. Nat. Comp. 33, 323–325. doi: 10.1007/BF02234886
Khamidov, I. I., Tashkhodzhaev, B., Aripova, S. F., Telezhenetskaya, M. V., and Karimov, A. K. (1996c). Berberis alkaloids. XXXVII. Study of the alkaloids of B. oblonga and B. integerrima. Crystal structure of 8-trichloromethyldihydroberberine. Khimiya Prir. Soedin. 6, 889–893.
Khan, I., Najeebullah, S., Ali, M., and Shinwari, Z. K. (2016). Phytopharmacological and ethnomedicinal uses of the Genus Berberis (Berberidaceae): a review. Trop. J. Pharm. Res. 15, 2047–2057. doi: 10.4314/tjpr.v15i9.33
Khan, M. I., Sri Harsha, P. S. C., Giridhar, P., and Ravishankar, G. A. (2011). Berberine and lycopene profiling during the ontogeny of Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms fruit. Curr. Sci. 100, 1225–1231.
Khan, S. W., and Khatoon, S. (2007). Ethnobotanical studies on useful trees and shrubs of Haramosh and Bugrote valleys in Gilgit northern areas of Pakistan. Pak. J. Bot. 39, 699–710.
Khodzhimatov, M. (1989). Dikorastushchiye Lekarstvennuiye Rasteniya Tadzhikistana [Wild-Growing Medicinal Plants of Tadjikistan].
Kirtikar, K. R., and Basu, B. D. (1998). Indian Medicinal Plants, Vol 1. Allahabad: CSIR publication.
Kiryakov, H. G., Daskalova, E., Georgieva, A., Kuzmanov, B., and Evstatieva, L. (1982a). Alkaloids from Corydalis solida (L.) Swarz. Folia Med. 24, 19–22.
Kiryakov, H. G., Iskrenova, E., Daskalova, E., Kuzmanov, B., and Evstatieva, L. (1982b). Alkaloids of Corydalis slivenensis. Planta Med. 44, 168–170. doi: 10.1055/s-2007-971432
Knapp, J. E., Hussein, F. T., Beal, J. L., Doskotch, R. W., and Tomimatsu, T. (1967). Isolation of two bisbenzylisoquinoline alkaloids from the rhizomes and roots of Xanthorhiza simplicissima. J. Pharm. Sci. 56, 139–141. doi: 10.1002/jps.2600560129
Končić, M. Z., Kremer, D., Schühly, W., Brantner, A., Karlović, K., and Kalodera, Z. (2010). Chemical differentiation of Berberis croatica and B. vulgaris using HPLC fingerprinting. Croat. Chem. Acta 83, 451–456.
Kong, W. J., Wei, J., Zuo, Z. Y., Wang, Y. M., Song, D. Q., You, X. F., et al. (2008). Combination of simvastatin with berberine improves the lipid-lowering efficacy. Metabolism. 57, 1029–1037. doi: 10.1016/j.metabol.2008.01.037
Kong, Y., Xiao, J.-J., Meng, S.-C., Dong, X.-M., Ge, Y.-W., Wang, R.-F., et al. (2010). A new cytotoxic flavonoid from the fruit of Sinopodophyllum hexandrum. Fitoterapia 81, 367–370. doi: 10.1016/j.fitote.2009.11.003
Kosalec, I., Gregurek, B., Kremer, D., Zovko, M., Sanković, K., and Karlović, K. (2009). Croatian barberry (Berberis croatica Horvat): a new source of berberine? analysis and antimicrobial activity. World J. Microbiol. Biotechnol. 25, 145–150. doi: 10.1007/s11274-008-9860-x
Kosina, P., Gregorova, J., Gruz, J., Vacek, J., Kolar, M., Vogel, M., et al. (2010). Phytochemical and antimicrobial characterization of Macleaya cordata herb. Fitoterapia 81, 1006–1012. doi: 10.1016/j.fitote.2010.06.020
Kostalova, D., Brazdovicova, B., and Jin, H. Y. (1982). Alkaloids from the aboveground parts of Berberis koreana Palib. Farm. Obz. 51, 213–216.
Kubota, M., Katsunori, M., and Miyazawa, Y. (1980). Berberine contents in cultivated Coptis japonica Makino. Nagano-ken Eisei Kogai Kenkyusho Kenkyu Hokoku 2, 22–27.
Kukula-Koch, W., and Mroczek, T. (2015). Application of hydrostatic CCC–TLC–HPLC–ESI-TOF-MS for the bioguided fractionation of anticholinesterase alkaloids from Argemone mexicana L. roots. Anal. Bioanal. Chem. 407, 2581–2589. doi: 10.1007/s00216-015-8468-x
Kulkarni, S. K., and Dhir, A. (2010). Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders. Phyther. Res. 24, 317–324. doi: 10.1002/ptr.2968
Kunwar, R. M., and Adhikari, N. (2005). Ethnomedicine of Dolpa district, Nepal: the plants, their vernacular names and uses. Lyonia 8, 43–49. doi: 10.1186/1746-4269-2-27
Küpeli, E., Koşar, M., Yeşilada, E., Hüsnü, K., and Başer, C. (2002). A comparative study on the anti-inflammatory, antinociceptive and antipyretic effects of isoquinoline alkaloids from the roots of Turkish Berberis species. Life Sci. 72, 645–657. doi: 10.1016/S0024-3205(02)02200-2
Ladino, O. J. P., and Suárez, L. E. C. (2010). Chemical constituents of the wood from Zanthoxylum quinduense Tul. (Rutaceae). Quim. Nova 33, 1019–1021. doi: 10.1590/S0100-40422010000500002
Lee, H. Y., and Kim, C. W. (1999). Isolation and quantitative determination of berberine and coptisine from tubers of Corydalis ternata. Saengyak Hakhoechi 30, 332–334.
Leone, M. G., Cometa, M. F., Palmery, M., and Saso, L. (1996). HPLC determination of the major alkaloids extracted from Hydrastis canadensis L. Phyther. Res. 10, S45–S46.
Li, H., Li, X. L., Zhang, M., Xu, H., Wang, C. C., Wang, S., et al. (2014). Berberine ameliorates experimental autoimmune neuritis by suppressing both cellular and humoral immunity. Scand. J. Immunol. 79, 12–19. doi: 10.1111/sji.12123
Li, W. L., Zheng, H. C., Bukuru, J., and De Kimpe, N. (2004). Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus. J. Ethnopharmacol. 92, 1–21. doi: 10.1016/j.jep.2003.12.031
Li, Y.-H., Zhang, M., Xiao, H.-T., Fu, H.-B., Ho, A., Lin, C.-Y., et al. (2015). Addition of berberine to 5-aminosalicylic acid for treatment of dextran sulfate sodium-induced chronic colitis in C57BL/6 Mice. PLoS ONE 10:e0144101. doi: 10.1371/journal.pone.0144101
Liu, B., Li, W., Chang, Y., Dong, W., and Ni, L. (2006). Extraction of berberine from rhizome of Coptis chinensis Franch using supercritical fluid extraction. J. Pharm. Biomed. Anal. 41, 1056–1060. doi: 10.1016/j.jpba.2006.01.034
Liu, F., Li, Z., Shi, X., and Zhong, M. (2011). Determination of berberine, palmatine and jatrorrhizine in rabbit plasma by liquid chromatography-electrospray ionization-mass spectrometry. J. Pharm. Biomed. Anal. 56, 1006–1015. doi: 10.1016/j.jpba.2011.08.001
Liu, L., Liu, J., Huang, Z., Yu, X., Zhang, X., Dou, D., et al. (2015). Berberine improves endothelial function by inhibiting endoplasmic reticulum stress in the carotid arteries of spontaneously hypertensive rats. Biochem. Biophys. Res. Commun. 458, 796–801. doi: 10.1016/j.bbrc.2015.02.028
Liu, L., Wang, Z. B., Song, Y., Yang, J., Wu, L. J., Yang, B. Y., et al. (2016). Simultaneous determination of eight alkaloids in rat plasma by UHPLC-MS/MS after oral administration of Coptis deltoidea C.Y. Cheng et Hsiao and Coptis chinensis Franch. Molecules 21, 1–15.
Liu, M., Su, X., Li, G., Zhao, G., and Zhao, L. (2015). Validated UPLC-MS/MS method for simultaneous determination of simvastatin, simvastatin hydroxy acid and berberine in rat plasma: application to the drug-drug pharmacokinetic interaction study of simvastatin combined with berberine after oral administratio. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 1006, 8–15. doi: 10.1016/j.jchromb.2015.09.033
Liu, S., Chen, Y., Gu, L., Li, Y., Wang, B., Hao, J., et al. (2013). Effects of ultrahigh pressure extraction conditions on yields of berberine and palmatine from Cortex phellodendri amurensis. Anal. Methods 5, 4506. doi: 10.1039/c3ay40784e
Liu, W., Liu, P., Tao, S., Deng, Y., Li, X., Lan, T., et al. (2008b). Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose. Arch. Biochem. Biophys. 475, 128–134. doi: 10.1016/j.abb.2008.04.022
Liu, W. H., Hei, Z. Q., Nie, H., Tang, F. T., Huang, H. Q., Li, X. J., et al. (2008a). Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase. Chin. Med. J. 121, 706–712.
Liu, X., Zhang, X., Ye, L., and Yuan, H. (2016). Protective mechanisms of berberine against experimental autoimmune myocarditis in a rat model. Biomed. Pharmacother. 79, 222–230. doi: 10.1016/j.biopha.2016.02.015
Lou, Y., Yuming, W., Yanfen, D., Jida, S., and Huang, L. (1982). Extractive spectrophotometric determination of berberine. Yaowu Fenxi Zazhi 2, 82–85.
Lust, J. (2014). The Herb Book: The Most Complete Catalog of Herbs Ever Published. New York, NY: Courier Corporation.
Ma, X., Jiang, Y., Wu, A., Chen, X., Pi, R., Liu, M., et al. (2010). Berberine attenuates experimental autoimmune encephalomyelitis in C57 BL/6 mice. PLoS ONE 5:e13489. doi: 10.1371/journal.pone.0013489
Maithani, A., Parcha, V., and Kumar, D. (2014). Quantitative estimation of berberine content of Berberis asiatica from different altitude of Garhwal Himalaya. Asian J. Pharm. Clin. Res. 7, 165–167.
Majumder, B., Schindra, S. N., and Dutta, P. C. (1956). Occurrence of ceryl alcohol in Argemone mexicana. J. Indian Chem. Soc. 33, 351–352.
Manske, R. H. F. (1939). The alkaloids of fumariaceous plants. XIX. Corydalis ophiocarpa Hook. f. et Thoms. Can. J. Res. Sect. B Chem. Sci. 17, 51–56. doi: 10.1139/cjr39b-009
Marek, R., Seckárová, P., Hulová, D., Marek, J., Dostál, J., and Sklenár, V. (2003). Palmatine and berberine isolation artifacts. J. Nat. Prod. 66, 481–486. doi: 10.1021/np0204996
Martinez, M. (1984). Las Plantas Medicinales De México, 3rd Edn. Mexico City: CIESAS, Cuadernos de la Casa Chata.
Mascareno, E., El-Shafei, M., Maulik, N., Sato, M., Guo, Y., Das, D. K., et al. (2001). JAK/STAT signaling is associated with cardiac dysfunction during ischemia and reperfusion. Circulation 104, 325–329. doi: 10.1161/01.CIR.104.3.325
Meena, A. K., Bansal, P., and Kumar, S. (2009). Plants-herbal wealth as a potential source of ayurvedic drugs. Asian J. Tradit. Med. 4, 152–170.
Mikage, M., and Mouri, C. (1999). Pharmacognostical studies of Berberis plants (Berberidaceae) from Nepal (1). Altitudinal, interspecific, and partial variations of berberine content in the barks. Sect. Title Pharm. 53, 249–254.
Mills, S. (1985). The Dictionary of Modern Herbalism: A Comprehensive Guide to Practical Herbal Therapy. Wellingborough: Inner Traditions/Bear & Co.
Minaiyan, M., Ghannadi, A., Mahzouni, P., and Jaffari-Shirazi, E. (2011). Comparative study of Berberis vulgaris fruit extract and berberine chloride effects on acetic acid-induced colitis in rats. Iran. J. Pharm. Res. 10, 97–104.
Misra, P. S., Bhakuni, D. S., Sharma, V. N., and Kaul, K. N. (1961). Chemical constituents of Argemone mexicana. J. Sci. Ind. Res. 20, 186.
Mokgadi, J., Turner, C., and Torto, N. (2013). Pressurized hot water extraction of alkaloids in Goldenseal. Am. J. Anal. Chem. 4, 398–403. doi: 10.4236/ajac.2013.48050
Mølgaard, P., Holler, J. G., Asar, B., Liberna, I., Rosenbæk, L. B., Jebjerg, C. P., et al. (2011). Antimicrobial evaluation of Huilliche plant medicine used to treat wounds. J. Ethnopharmacol. 138, 219–227. doi: 10.1016/j.jep.2011.09.006
Monforte-Gonzalez, M., Cecilia, G. G., Jorge, R. P., Mildred, C. P., and Vazquez-Flota, F. (2012). Berberine and sanguinarine quantitation in Argemone mexicana L. (Papaveraceae) tissues by TLC-in situ fluorography. J. Planar Chromatogr. TLC 24, 358–360. doi: 10.1556/JPC.25.2012.4.14
Montes, M., and Wilkomirsky, T. (1987). Medicina Tradicional Chilena. Concepción: Editiorial de la Universidad de Concepción.
Muñoz, O. (2001). Plantas Medicinales de uso en Chile: Química y Farmacología. Editorial Universitaria.
Mustafa, A., and Turner, C. (2011). Pressurized liquid extraction as a green approach in food and herbal plants extraction: a review. Anal. Chim. Acta 703, 8–18. doi: 10.1016/j.aca.2011.07.018
Musumeci, R., Speciale, A., Costanzo, R., Annino, A., Ragusa, S., Rapisarda, A., et al. (2003). Berberis aetnensis C. Presl. extracts: antimicrobial properties and interaction with ciprofloxacin. Int. J. Antimicrob. Agents 22, 48–53. doi: 10.1016/S0924-8579(03)00085-2
Musuyu Muganza, D., Fruth, B. I., Nzunzu Lami, J., Mesia, G. K., Kambu, O. K., Tona, G. L., et al. (2012). In vitro antiprotozoal and cytotoxic activity of 33 ethonopharmacologically selected medicinal plants from Democratic Republic of Congo. J. Ethnopharmacol. 141, 301–308. doi: 10.1016/j.jep.2012.02.035
Ndenecho, E. N. (2009). Herbalism and resources for the development of ethnopharmacology in Mount Cameroon region. Afr. J. Pharm. Pharmacol. 3, 78–86.
Neuwinger, H. D. (1996). African Ethnobotany: Poisons and Drugs: Chemistry, Pharmacology, Toxicology. London: CRC Press.
Ngono Ngane, R., Koanga Mogtomo, M., Tchinda Tiabou, A., Magnifouet Nana, H., Motso Chieffo, P. R., Mballa Bounou, Z., et al. (2011). Ethnobotanical survey of some Cameroonian plants used for treatment of viral diseases. Afr. J. Plant Sci. 5, 15–21.
Nguimatsia, F., Boustie, J., Baril, F., Amoros, M., and Girre, L. (1998). Les medicaments des pygmees Baka du Cameroun: moeurs therapeutiques, maladies et inventaire des plantes medicinales. Fitoterapia 69, 29–40.
Noumi, E. (2010). Ethno medicines used for treatment of prostatic disease in Foumban, Cameroon. Afr. J. Pharm. Pharmacol. 4, 793–805.
Noumi, E., and Anguessin, B. (2010). Insecticides and ethnomedicine of HIV/AIDS at Tokombere (Far North Cameroon). Int. J. Pharm. Biomed. Sci. 2, 20–28.
Noumi, E., and Yumdinguetmun, R. (2010). Plants and treatment of prostatic diseases in Foumban (West Region, Cameroon). Syllab. Rev. 2, 9–16.
Odugbemi, T. O., Akinsulire, O. R., Aibinu, I. E., and Fabeku, P. O. (2007). Medicinal plants useful for malaria therapy in Okeigbo, Ondo State, Southwest Nigeria. Afr. J. Tradit. Complement. Altern. Med. 4, 191–198.
Ogbonna, D. N., Sokari, T. G., and Agomuoh, A. A. (2008). Antimalarial activities of some selected traditional herbs from Southeastern Nigeria against Plasmodium species. Res. J. Parasitol. 3, 25–31. doi: 10.3923/jp.2008.25.31
Ohemu, T. L., Agunu, A., Olotu, P. N., Ajima, U., Dafam, D. G., and Azila, J. J. (2014). Ethnobotanical survey of medical plants used in the traditional treatment of viral infections in Jos, plateau state, Nigeria. Int. J. Med. Aromat. Plants 4, 74–81.
Okunade, A. L., Hufford, C. D., Richardson, M. D., Peterson, J. R., and Clar, A. M. (1994). Antimicrobial Properties of Alkaloids from Xanthorhiza simplicissima. J. Pharm. Sci. 83, 404–406. doi: 10.1002/jps.2600830327
Oladunmoye, M. K., and Kehinde, F. Y. (2011). Ethnobotanical survey of medicinal plants used in treating viral infections among Yoruba tribe of South Western Nigeria. Afr. J. Microbiol. Res. 5, 2991–3004. doi: 10.5897/AJMR10.004
Oliver, B. E. P. (1960). Medicinal Plants in Nigeria: Being a Course of Four Lectures. Pharmacy Department of the Nigerian College of Arts, Science and Technology, Ibadan.
Olowokudejo, J. D., Kadiri, A. B., and Travih, V. A. (2008). An ethnobotanical survey of herbal markets and medicinal plants in Lagos State of Nigeria. Ethnobot. Leafl. 2008, 116.
Onwuanibe, R. C. (1979). The philosophy of African medical practice. Afr. Issues 9, 25–28. doi: 10.2307/1166259
Orhan, I., Sener, B., Choudhary, M. I., and Khalid, A. (2004). Acetylcholinesterase and butyrylcholinesterase inhibitory activity of some Turkish medicinal plants. J. Ethnopharmacol. 91, 57–60. doi: 10.1016/j.jep.2003.11.016
Othman, M. S., Safwat, G., Aboulkhair, M., and Abdel Moneim, A. E. (2014). The potential effect of berberine in mercury-induced hepatorenal toxicity in albino rats. Food Chem. Toxicol. 69, 175–181. doi: 10.1016/j.fct.2014.04.012
Pak, V. (2005). Medicine plants of folk medicine used for treatment of gastro-intestinal problems in Fergana valley. Korean Food Res. Inst. 18, 150–157.
Pant, N., Garg, H. S., and Bhakuni, K. (1986). Chemical constituents of B. pseudoumbellata. Fitoterapia 51, 427–428.
Park, D. W., Jiang, S., Liu, Y., Siegal, G. P., Inoki, K., Abraham, E., et al. (2014). GSK3β-Dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury. Am. J. Physiol. 307, L735–L745. doi: 10.1152/ajplung.00165.2014
Park, J.-I., Shim, J.-K., Do, J.-W., Kim, S.-Y., Seo, E.-K., Kwon, H.-J., et al. (1999). Immune-stimulating properties of polysaccharides from Phellodendri cortex (Hwangbek). Glycoconj. J. 16, 247–252. doi: 10.1023/A:1007084506071
Parsons, H. B. (1882). Examination of the root of Berberis aquifolium, v. alpens, “oregon grape root.” Pharm. J. 13, 46–48.
Patel, M. C. (2013). Isolation of berberine from Berberis aristata by an acid dye method and optimization of parameters. Int. J. Pharm. Sci. Rev. Res. 20, 187–189.
Pathak, N. K. R., Biswas, M., Seth, K. K., Dwivedi, S. P. D., and Pandey, V. B. (1985). Chemical investigation of Argemone mexicana. Pharmazie 40, 202.
Pěnčíková, K., Urbanová, J., Musil, P., Táborská, E., and Gregorová, J. (2011). Seasonal Variation of Bioactive Alkaloid Contents in Macleaya microcarpa (Maxim.) Fedde. Molecules 16, 3391–3401. doi: 10.3390/molecules16043391
Perkin, A. G., and Hummel, J. J. (1895). XLV.—The colouring principle of Toddalia aculeata and Evodia meliaefolia. J. Chem. Soc. Trans. 67, 413–416. doi: 10.1039/CT8956700413
Petcu, P. (1965a). Der gehalt an alkaloiden und vitamin C in Berberis guimpelii. Planta Med. 13, 178–181. doi: 10.1055/s-0028-1100108
Petcu, P. (1965b). Phytochemical investigation of Berberis koreana. Farm. Bucharest, Rom. 13, 21–28.
Pfoze, N. L., Myrboh, B., Kumar, Y., and Rohman, R. (2014). Isolation of protoberberine alkaloids from stem bark of Mahonia manipurensis Takeda using RP-HPLC. J. Med. Plants Stud. 2, 48–57.
Phillipson, J. D., Gray, A. I., Askari, A. A. R., and Khalil, A. A. (1981). Alkaloids From Iraqi Species of Papaveraceae. J. Nat. Prod. 44, 296–307. doi: 10.1021/np50015a011
Phondani, P. C., Maikhuri, R. K., Rawat, L. S., Farooquee, N. A., Kala, C. P., Vishvakarma, S. C. R., et al. (2010). Ethnobotanical uses of plants among the Bhotiya tribal communities of Niti Valley in Central Himalaya, India. Ethnobot. Res. Appl. 8, 233–244. doi: 10.17348/era.8.0.233-244
Pilch, W., Szygula, Z., Tyka, A. K., Palka, T., Tyka, A., Cison, T., et al. (2014). Disturbances in pro-oxidant-antioxidant balance after passive body overheating and after exercise in elevated ambient temperatures in athletes and untrained men. PLoS ONE 9:e85320. doi: 10.1371/journal.pone.0085320
Rahal, A., Kumar, A., Singh, V., Yadav, B., Tiwari, R., Chakraborty, S., et al. (2014). Oxidative stress, prooxidants, and antioxidants: The interplay. Biomed Res. Int. (2014). doi: 10.1155/2014/761264
Rajasekaran, A., and Kumar, N. (2009). Rasont – A traditional crude drug prepared from Berberis sp and its uses. Indian, J. Tradit. Knowl. 8, 562–563.
Ransohoff, R. M., Hafler, D. A., and Lucchinetti, C. F. (2015). Multiple sclerosis — a quiet revolution. Nat. Rev. Neurol. 11, 134–142. doi: 10.1038/nrneurol.2015.14
Rashid, M. H., and Malik, M. N. (1972). Composition of alkaloids in some Berberis species. Pakistan J. For. 22, 43–47.
Rashmi, R. A., Pokhriyal, R., and Singh, Y. (2009). Quantitative Estimation of Berberine in Roots of Different provenances of Berberis aristata DC by HPLC and Study of their Antifungal Properties. Pharmacogn. Mag. 5, 355–358. doi: 10.4103/0973-1296.58566
Richert, F. (1918). The extraction of berberine from “michai” (Berberis darwinii) and “calafate” (B. vuxifolia), in the Argentine. Rev. del Cent. Estud. Agron. y Vet. la Univ. Buenos Aires 11, 11–13.
Ritch-Krc, E. M., Thomas, S., Turner, N. J., and Towers, G. H. N. (1996). Carrier herbal medicine: traditional and contemporary plant use. J. Ethnopharmacol. 52, 85–94. doi: 10.1016/0378-8741(96)01392-X
Rivera Núñez, D., and Obon de Castro, C. (1996). Ethnopharmacology of Murcia, Actes du 2a Colloque Européen d'Ethnopharmacologei et de la 11a Conférence internationale d'Ethnomédecine (Heidelberg), 24.
Rojsanga, P., and Gritsanapan, W. (2005). Variation of Berberine Content in Coscinium fenestratum Stem in Thailand Market. Mahidol Univ. J. Pharm. Sci. 32, 66–70.
Rojsanga, P., Gritsanapan, W., and Suntornsuk, L. (2006). Determination of berberine content in the stem extracts of Coscinium fenestratum by TLC densitometry. Med. Princ. Pract. 15, 373–378. doi: 10.1159/000094272
Samal, P. K. (2013). HPTLC analysis of berberine in Argemone mexicana, L. J. Glob. Trends Pharm. Sci. 4, 1073–1076.
Samhita, S. (1963). Sutrasthanam Lakshadi Group. Ed K. K. Bhishagratna. Varanasi: Chaukhamba Sanskrit Sansthan.
San Martín, J. (1983). Medicinal plants in central Chile. Econ. Bot. 37, 216–227. doi: 10.1007/BF02858788
Sandberg, F. (1965). Etude sur les plantes medicinales et toxiques d'Afrique equatoriale. 1. Premier inventaire des plantes medicinales et toxiques de la region sudouest de la Republique Centrafricaine et de la region nord de la Republique du Congo/Brazzaville. Cah. la Maboké 3, 5–49.
Santos, A. C., and Adkilen, P. (1932). The alkaloids of Argemone mexicana. J. Am. Chem. Soc. 54, 2923–2924. doi: 10.1021/ja01346a037
Santra, D. K., and Saoji, A. N. (1971). Phytochemical study of Argemone mexicana latex. Curr. Sci. 40, 548–549.
Saraf, G., Mitra, A., Kumar, D., Mukherjee, S., and Basu, A. (2010). Role of nonconventional remedies in rural India. Int. J. Pharm. Life Sci. 1, 141–159.
Sasidharan, S., Chen, Y., Saravanan, D., Sundram, K. M., and Yoga Latha, L. (2011). Extraction, isolation and characterization of bioactive compounds from plants' extracts. Afr. J. Tradit. Complement. Altern. Med. 8, 1–10.
Sati, S. C., and Joshi, S. (2011). Aspects of antifungal potential of ethnobotanically known medicinal plants. Res. J. Med. Plants 5, 377–391. doi: 10.3923/rjmp.2011.377.391
Satija, S., Bansal, P., Dureja, H., and Garg, M. (2015). Microwave assisted extraction of Tinospora cordifolia and optimization through central composite design. J. Biol. Sci. 15, 106–115. doi: 10.3923/jbs.2015.106.115
Sato, F., and Yamada, Y. (1984). High berberine-producing cultures of Coptis japonica cells. Phytochemistry 23, 281–285. doi: 10.1016/S0031-9422(00)80318-0
Satyavati, G. V., Raina, M. K., and Sharma, M. (1987). Medicinal plants of India. New Delhi: Indian Council of Medical Research.
Schieffer, G. W., and Pfeiffer, K. (2001). Pressurized liquid extraction and multiple, ultrasonically-assisted extraction of hydrastine and berberine from Goldenseal (Hydrastis canadensis) with susequent HPLC assay. J. Liq. Chromatogr. Relat. Technol. 24, 2415–2427. doi: 10.1081/JLC-100105948
Schlotterbeck, J. O. (1902). Does Argemone mexicana contain morphine? J. Am. Chem. Soc. 24, 238–242. doi: 10.1021/ja02017a006
Seino, Y., Fukushima, M., and Yabe, D. (2010). GIP and GLP-1, the two incretin hormones: similarities and differences. J. Diabetes Investig. 1, 8–23. doi: 10.1111/j.2040-1124.2010.00022.x
Sener, B., and Temizer, H. (1988). Pharmacognosic investigations on Corydalis solida (L.) Swartz ssp. brachyloba (Boiss.) Cullen & Davis. II. Alkaloids of Corydalis solida (L.) Swartz ssp. brachyloba (Boiss.) Cullen & Davis. Gazi Univ. Eczac. Fak. Derg. 5, 9–11.
Sener, B., and Temizer, H. (1990). Chemical Studies on the Alkaloids from Corydalis solida subsp. tauricola. Planta Med. 56, 510–510. doi: 10.1055/s-2006-961052
Sener, B., and Temizer, H. (1991). Chemical studies on the minor isoquinoline alkaloids from Corydalis solida subsp. brachyloba. J. Chem. Soc. Pakistan 13, 63–66.
Sezik, E., Yesilada, E., Shadidoyatov, H., Kulivey, Z., Nigmatullaev, A. M., Aripov, H. N., et al. (2004). Folk medicine in Uzbekistan: I. Toshkent, Djizzax, and Samarqand provinces. J. Ethnopharmacol. 92, 197–207. doi: 10.1016/j.jep.2004.02.016
Shah, G. M., and Khan, M. A. (2006). Common medicinal folk recipes of Siran valley, Mansehra, Pakistan. Ethnobot. Leafl. 2006, 5.
Shahid, M., Rahim, T., Shahzad, A., Latif, T. A., Fatma, T., Rashid, M., et al. (2009). Ethnobotanical studies on Berberis aristata DC. root extracts. African, J. Biotechnol. 8, 556–563.
Sharma, P. K., Chauhan, N. S., and Lal, B. (2005). Studies on plant associated indigenous knowledge among Malanis of Kullu district, Himachal Pradesh. Indian J. Trad. Knowl. 4, 403–408.
Shigwan, H., Saklani, A., Hamrapurkar, P. D., Mane, T., and Bhatt, P. (2013). HPLC method development and validation for quantification of berberine from Berberis aristata and Berberis tinctoria. Int. J. Appl. Sci. Eng. 11, 203–211.
Shirwaikar, A., Shirwaikar, A., Rajendran, K., and Punitha, I. S. R. (2006). In vitro antioxidant studies on the benzyl tetra isoquinoline alkaloid berberine. Biol. Pharm. Bull. 29, 1906–1910. doi: 10.1248/bpb.29.1906
Singh, A., Duggal, S., Kaur, N., and Singh, J. (2010). Berberine: Alkaloid with wide spectrum of pharmacological activities. J. Nat. Prod. 3, 64–75.
Singh, A., Lal, M., and Samant, S. S. (2009). Diversity, indigenous uses and conservation prioritization of medicinal plants in Lahaul valley, proposed Cold Desert Biosphere Reserve, India. Int. J. Biodivers. Sci. Manag. 5, 132–154. doi: 10.1080/17451590903230249
Singh, I. P., and Mahajan, S. (2013). Berberine and its derivatives: a patent review (2009-2012). Expert Opin. Ther. Pat. 23, 215–231. doi: 10.1517/13543776.2013.746314
Singh, J., and Kakkar, P. (2009). Antihyperglycemic and antioxidant effect of Berberis aristata root extract and its role in regulating carbohydrate metabolism in diabetic rats. J. Ethnopharmacol. 123, 22–26. doi: 10.1016/j.jep.2009.02.038
Singh, R., Katiyar, C., and Pasrija, A. (2010). Validated HPLC-UV method for the determination of berberine in raw herb Daruharidra (Berberis aristata DC), its extract, and in commercially marketed ayurvedic dosage forms. Int. J. Ayurveda Res. 1, 243. doi: 10.4103/0974-7788.76789
Singh, R., Tiwari, S. S., Srivastava, S., and Rawat, A. K. S. (2012). Botanical and phytochemical studies on roots of Berberis umbellata Wall. ex G. Don. Indian J. Nat. Prod. Resour. 3, 55–60.
Singh, S. (2014). Quantitative analysis of Berberine in Argemone mexicana Linn. (Papaveraceae) using HPLC and HPTLC. Adv. Plant Sci. 27, 209–211.
Singh, S. S., Pandey, S. C., Srivastava, S., Gupta, V. S., Patro, B., and Ghosh, A. C. (2003). Chemistry and medicinal properties of Tinospora cordifolia (Guduchi). Indian J. Pharmacol. 35, 83–91.
Sir, C. C., and Chopra, I. C. (1958). Indigenous Drugs of India. Kolkata: U.N.Dhar and Sons Private Limted.
Slavík, J. (1978). Characterization of alkaloids from the roots of Papaver rhoeas L. Collect. Czechoslov. Chem. Commun. 43, 316–319. doi: 10.1135/cccc19780316
Slavik, J., and Slavikova, L. (1957). Alkaloide der mohngewächse (Papaveraceae) VIII. Die alkaloide des roten hornmohns (Glaucium corniculatum CURT.). Collect. Czechoslov. Chem. Commun. 22, 279–285. doi: 10.1135/cccc19570279
Slavik, J., and Slavikova, L. (1975). Alkaloids of Papaveraceae. LIX. Alkaloids from the leaves of Bocconia frutescens. Collect. Czechoslov. Chem. Commun. 40, 3206–3210. doi: 10.1135/cccc19753206
Slavik, J., Slavikova, L., and Bochorakova, J. (1989). Alkaloids of the Papaveraceae. Part LXXXVIII. Alkaloids from Papaver rhoeas var. chelidonioides O. Kuntze, P. confine Jord., and P. dubium L. Collect. Czechoslov. Chem. Commun. 54, 1118–1125. doi: 10.1135/cccc19891118
Slavikova, L., and Slavik, J. (1955). Alkaloids of Papaveraceae. VII. Argemone mexicana. Chem. List. Pro Vedu a Prum. 49, 1546–1549.
Slavikova, L., and Slavik, J. (1966). Alkaloide der mohngewächse (Papaveraceae) XXXII. Über die alkaloide aus Hunnemannia fumariaefolia SWEET und über die konstitution des alkaloids HF 1. Collect. Czechoslov. Chem. Commun. 31, 1355–1362. doi: 10.1135/cccc19661355
Slavikova, L., Tschu, S., and Slavik, J. (1960). Alkaloids of Papaveraceae. XIV. Alkaloids of Argemone alba. Collect. Czechoslov. Chem. Commun. 25, 756–760. doi: 10.1135/cccc19600756
Smyth, B. B. (1903). Preliminary list of medicinal and economic kansas plants, with their reputed therapeutic properties. Trans. Kansas Acad. Sci. 18, 191–209. doi: 10.2307/3624794
Sood, P., Modgil, R., and Sood, M. (2010). Physico-chemical and nutritional evaluation of indigenous wild fruit Kasmal, Berberis lycium Royle. Indian J. Nat. Prod. Resour. 1, 362–366.
Srinivasan, G. V., Unnikrishnan, K. P., Rema Shree, A. B., and Balachandran, I. (2008). HPLC estimation of berberine in Tinospora cordifolia and Tinospora sinensis. Indian J. Pharm. Sci. 70, 96–99. doi: 10.4103/0250-474X.40341
Srivastava, S. K., Rai, V., Srivastava, M., Rawat, A. K. S., and Mehrotra, S. (2006a). Estimation of heavy metals in different Berberis species and its market samples. Environ. Monit. Assess. 116, 315–320. doi: 10.1007/s10661-006-7395-x
Srivastava, S. K., Rawat, A. K. S., Manjoosha, S., and Mehrotra, S. (2006c). Pharmacognostic Evaluation of the Roots of Berberis chitria Lindl. Nat. Prod. Sci. 12, 19–23.
Srivastava, S. K., Rawat, A. K. S., and Srivastava, M. (2006b). Pharmacognostic evaluation of the roots of Berberis chitria. Nat. Prod. Sci. 12, 19–23.
Srivastava, S. K., Sayyada, K., Singh Rawat, A. K., and Mehrotra, S. (2001). Pharmacognostic evaluation of the root of Berberis aristata DC. Nat. Prod. Sci. 7, 102–106.
Srivastava, S. K., Singh Rawat, A. K., and Mehrotra, S. (2004). Pharmacognostic evaluation of the root of Berberis asiatica. Pharm. Biol. 42, 467–473. doi: 10.1080/13880200490886256
Srivastava, S. K., and Rawat, A. K. S. (2007). Pharmacognostic evaluation of the roots of Berberis tinctoria Lesch. Nat. Prod. Sci. 13, 27–32.
Steffens, P., Nagakura, N., and Zenk, M. H. (1985). Purification and characterization of the berberine bridge enzyme from Berberis beaniana cell cultures. Phytochemistry 24, 2577–2583. doi: 10.1016/S0031-9422(00)80672-X
Stermitz, F. (1967). Alkaloids of the Papaveraceae. V. Muramine and berberine from Argemone squarrosa. J. Pharm. Sci. 55, 760–762. doi: 10.1002/jps.2600560624
Stermitz, F. R., Lorenz, P., Tawara, J. N., Zenewicz, L. A., and Lewis, K. (2000). Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin, a multidrug pump inhibitor. Proc. Natl. Acad. Sci. U.S.A. 97, 1433–1437. doi: 10.1073/pnas.030540597
Stermitz, F. R., and Sharifi, I. A. (1977). Alkaloids of Zanthoxylum monophyllum and Z. punctatum. Phytochemistry 16, 2003–2006. doi: 10.1016/0031-9422(77)80113-1
Stermitz, F. R., Stermitz, J. R., Zanoni, T. A., and Gillespie, J. (1974). Alkaloids of Argemone subintegrifolia and A. munita. Phytochemistry 13, 1151–1153. doi: 10.1016/0031-9422(74)80089-0
Stuart, G. A., and Smith, F. P. (1977). Chinese Materia Medica: Vegetable Kingdom. Shanghai: Gordon Press Publishers.
Taborska, E., Frantisek, V., and Slavik, J. (1980). Alkaloids of the Papaveraceae. LXXI. Alkaloids from Bocconia frutescens L. Collect. Czechoslov. Chem. Commun. 45, 1301–1304. doi: 10.1135/cccc19801301
Tadzhibaev, M. M., Zatorskaya, I. N., Lutfullin, K. L., and Shakirov, T. T. (1974). Isolation of berberine. Khimiya Prir. Soedin. 10, 48–50. doi: 10.1007/BF00568218
Tan, E., Luo, S., Lin, S., Tan, R., Yu, W., Yi, Z., et al. (2013). Determination of five active ingredient in Phellodendron chinensis var. glabiusculum and P. chinense by HPLC. Zhongguo Shiyan Fangjixue Zazhi 19, 135–139.
Tang, J., Feng, Y., Tsao, S., Wang, N., Curtain, R., and Wang, Y. (2009). Berberine and Coptidis Rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations. J. Ethnopharmacol. 126, 5–17. doi: 10.1016/j.jep.2009.08.009
Tang, W., and Eisenbrand, G. (1992). “Corydalis turtschaninovii Bess. f. yanhusuo YH Chou et CC Hsü,” in Chinese Drugs of Plant Origin (Berlin; Heidelberg: Springer), 377–393.
Tantaquidgeon, G. (1928). Mohegan medicinal practices, weather-lore and superstitions. SI-BAE Annu. Rep. 43, 264–270.
Teng, H., and Choi, O. (2013). Optimum extraction of bioactive alkaloid compounds from Rhizome coptidis (Coptis chinensis Franch.) using response surface methodology. Solvent Extr. Res. Dev. 20, 91–104. doi: 10.15261/serdj.20.91
Thirupurasundari, C. J., Padmini, R., and Devaraj, S. N. (2009). Effect of berberine on the antioxidant status, ultrastructural modifications and protein bound carbohydrates in azoxymethane-induced colon cancer in rats. Chem. Biol. Interact. 177, 190–195. doi: 10.1016/j.cbi.2008.09.027
Tiwari, K. P., and Masood, M. (1979). Chemical constituents of Berberis coriaria Royle. J. Indian Chem. Soc. 56, 310–311.
Tiwary, J. K., Ballabha, R., and Tiwari, P. (2010). Ethnopaediatrics in Garhwal Himalaya. Uttarakhand, India (Psychomedicine Medice). NY Sci. J. 3, 123–126.
Tomè, F., and Colombo, M. L. (1995). Distribution of alkaloids in Chelidonium majus and factors affecting their accumulation. Phytochemistry 40, 37–39. doi: 10.1016/0031-9422(95)00055-C
Tomita, M., and Kugo, T. (1956). Alkaloids of Berberidaceous plants - XIX: Alkaloids of B. tschonoskyana I. Isolation of bases. Yakugak Zasshi 79, 317–321. doi: 10.1248/yakushi1947.79.3_317
Torres, R., Villarroel, L., Urzua, A., and Fajardo, V. (1992). Constituents of Berberis congestiflora and Berberis horrida. Fitoterapia 63:376.
Tsabang, N., Fokou, P. V. T., Tchokouaha, L. R. Y., Noguem, B., Bakarnga-Via, I., Nguepi, M. S. D., et al. (2012). Ethnopharmacological survey of Annonaceae medicinal plants used to treat malaria in four areas of Cameroon. J. Ethnopharmacol. 139, 171–180. doi: 10.1016/j.jep.2011.10.035
Uchiyama, T., Kamikawa, H., and Ogita, Z. (1989). Anti-ulcer effect of extract from Phellodendri cortex. Yakugaku zasshi J. Pharm. Soc. Japan 109, 672–676. doi: 10.1248/yakushi1947.109.9_672
Uniyal, S. K., Singh, K. N., Jamwal, P., and Lal, B. (2006). Traditional use of medicinal plants among the tribal communities of Chhota Bhangal, Western Himalaya. J. Ethnobiol. Ethnomed. 2:14. doi: 10.1186/1746-4269-2-14
Uprety, Y., Asselin, H., Boon, E. K., Yadav, S., and Shrestha, K. K. (2010). Indigenous use and bio-efficacy of medicinal plants in the Rasuwa District, Central Nepal. J. Ethnobiol. Ethnomed. 6:3. doi: 10.1186/1746-4269-6-3
Urzúa, A., Torres, R., Villarroel, L., and Fajardo, V. (1984). Secondary metabolites of Berberis darwinii. Rev. Latinoam. Quim. 15, 27–29.
Vennerstrom, J. L., and Klayman, D. L. (1988). Protoberberine alkaloids as antimalarials. J. Med. Chem. 31, 1084–1087. doi: 10.1021/jm00401a006
Vennerstrom, J. L., Lovelace, J. K., Waits, V. B., Hanson, W. L., and Klayman, D. L. (1990). Berberine derivatives as antileishmanial drugs. Antimicrob. Agents Chemother. 34, 918–921. doi: 10.1128/AAC.34.5.918
Versteegh, C. P. C., and Sosef, M. S. M. (2007). Revision of the African genus Annickia (Annonaceae). Syst. Geogr. Plants 77, 91–118.
Vuddanda, P. R., Chakraborty, S., and Singh, S. (2010). Berberine: a potential phytochemical with multispectrum therapeutic activities. Expert Opin. Investig. Drugs 19, 1297–1307. doi: 10.1517/13543784.2010.517745
Wang, C., Li, J., Lv, X., Zhang, M., Song, Y., Chen, L., et al. (2009). Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin. Eur. J. Pharmacol. 620, 131–137. doi: 10.1016/j.ejphar.2009.07.027
Wang, W., Shen, Q., Liang, H., Hua, C., Liu, Y., Li, F., et al. (2016). Pharmacokinetic studies of novel berberine derivatives with ultra-performance liquid chromatography–tandem mass spectrometry. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 1031, 172–180. doi: 10.1016/j.jchromb.2016.07.038
Wang, Y., Yi, X., Ghanam, K., Zhang, S., Zhao, T., and Zhu, X. (2014). Berberine decreases cholesterol levels in rats through multiple mechanisms, including inhibition of cholesterol absorption. Metabolism 63, 1167–1177. doi: 10.1016/j.metabol.2014.05.013
Watt, G. (1883). Economic Products of India, Calcutta International Exhibition. Calcuta: Medicinal Products, Superintendent of Government Print.
Weiner, M. A. (1980). Earth Medicine-Earth Food: Plant Remedies, Drugs, and Natural Foods of the North American Indians. New York, NY: Macmillan.
Willaman, J. J., and Schubert, B. G. (1961). Alkaloid-Bearing Plants and Their Contained Alkaloids (No. 1234). Agricultural Research Service, US Department of Agriculture.
Wu, X., Li, Y., Wang, Q., Li, W., and Feng, Y. (2015). Effects of berberine and pomegranate seed oil on plasma phospholipid metabolites associated with risks of type 2 diabetes mellitus by U-HPLC/Q-TOF-MS. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 1007, 110–120. doi: 10.1016/j.jchromb.2015.11.008
Xi, J. (2015). Ultrahigh pressure extraction of bioactive compounds from plants-a review. Crit. Rev. Food Sci. Nutr. 57, 1097–1106. doi: 10.1080/10408398.2013.874327
Xia, X., Yan, J., Shen, Y., Tang, K., Yin, J., Zhang, Y., et al. (2011). Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS ONE 6:e16556. doi: 10.1371/journal.pone.0016556
Xiao, H. B., Sun, Z. L., Zhang, H. B., and Zhang, D. S. (2012). Berberine inhibits dyslipidemia in C57BL/6 mice with lipopolysaccharide induced inflammation. Pharmacol. Rep. 64, 889–895. doi: 10.1016/S1734-1140(12)70883-6
Xiao, L., Xu, N., Guo, M., Guo, M., Lv, B, Tao, H., et al. (2014). Berberine protects endothelial progenitor cell from damage of TNF-alpha via the PI3K/AKT/eNOS signaling pathway. Eur. J. Pharmacol. 743, 11–16. doi: 10.1016/j.ejphar.2014.09.024
Xu, B., Li, P., and Zhang, G. (2015). Comparative pharmacokinetics of puerarin, daidzin, baicalin, glycyrrhizic acid, liquiritin, berberine, palmatine and jateorhizine by liquid chromatography-mass spectrometry after oral administration of Gegenqinlian decoction and active components alignmen. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 988, 33–44. doi: 10.1016/j.jchromb.2015.01.039
Xu, K., He, G., Qin, J., Cheng, X., He, H., Zhang, D., et al. (2017). High-efficient extraction of principal medicinal components from fresh Phellodendron bark (Cortex phellodendri). Saudi J. Biol. Sci. 25, 811–815. doi: 10.1016/j.sjbs.2017.10.008
Yang, L., Meng, X., Yu, X., and Kuang, H. (2017). Simultaneous determination of anemoside B4, phellodendrine, berberine, palmatine, obakunone, esculin, esculetin in rat plasma by UPLC-ESI-MS/MS and its application to a comparative pharmacokinetic study in normal and ulcerative colitis rats. J. Pharm. Biomed. Anal. 134, 43–52. doi: 10.1016/j.jpba.2016.11.021
Yang, T.-H. (1960a). Alkaloids of Berberidaceae. XXIX. Alkaloids of Mahonia lomariifolia and M. morrisonensis. Yakugaku Zasshi 80, 1304–1307. doi: 10.1248/yakushi1947.80.9_1304
Yang, T.-H. (1960b). Alkaloids of Berberidaceae. XXVIII. Alkaloids of Berberis morrisonensis. Yakugaku Zasshi 80, 1302–1304. doi: 10.1248/yakushi1947.80.9_1302
Yang, T.-H., and Lu, S.-T. (1960a). Alkaloids of berberidaceous plants. XXV. Alkaloids of Berberis kawakamii. 1. Yakugaku Zasshi 80, 847–849. doi: 10.1248/yakushi1947.80.6_847
Yang, T.-H., and Lu, S.-T. (1960b). Alkaloids of berberidaceous plants. XXVI. Alkaloids of Berberis mingetsensis. 1. Yakugaku Zasshi 80, 849–851. doi: 10.1248/yakushi1947.80.6_849
Yavich, P. A., Kakhtelidze, M. B., and Sarabunovich, A. G. (1993). Quantitative determination of berberine in Phellodendron lavallei bark. Farmatsiya 42, 49–50.
Yeung, H. (1985). Handbook of Chinese Herbs and Formulas, Vol. 1. Los Angeles, CA: Institute of Chinese Medicine.
Yin, J., Gao, Z., Liu, D., Liu, Z., and Ye, J. (2008a). Berberine improves glucose metabolism through induction of glycolysis. Am. J. Physiol. Endocrinol. Metab. 294, E148–E156. doi: 10.1152/ajpendo.00211.2007
Yin, J., Xing, H., and Ye, J. (2008b). Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 57, 712–717. doi: 10.1016/j.metabol.2008.01.013
Yogesh, H. S., Chandrashekhar, V. M., Katti, H. R., Ganapaty, S., Raghavendra, H. L., Gowda, G. K., et al. (2011). Anti-osteoporotic activity of aqueous-methanol extract of Berberis aristata in ovariectomized rats. J. Ethnopharmacol. 134, 334–338. doi: 10.1016/j.jep.2010.12.013
Yoo, S. J., Lee, K. B., and Kwak, J. H. (1986). Studies on the seasonal variation of berberine contents in Berberis koreana. Saengyak Hakhoechi 17, 123–128.
Yu, C., Tan, S., Zhou, C., Zhu, C., Kang, X., Liu, S., et al. (2016). Berberine reduces uremia-associated intestinal mucosal barrier damage. Biol. Pharm. Bull. 39, 1787–1792. doi: 10.1248/bpb.b16-00280
Zabihullah, Q., Rashid, A., and Akhtar, N. (2006). Ethnobotanical survey in kot Manzaray Baba valley Malakand agency, Pakistan. Pak. J. Plant Sci. 12, 115–121.
Zaha, V. G., Qi, D., Su, K. N., Palmeri, M., Lee, H. Y., Hu, X., et al. (2016). AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia. J. Mol. Cell. Cardiol. 91, 104–113. doi: 10.1016/j.yjmcc.2015.12.032
Zaman, M. B., and Khan, M. S. (1970). Hundred drug plants of West Pakistan. Medicinal Plant Branch of Pakistan Forest Institute.
Zeng, X. (1999). Relationship between the clinical effects of berberine on severe congestive heart failure and its concentration in plasma studied by HPLC. Biomed. Chromatogr. 13, 442–444. doi: 10.1002/(SICI)1099-0801(199911)13:7<442::AID-BMC908>3.0.CO;2-A
Zhang, J., Cai, C. T., Cai, Z. Q., Liu, G. Z., Luo, Y., and Yang, Z. X. (2008). Variation patterns of Coptis teeta biomass and its major active compounds along an altitude gradient. J. Appl. Ecol. 19, 1455–1461.
Zhao, X., Zhang, J., Tong, N., Chen, Y., and Luo, Y. (2012). Protective effects of berberine on Doxorubicin-induced hepatotoxicity in mice. Biol. Pharm. Bull. 35, 796–800. doi: 10.1248/bpb.35.796
Keywords: berberine, botanical occurrence, traditional uses, extraction methods, biological activities
Citation: Neag MA, Mocan A, Echeverría J, Pop RM, Bocsan CI, Crişan G and Buzoianu AD (2018) Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front. Pharmacol. 9:557. doi: 10.3389/fphar.2018.00557
Received: 21 December 2017; Accepted: 09 May 2018;
Published: 21 August 2018.
Edited by:
Anna Karolina Kiss, Medical University of Warsaw, PolandReviewed by:
Pinarosa Avato, Università degli Studi di Bari Aldo Moro, ItalySylwia Zielinska, Wroclaw Medical University, Poland
Copyright © 2018 Neag, Mocan, Echeverría, Pop, Bocsan, Crişan and Buzoianu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Andrei Mocan, mocan.andrei@umfcluj.ro