Ram Bharti1,2
Neeraj Khatri- 1IMTECH Centre for Animal Resources & Experimentation (iCARE), Council of Scientific and Industrial Research-Institute of Microbial Technology (CSIR-IMTECH), Chandigarh, India
- 2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
Puerariatuberosa (Roxb. ex Willd.) DC. (Fabaceae), also known as Indian Kudzu (vidari kand), is a perennial herb distributed throughout India and other Asian countries. Traditionally, tuber and leaves of this plant have extensively been reported for nutritional and medicinal properties in Ayurveda as well as in Chinese traditional practices. The objective of the present review is to compile and update the published data on traditional uses, pharmacological potential, and phytochemistry of compounds isolated from the plant Pueraria tuberosa. P. tuberosa extracts and its purified compounds possess multiple activities such as anticancer, anticonvulsant, antidiabetic, antifertility, anti-inflammatory, antioxidant, anti-stress, antiulcerogenic, cardioprotective, hypolipidemic, hepatoprotective, immunomodulatory, nephroprotective, nootropic, neuroprotective, and wound healing. Tuber and leaf extracts of P. tuberosa contain several bioactive constituents such as puerarin, daidzein, genistein, quercetin, irisolidone, biochanin A, biochanin B, isoorientin, and mangiferin, which possess an extensive range of pharmacological activities. The extensive range of pharmacological properties of P. tuberosa provides opportunities for further investigation and presents a new approach for the treatment of ailments. Many phytochemicals have been identified and characterized from P. tuberosa; however, some of them are still unexplored, and there is no supporting data for their activities and exact mechanisms of action. Therefore, further investigations are warranted to unravel the mechanisms of action of individual constituents of this plant.
Introduction
As per the World Health Organization (WHO) estimation, about 65–80% of people all over the world seek herbal therapies to cure primary health conditions (Robinson and Zhang, 2011). Surprisingly, only 15% of the global flora has been assessed for pharmacological potential (De Luca et al., 2012). WHO has published four volumes of the monographs on selected medicinal plants to support the research in the field of herbal medicine (WHO, 2009). In India, Ayurveda, Unani, Siddha, Homeopathy, and Folk medicine are commonly used as traditional alternative medicine practices for treating different ailments. Among the modern civilizations, India has long been known for its rich treasure of medicinal plants, and about more than 7,000 plant remedies have been categorized and documented by the AYUSH system of medicine (National Medicinal Plants Board, Government of India, 2020). One of the medicinally important plants discussed in this review is Pueraria tuberosa (Roxb. ex Willd.) DC. (Fabaceae), also known as Indian Kudzu (vidari kand). It is a rapidly growing large perennial climber with big tuberous roots (Figures 1–4) (Indian Medicinal Plant Database) and is distributed throughout India, Pakistan, and Nepal (Keung, 2002). Lianas of P. tuberosa has also been found to grow at 4,000 feet in the Himalayan mountain series (Pueraria tuberosa—Vikaspedia, 2020). In Ayurveda, it is known as vidari (vidari kand). The tuber of this plant is sweet (Ayurvedic pharmacopoeia of India, 2001) and is widely used in the treatment of fever, menorrhagia, skin diseases, wounds, bronchial asthma, and jaundice. Apart from the traditional uses of this plant as mentioned in ancient literature like Sushruta Samhita (Sanskrit: सुश्रुत संहिता), several studies have been reported on different pharmacological activities of P. tuberosa extracts and its purified compounds, viz., anticancer (Adedapo et al., 2017), anticonvulsant (Basavaraj et al., 2011), antidiabetic (Oza and Kulkarni, 2018a), antifertility (Gupta et al., 2005), anti-inflammatory (Tripathi et al., 2013), antioxidant (Shukla et al., 2018a), anti-stress (Verma et al., 2012), antiulcerogenic (Gindi et al., 2010), cardioprotective (Patel et al., 2018), hypolipidemic (Tanwar et al., 2008), hepatoprotective (Xia et al., 2013), immunomodulatory (Patel et al., 2016), nephroprotective (Shukla et al., 2018b), nootropic (Rao et al., 2008), neuroprotective (Xing et al., 2011), and wound healing activities (Kambhoja and Murthy, 2007). Previously, Maji et al. (2014) broadly highlighted the phytochemical and therapeutic potential of P. tuberosa in various pharmacological activities. However, the information about the doses of plant extracts used and the models implied for the studies (in vitro or in vivo) in different pharmacological activities was missing. In addition, chemical structures of only few phytoconstituents isolated from P. tuberosa have been given. Therefore, this review is aimed to provide an up-to-date summary of the literature on traditional uses, doses, and types of studies used to confirm pharmacological activities and phytochemical constituents isolated from P. tuberosa plant with their chemical structures and IUPAC names.
FIGURE 1. Pueraria tuberosa (Roxb. ex Willd.) DC. (Fabaceae): (1) Leaf. (2–4) Tuber.
FIGURE 2. Indian Medicinal Plant database.
FIGURE 3. Pankaj Oudhia/https://www.discoverlife.org.
FIGURE 4. “Pueraria tuberosa (Willd.) DC. Vidari Kand, Patal Kumrha”, by Ravi Upadhyay, https://indiabiodiversity.org/observation/show/269544, licensed under CC BY 3.0).
Methodology
Relevant literature for this review on P. tuberosa has been sourced from PubMed, ScienceDirect, Web of Science, PubChem, Google Scholar, SciFinder, and Scopus database. The articles published in English before September 2020 on traditional uses, pharmacology of extracts, and various phytoconstituents isolated from different parts of P. tuberosa were included in this review. The keywords used for retrieving relevant studies were Pueraria tuberosa plant, Indian Kudzu, vidari kand, tuber extract, traditional uses, phytochemical constituents, pharmacological activity, and in silico, in vitro, and in vivo studies.
Data inclusion criteria included (a) published/peer-reviewed scientific manuscripts; (b) ethnopharmacological studies; (c) tuber extracts with different solvents; (d) studies on the mechanism of actions of plant extracts and their phytoconstituents; (e) in silico, in vitro, and in vivo studies. Exclusion criteria included (a) repetitive studies and information not meeting the inclusion criteria; (b) studies performed with extracts of other Pueraria species; (c) opinion to the editors, case studies, abstracts of the conferences, any unpublished data, and reports.
Synonyms (Ayurvedic pharmacopoeia of India, 2001)
Assamese: Bhedeleton, Bhuikumra
Bengali: Bhuinkumra, Bhumikusmanda, Vidari
English: Indian kudzu
Gujrati: Bhoikolu, Bhonykoru, Eagio, Sakharvel, Vidarikanta,
Hindi: विदारीकंद (Vidarikanda), बनकुमड़ा (Bankumara)
Kannada: Gumadi belli, Gumadigida, Nelagumbala Gudde, Nelagumbala, Nelagumbula
Malayalam: Mudakku
Marathi: Bhuikohala, Ghodvel
Oriya: Bhuiankakharu
Punjabi: Siali, Surala
Sanskrit: भूमिकुष्माण्ड (Bhumikusmanda), गजवाजिप्रिया (Gajavajipriya), कन्दपलाश (Kandapalash), स्वादुकन्दा (Svadukanda), विदारी (Vidari), इक्षुगन्धा (Iksu-Gandha).
Tamil: Nilapoosani
Telugu: Darigummadi, Nelagummuda
Scientific Classification (Rawtal et al., 2019)
Kingdom: Plantae
Subkingdom: Trachebionta
Superdivision: Spermatophyta
Division: Magnoliophyta
Subclass: Rosidae
Order: Fabales
Family: Fabaceae
Genus: Pueraria DC.
Species: Pueraria tuberosa
Traditional Uses
In Ayurveda, vidari kand (Pueraria tuberosa) has been described as a plant having good nutritional value. Besides, the plant also possesses aphrodisiac, diuretic, galactagogue (Kirtikar and Basu, 1935), energizing (Maji et al., 2014), and spermatogenic (Chauhan et al., 2013) properties. It has been prescribed for treatment for all three doshas (i.e., for the complications of three different energies, viz., Vata, Kapha, and Pitta) of human body (Ayurvedic pharmacopoeia of India, 1999; Dalal et al., 2013). The powdered form of tuber is primarily used in combination with cow’s milk as a galactagogue agent to abrogate lack of milk production after childbirth and also as an anabolic agent along with Piper longum L. (Piperaceae) powder to cure malnutrition in children. For relieving excessive menstruation, the powder is used with honey. A mixture of powdered P. tuberosa and wheat or barley fried in ghee (clarified butter) with milk has been advised for sexual enervation and strength. For spermatorrhoea, fresh tuber juice of this plant with cumin seeds and sugar has been used therapeutically (Puri, 2003).
Traditionally, P. tuberosa has been used along with other medicinal plants in different combinations to prepare therapeutic Ayurvedic formulation. Some of the important Ayurvedic formulations utilizing P. tuberosa are “Ashwagandharishta”, a traditional remedy for epilepsy (Tanna et al., 2012), “Maha visagarbha taila”, a traditional remedy for sciatica and joint disorders (Kumawat et al., 2017), and “Nityananda rasa”, “Sarasvatarista”, “Satavaryadi ghrta” (Ayurvedic pharmacopoeia of India, 2001), “Marma gutika” (Kumar, 2016), and “Vidaryadi ghrita” (Sharma et al., 2018).
Traditional uses of Pueraria species, namely, Pueraria montana var. thomsonii (Benth.) (Fabaceae) and Pueraria montana var. lobata (Willd.) (Fabaceae), have been reported for their medicinal properties such as antiemetic, antitoxic, cold, countering the effect of alcohol abuse, anti-stress agent, neck stiffness, hypohidrosis, migraines, hypoglycemia, and certain cardiovascular diseases in the Chinese Medicinal Herbs, a book written by Li Shih Chen (Li, 2003; Croom, 2004).
Pharmacology
In phytopharmacological/ethnopharmacological research, scientific community should follow best practices in designing and conducting studies and reporting the results of analyzing pharmacological properties of the plant extracts and compounds of natural origin (Heinrich et al., 2020). Therefore, while reporting biological activities of any plant/herbal product, detailed information about the characterization of the plant extracts, their phytoconstituents, doses, duration of treatment, type of models used in the studies, toxicological data, and so forth should be clearly presented for the benefit of research community (Heinrich et al., 2020). Various pharmacological activities of the tuber extracts of P. tuberosa have been explored, and a graphical summary of these activities is shown in Figure 5 and Table 1.
FIGURE 5. Pharmacological activities of Pueraria tuberosa.
TABLE 1. Pharmacological activities of tuber extract of Pueraria tuberosa.
Nephroprotective Activity
Several studies have shown that P. tuberosa plant possesses nephroprotective activities. Oral administration of methanolic tuber extract to cisplatin- (8 mg/kg body weight) induced kidney damaged rats showed a dose-dependent protective effect (Nagwani and Tripathi, 2010). Tuber extract significantly reduced blood urea nitrogen, serum creatinine, glutathione, and superoxide dismutase (SOD) levels. The extract could control deoxyribonucleic acid (DNA) damage and catalase activities, cellular necrosis, and tubular swelling and prevent coagulation of proteins, in contrast to the control group. The nephroprotection of tuber extract of the plant has been attributed to its free radical scavenging activity (Nagwani and Tripathi, 2010). Feeding of biscuits made up of powder of P. tuberosa tuber for 10 days showed significant recovery in cisplatin-induced nephrotoxicity in Swiss mice. However, at higher dose, aspartate aminotransferase and alanine aminotransferase levels were temporarily elevated, so monitoring of liver functions, periodically, is imperative when continuing this regimen for longer periods such as a food supplement for cancer patients undertaking cisplatin chemotherapy (Tripathi et al., 2012). The methanolic extract of P. tuberosa ameliorated glycerol-induced acute kidney injury in rats by affecting the lipid peroxidation, SOD, and catalase activity with a lesser accumulation of hyaline casts and a lesser degree of tubular necrosis on histology of the kidney (Yadav et al., 2016a). Water decoction of P. tuberosa has also been reported to significantly reverse cisplatin-induced nephrotoxicity in rats (Yadav et al., 2016b). Hydroalcoholic tuber extracts of P. tuberosa showed nephroprotective activity in sodium arsenate- (1 mg/kg body weight) induced oxidative kidney tissue damage in rats (Rani et al., 2017). The nephroprotective effect through free radical scavenging activity was supported in a study, where streptozotocin- (STZ-) induced diabetic nephropathic rats, treated with aqueous tuber extract of P. tuberosa, exhibited an upsurge in activity of antioxidant enzymes, lowered oxidative stress, apoptosis, and urinary albumin excretion in a concentration-dependent manner (Shukla et al., 2018a). Methanolic tuber extract of the plant showed substantial protection in diabetic nephropathy induced by the administration of alloxan in rats (120 mg/kg body weight) by decreasing urea and creatinine and improving physiology of the kidney (Yadav et al., 2019). The supplementation of tuber extract of the P. tuberosa showed protection of kidney from oxidative stress and cellular injury. It also improved kidney physiology and parameters of kidney function test by reducing cellular apoptosis. These studies indicate that P. tuberosa extracts have nephron-protective potential and might lead to promising therapeutic agents for treating kidney diseases.
Antioxidant Activity
Methanolic and hexane tuber extract of P. tuberosa exhibited a strong free radical scavenging activity in a concentration-dependent fashion. These results showed that the methanolic extract of this plant exhibited better activity than the hexane extract in trapping hydroxyl radicals and inhibited lipid peroxidation, which indicated potent antioxidant property (Pandey et al., 2007). Hot water tuber extract of the plant P. tuberosa, supplemented with milk in Swiss mice, showed potent antioxidant activities in liver and red blood cells. Besides, a remarkable difference in glutathione levels was also observed in the control (172 μg/ml) and supplemented groups (P. tuberosa: 1,212 μg/ml and P. tuberosa + milk: 1,308.2 μg/ml). P. tuberosa along with milk has antioxidant property as evidenced by higher phagocytic activity, increased immunoglobulin levels, and reduced glutathione and lipid peroxidation (Sawale et al., 2013). P. tuberosa extracted with chloroform, acetone, methanol, and hot water was used to determine its antioxidant potential by using ferric reducing antioxidant power (FRAP) assay, metal chelating, phosphomolybdenum, and free radical scavenging using DPPH (2,2′-diphenyl-1-picrylhydrazyl radical) and ABTS (3-ethylbenzothiazoline-6-sulfonic acid) assay. The results showed that acetone extract of P. tuberosa has potent antioxidant activity (Viji and Paulsamy, 2015).
Antidiabetic Activity
Oral gavage of ethyl acetate tuber extract of P. tuberosa (250 mg/kg body weight) to alloxan-induced diabetic rats for seven days showed a pronounced decrease in blood glucose levels (Raghuwanshi and Jain, 2011). Studies suggested that chloroform, petroleum ether, ethanol, and aqueous tuber extracts of P. tuberosa confer significant antidiabetic activity in STZ- (50 mg/kg body weight) induced diabetic rats by a single intraperitoneal injection (Tripathi and Kohli, 2013). Water extract of root of P. tuberosa showed significant inhibition of dipeptidyl peptidase-4 (DPP-IV) that causes an enhanced half-life of active glucagon-like peptide-1 hormone. This hormone regulates glucose-dependent insulin release from β-cells of the pancreas in rats (Srivastava et al., 2015). In Srivastava et al.’s next study, they found that P. tuberosa water extract increased the glucose homeostatic potential through DPP-IV inhibitory pathway and the bioactive components robinin and puerarone, and this inhibitory activity was also confirmed by in silico molecular docking (Srivastava et al., 2017). Aqueous extract of tuber of P. tuberosa has further been reported to act as incretin receptor agonist and downregulated β-cells apoptosis and protected STZ-induced diabetes in rats (Srivastava et al., 2018). Aqueous tuber extract of the plant showed an elevated expression of nephrin and SOD and a declined expression of cysteinyl aspartate specific proteinase 3 (caspase-3), interleukin 6 (IL-6), nuclear factor kappa B (NF-κB), protein kinase C epsilon type (PKCε), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and hypoxia-inducible factor 1-alpha in STZ-induced diabetic rats (Srivastava et al., 2019). In another experiment, it has been shown that administration of P. tuberosa water extract in alloxan-induced rat diabetic model resulted in decrease in SGOT (serum glutamic oxaloacetic transaminase), SGPT (serum glutamic pyruvic transaminase), and alkaline phosphates level and improved deformed hepatocytes and significant decrease in blood glucose levels as well as apoptosis (Pandey et al., 2019). The tuber extract contains different bioactive compounds that may act as agonists on glucagon-like peptide-1 hormone released from intestine and can also protect β-cells of the pancreas. It also resulted in decreased expression of different inflammatory and apoptotic markers during hypoxic injury to β-cells as evidenced by decreased apoptosis of β-cells. The extract also inhibited DPP-IV enzyme as an incretins receptor agonist, and hence it is emanating from the above studies that P. tuberosa has antidiabetic potential.
Anti-Stress Activity
Adult male Wistar rats subjected to cold immobilization stress, pretreated with 70% hydroethanolic tuber extract of P. tuberosa (200 and 400 mg/kg body weight) for 5 days, showed significant protection from gastric mucosal damage, reduced corticosterone level in the blood, and no enlargement of spleen and adrenals as compared to Withania somnifera (L.) Dunal (Solanaceae) rhizome extract (100 mg/kg body weight). These studies established the anti-stress effect of P. tuberosa (Pramanik et al., 2011). In a human trial, hypertensive patients were divided into two groups: group 1 was given capsules with 0.75 g tuber powder, whereas group 2 was given placebo capsules with lactose powder administered for 12 weeks. Group 1, treated with 1.5 g (twice a day) tuber powder of P. tuberosa for 12 weeks, showed a gradual decrease in systolic, diastolic, and mean blood pressure as well as a tolerant decrease in fibrinogen and increased plasma fibrinolytic activity (Verma et al., 2012). In stress-mediated disorders, the hypothalamic-pituitary-adrenal (HPA) axis is dysregulated which changes the levels of corticosteroids in plasma and monoamine in the brain. The extract of this plant might act on mucosal layer of the gastrointestinal, cardiovascular, and nervous (HPA) system, suggestive of anti-stress activity by a reduction in stress hormones.
Antidiabetic Nephropathic Activity
STZ-induced diabetic rats with nephropathy were given tuber extract of P. tuberosa (30 mg/100 g, body weight) for 20 days and exhibited a significant reduced severity of diabetic nephropathy by enhanced expression and activity of MMP-9 and degrading the accumulation of extracellular matrix in kidney tissue (Tripathi et al., 2017). Levels of nephrin, a biomarker of early glomerular injury, in the kidney of diabetic nephropathic rats were restored after treatment with tuber extract of P. tuberosa (Shukla et al., 2017). The diabetic nephropathic inflammatory response is mediated by NF-κB and its activated phosphorylated derivative (pNF-κB). Improved levels of these transcription factors and inflammatory cytokines (IL-6 and TNF-α) in the kidney of STZ-induced (55 mg/kg body weight) diabetic nephropathic rats were observed, and treatment with extracts from the tuber of P. tuberosa significantly negated these changes in a dose-dependent manner (Shukla et al., 2018b). Amelioration of renal damage was evaluated by renal functional tests, histopathology, and oxidative stress in alloxan-induced diabetic nephropathy. P. tuberosa methanolic extract showed renal protection by decreasing urea and creatinine and improved kidney physiology and histopathology changes through antioxidant mechanisms (Yadav et al., 2019). These studies are indicative of nephro-protection offered by P. tuberosa in diabetic nephropathy; however, this protective effect needs to be further explored, including studies on the protection of renal and glomerular cells mediated by different signaling pathway in the antidiabetic nephropathy.
Anti-Inflammatory Activity
The ethyl acetate and methanolic tuber extracts of P. tuberosa showed considerable anti-inflammatory potential compared to the control and standard drugs, ibuprofen, and nitrofurazone ointment in the rat paw edema method (Kambhoja and Murthy, 2007). The methanolic tuber extract of the plant significantly prevented the carrageenan-induced inflammation by lowering the glutathione content, catalase, SOD activity, and enhancing lipid peroxidase and C-reactive proteins in rats in a sequential manner (Tripathi et al., 2013). Isoorientin, isolated from the tuber of P. tuberosa plant, showed significant anti-inflammatory activity in LPS-treated mouse macrophage (RAW 264.7) cell line. It was also effective against carrageenan-induced inflammation on paw edema and air pouch mouse models. These studies revealed the downregulation in the expression of proinflammatory genes such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and inactivation of NF-κB. Moreover, there was activation of antioxidant enzymes, catalase and glutathione-S-transferase (Anilkumar et al., 2017). The anti-inflammatory property of extracts of P. tuberosa in these studies appears to be mediated by lipid peroxidation, inactivation of the NF-κB pathway, and downregulation of proinflammatory cytokines.
Immunomodulatory Activity
Immunomodulatory activities of plant extract (0.4%) with milk as a carrier given to Swiss mice for 28 days were evaluated. The result showed a significantly higher phagocytic activity and immunoglobulin concentration, reduced glutathione content, and thiobarbituric acid reactive substances level compared to the control (Sawale et al., 2013). Reversed phase high-performance liquid chromatography (RP-HPLC) analysis of ethanolic tuber extract of the plant revealed that bioactive compounds involved in the immunomodulatory activities are genistein (1.37%), daidzein (1.70%), and puerarin (8.31%). Oral administration of these extracts builds up innate and humoral immune responses against sheep red blood cells challenged rats (Maji et al., 2014). The immunomodulatory activity of petroleum ether extract of P. tuberosa was evaluated by carbon clearance assay (Granulopectic index). The extract and Withania somnifera (L.) Dunal (Solanaceae) at 250 mg/kg body weight (Medicinal Plant Names Services, e) exhibited enhanced phagocytic activity of peritoneal macrophages to clear the carbon particles (Shilpashree et al., 2015). The ethanolic extract of tuber increased the phagocytic activity of macrophages in the mice model. The extract also inhibited both the cell mediated and humoral immunity, which supports its potent immunomodulatory activity (Patel et al., 2016).
Anticancer Activity
There is no significant toxicity of mangiferin isolated from tuber of P. tuberosa on normal cell lines (mouse fibroblast NIH-3T3, RAW 264.7, HEK293, and mouse lymphocytes) in cell viability assay in vitro; however, it is cytotoxic to various cancer cell lines like K562, MCF7, HEPG2, Jurkat cells, and A549 (Bulugonda et al., 2017). Furthermore, the anticancer and apoptotic potential of the hydroalcoholic tuber extract of P. tuberosa was investigated by cell viability assay. The extract showed a 50% inhibition of cell viability against human colon carcinoma (HT-29) cells at a concentration of 63.91 µg/ml. Cells also exhibited DNA fragmentation that is the hallmark of apoptosis, apoptotic cell death, and increased expression of certain proapoptotic genes (Aruna et al., 2018). The silver nanoparticles biosynthesized with aqueous extract of the P. tuberosa showed in vitro anticancer potential on different cancer cell lines (breast MCF-7 and MDA-MB-231; ovarian SKOV-3; brain U-87 cancer). However, the mechanism behind this activity needs exploration for therapeutic use (Satpathy et al., 2018). Antioxidant-enriched fraction also exhibited in vitro cytotoxicity in the breast (MCF-7 and MDA-MB-231) and ovarian (SKOV-3) cancer cells (Satpathy et al., 2020).
Other Pharmacological Properties
P. tuberosa has been attributed as one of the most sought plants that proved to be effective against multiple diseases and ailments. Alcoholic and aqueous extracts of P. tuberosa tuber were studied for nootropic effect in mice and rat models of amnesia induced by scopolamine and diazepam. The inflexion ratio observed was considerably high and comparable with piracetam, the standard drug in an elevated plus-maze experiment. Flavonoids present in the P. tuberosa tuber extracts have been reported for nootropic effect by interacting with cholinergic, adrenergic, serotonergic, and GABAnergic system (Rao et al., 2008). The neuroprotective properties of this plant were also studied in chronic foot-shock stressed rat model showing unpredictable and inescapable nature of physiological malfunctions, increase in anxiety level, decrease in male sexual indices, and behavioral changes. All these symptoms were abolished by this plant’s tuber extract (Pramanik et al., 2010). Neurotoxicity induced by sodium arsenate was ameliorated by hydroalcoholic extract which strengthens its memory and restores muscle strength and locomotor activity. Biochemical and histopathological changes are suggestive of the protective property of the extract in maintaining normal functional status of the brain in arsenate neurotoxicity (Umarani et al., 2016).
Alcoholic tuber extract of P. tuberosa was studied for anticonvulsant activity in pentalene tetrazole, strychnine, and maximal electroshock-induced convulsions in animals. Different doses of the extract (50, 100, and 200 mg/kg body weight) were compared with the standard drug, diazepam (5 mg/kg body weight). The medium and high doses exhibited potent anticonvulsant activity as compared to the control group (Basavaraj et al., 2011). The ethanolic and methanolic extract of leaf, stem, and tuber of P. tuberosa showed a wide range of antimicrobial activity against bacteria, Escherichia coli, Bacillus cereus, Salmonella paratyphi, and Staphylococcus aureus, as well as fungus, Candida albicans, Aspergillus fumigates, and Alternaria solani, on agar diffusion assay (Sadguna et al., 2015). The tuber extracts of P. tuberosa with different solvents exhibited a wide range of antimicrobial activity on selected bacterial and fungal pathogens (Aruna et al., 2016). The chloroform and water extracts of tuber of P. tuberosa showed significant antibacterial activity against Klebsiella pneumoniae and Staphylococcus aureus and methanolic extract on Staphylococcus aureus and Streptococcus agalactiae (Pandya et al., 2019). The metabolites in P. tuberosa extracts may be behind the mechanism involved in the antimicrobial action, which may interact with the microbial cell membrane resulting in microbial cell death. The antiulcerogenic activity of aqueous leaf extract of P. tuberosa on cold restraint stress, pyloric ligation, and ethanol-induced gastric ulcer rat models was observed. There was significant inhibition in gastric lesions by 76.6% in cold restraint stress, 80.1% in pyloric ligation, and 70.6% in ethanol-induced rat models (Gindi et al., 2010).
In metabolic disorders also, P. tuberosa extracts exhibited a hypolipidemic effect. Oral administration of butanol tuber extract of P. tuberosa at a dose of 150 mg/kg body weight showed a pronounced protective effect against CCl4-induced hepatotoxicity in adult male rats (Shukla et al., 1996). Rats maintained on high cholesterol diet upon the treatment demonstrated a substantial reduction in serum cholesterol, triglycerides (TG), low-density lipoproteins (LDL), and very-low-density lipoproteins (VLDL) levels (Tanwar et al., 2008). These results were corroborated in another study where nonalcoholic fatty liver disease (NAFLD), induced in rats by feeding a high fat diet, was treated with water extract of this plant. Antioxidant activity with reduced lipid peroxidation and enhanced activities of SOD and catalase enzymes were observed. A similar finding was observed by Tripathi et al. in the NAFLD rats model which also showed a reduction in serum TG and cholesterol values (Tripathi and Aditi, 2020). The ethanolic extract of P. tuberosa showed a dose-dependent immunosuppressant activity as evident by a decrease in antibody titer and also a reduction in hematological parameters in the drug-induced myelosuppression model (Babu et al., 2016). Crude powder (3 g daily) of P. tuberosa tuber was given to a human patient with ischemic heart disease for twelve months. The case study demonstrated an overall significant cardioprotective effect; resting mean blood pressure was reduced from 96.66 to 90.00 mm Hg without affecting the resting heart rate, and the heart rate at peak exercise was also reduced, indicating better exercise tolerance (Verma et al., 2009).
P. tuberosa root extract, given to male Wistar rats (100 mg/rat per day) for 60 days, affected the fertility of rats as shown by a reduction in weight of testes, epididymis, prostate, and the seminal vesicle. Studies also showed a considerable decrease in the quantity of mature Leydig cells, cauda epididymis, and sperm motility (Gupta et al., 2005). The antioxidant-enriched fraction from the tuber extract of P. tuberosa against menopausal osteoporosis in ovariectomy-induced osteoporosis in rats was studied and found that it improved biochemical parameters, controlled the increased body weight, and decreased uterus weight following ovariectomy as well as restoration of typical bone structure and trabecular width of the femur (Satpathy et al., 2020). Incision and excision wounds were treated with methanolic and ethyl acetate tuber extract of P. tuberosa. The extracts showed potent wound healing property in comparison to the control and the group of rats treated with standard drugs, ibuprofen, and nitrofurazone ointment (Kambhoja and Murthy, 2007).
Phytochemistry
The crude tuber extracts of P. tuberosa are known to contain alkaloids, anthracene, anthocyanidins, anthraquinone, glycosides, carbohydrates, catecholic compounds, coumarins, flavonoids, glycosides, hexose sugars, saponins, steroids, terpenoids, and volatile oils (Ratnam and Venkata Raju, 2009; Rawtal et al., 2019). Therefore, many studies have been undertaken to individually analyze and characterize the activities of different phytoconstituents of the plant. Vaishnav et al. could grow a callus culture of P. tuberosa and identified four isoflavanoids, viz., puerarin [1], daidzein [2], genistin [3], and genistein [4] (Vaishnav et al., 2006; Satpathy et al., 2017). Lupinoside PA4 [5] was isolated from methanolic extract of P. tuberosa using HPLC, and its structure was determined by 1D, 2D NMR, and Q-TOF-MS (Dey et al., 2007). Pandey and Tripathi extracted tuberosin [6], 3-O-methylanhydrotuberosin [7], and puerarostan [8] from ethanolic tuber extract; the same was confirmed by UV, IR, and NMR spectral data (Pandey and Tripathi, 2010). β-Sitosterol [9] was quantified in the methanolic root extract of P. tuberosa by high-performance thin layer chromatography (HPTLC) method (Mhaske et al., 2009). Liquid chromatography–mass spectrometry (LC–MS) analysis of ethanolic extract was found to contain puerarin, daidzein, biochanin A [10], and biochanin B [11] (formononetin) (Chauhan et al., 2013). Daidzin [12], irisolidone [13], 4-methoxypuerarin [14], puerarone [15], quercetin [16], and tectoridin [17] are the flavonoid compounds and p-coumaric acid [18], which have been reported to be isolated from tuber of P. tuberosa (Maji et al., 2014) and aqueous tuber decoction shown to contain daidzein, genistin, hydroxytubersone [19], puerarin, puetuberosanol [20], robinin [21], tuberosin, and tuberostan [22] (Shukla et al., 2017). Mass spectrometry and 2D-NMR techniques were used to isolate isoorientin [23] and mangiferin [24] from methanolic extract from P. tuberosa (Sumalatha et al., 2015). Phytochemical analysis of P. tuberosa extract using HPTLC revealed the presence of carbohydrates, proteins, alkaloids, flavonoids, saponins, phenols, and tannins (Viji and Paulsamy, 2018). Satpathy et al. showed the presence of 23 bioactive molecules including stigmasterol [25], β-sitosterol, and stigmasta-3,5-dien-7-one by gas chromatography–mass spectrometry analysis of antioxidant-enriched fraction prepared from P. tuberosa (Satpathy et al., 2020). We have listed various phytoconstituents isolated from P. tuberosa and provided detailed information about their chemical structures, IUPAC names, and pharmacological activities, as well as associated references, in Table 2. The chemical structures of phytochemical compounds from P. tuberosa were drawn using “ChemDraw JS 19.0”; https://chemdrawdirect.perkinelmer.cloud/js. IUPAC (International Union of Pure and Applied Chemistry) names have been taken from PubChem database.
TABLE 2. Pharmacological activities of phytoconstituents of Pueraria tuberosa.
Toxicology of Pueraria tuberosa
The acute (single dose of 2,000 and 5,000 mg/kg body weight) and repeated dose (250, 500, 1,000, and 2,000 mg/kg body weight for 28 days) toxicity studies with water extract of the tuber of P. tuberosa were conducted in rats as per OECD (Organization for Economic Co-Operation and Development) guidelines. The survival rate and biochemical and histological changes were studied. No adverse effect was reported in single-dose acute toxicity, but in repeated dose toxicity studies, 100% mortality was observed on day 21 at 2,000 mg/kg body weight, and histological examination of the visceral organs showed that this mortality could be due to hepatotoxicity (Pandey et al., 2018). However, histological evaluation of different organs using hematoxylin and eosin staining did not observe any morphological alterations in the spleen, adrenal glands, and heart. The size and shapes in crypts and villi of the intestine and semeniferous tubules were intact with normal spermatozoa count in testis (Pandey et al., 2019). In another experiment on acute toxicity study of poly-herbal formulation (containing P. tubrosa), “Dhatryadi Ghrita” methanolic extract did not show any untoward effects in mice (Pal and Mishra, 2019).
Conclusion and Future Directions
The scientific community worldwide has shown an interest in discovering the disease combating potential of natural flora and bioactive compounds therein. A wide pool of literature suggests that these phytochemicals hold the immense potential of eliminating diseases, and many such plant-based drugs have long been used in many parts of the world. Markedly, the tuber and leaf of P. tuberosa plant have been used from ancient times in the traditional practices. Previous literature has shown that leaf and tuber extracts of the plant contain several bioactive constituents that possess an extensive range of pharmacological activities. Some of the isolated compounds, namely, puerarin, irisolidone, genistein, daidzein, biochanin A, biochanin B, isoorientin, and mangiferin, have been studied for various medicinal purposes and demonstrated several pharmacological activities like anticancerous, antidiabetic, anti-inflammatory, antioxidant, antiviral, cardioprotective, fibrinolytic, hepatoprotective, hypolipidemic, immunomodulatory, neuroprotective, nephroprotective, nootropic, vasodilatory, and wound healing. The bioactive constituents of P. tuberosa can individually or synergistically exert their therapeutic effects. Apart from puerarin, daidzein, genistein, irisolidone, and biochanin, many more compounds have been identified from P. tuberosa; however, underlying mechanisms of action of compounds isolated from this plant are not completely known. Thus, exploration of pharmacological mechanisms of individual bioactive constituents and their toxicity/clinical studies shall be the focus of future investigations. The extensive range of pharmacological properties of P. tuberosa could provide us a new interesting path for future research and may present new perspectives for the disease management.
Author Contributions
RB was responsible for the methodology, writing the original draft, and data curation. BC and SR were responsible for data curation and reviewing and editing the manuscript. NK was responsible for conceptualization, data curation, writing, reviewing, and editing the manuscript.
Funding
RB was supported by CSIR-JRF fellowship, and NK lab was supported by grants from CSIR-IMTECH.
Conflict of Interest
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
The authors gratefully acknowledge the Foundation for Revitalization of Local Health Traditions and the University of TransDisciplinary Health Sciences and Technology (FRLHT-TDU) for providing the permission to use images of P. tuberosa plant from Indian Medicinal Plants database.
References
Adedapo, A. A., Fagbohun, O. A., Dawurung, C., Oyagbemi, A. A., Omobowale, T. O., and Yakubu, M. A. (2017). The aqueous tuber extract of Pueraria tuberosa (Willd.) D.C. caused cytotoxic effect on HT 29 cell lines with down regulation of nuclear factor-kappa B (NF-κB). J. Compl. Integr. Med. 16 (4), 1–8. doi:10.1515/jcim-2016-0119
Ali, H., Dixit, S., Ali, D., Alqahtani, S. M., Alkahtani, S., and Alarifi, S. (2015). Isolation and evaluation of anticancer efficacy of stigmasterol in a mouse model of DMBA-induced skin carcinoma. Drug Des. Dev. Ther. 9, 2793–2800. doi:10.2147/DDDT.S83514
Amalan, V., Vijayakumar, N., Indumathi, D., and Ramakrishnan, A. (2016). Antidiabetic and antihyperlipidemic activity of p-coumaric acid in diabetic rats, role of pancreatic GLUT 2: in vivo approach. Biomed. Pharmacother. 84, 230–236. doi:10.1016/j.biopha.2016.09.039
Anilkumar, K., Reddy, G. V., Azad, R., Sastry Yarla, N., Dharmapuri, G., Srivastava, A., et al. (2017). Evaluation of anti-inflammatory properties of isoorientin isolated from tubers of pueraria tuberosa. Oxid. Med. Cell. Longev. 2017, 1–7. doi:10.1155/2017/5498054
Aruna, M. R., Kumar, D. J. M., Senbagam, D., and Senthilkumar, B. (2016). Investigation on phytochemical and antimicrobial properties of tuber extracts of pueraria tuberosa linn. J. Pure Appl. Microb. 10 (2), 1573–1578.
Aruna, M. R., Mukesh Kumar, D. J., Palani, P., Senbagam, D., and Senthilkumar, B. (2018). Effects of pueraria tuberosa linn hydroalcoholic tuber extract on expression of apoptosis associated proteins in HT-29 human colon carcinoma cell line. Int. J. Curr. Microbiol. Appl. Sci. 7 (6), 3863–3873. doi:10.20546/ijcmas.2018.706.455
Ayurvedic pharmacopoeia of India (1999). Ayurvedic pharmacopoeia of India.Part-1, 2. New Delhi, India: Ministry of Health and Family Planning, Department of Health, Government of India, 1–190.
Ayurvedic pharmacopoeia of India (2001). Ayurvedic pharmacopoeia of India Part-1., 2. New Delhi, India: Ministry of Health and Family Planning, Department of Health, Government of India, 183–184.
Babu, P. V., Bandi, S., Raju, M., and Tiwari, V. K. (2016). Antioxidant and immunosuppressant activity of pueraria tuberosa. IJPPR. 8 (1), 23–34.
Bagheri, M., Joghataei, M. T., Mohseni, S., and Roghani, M. (2011). Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer's disease. Neurobiol. Learn. Mem. 95 (3), 270–276. doi:10.1016/j.nlm.2010.12.001
Basavaraj, P., Shivakumar, B., and Shivakumar, H. (2011). Evaluation of anticonvulsant activity of alcoholic extract of tubers of Pueraria tuberosa (Roxb). Adv. in Pharm. and Toxicol. 12 (I), 1–9.
Berköz, M., Krośniak, M., Özkan-Yılmaz, F., and Özlüer-Hunt, A. (2020). Prophylactic effect of Biochanin A in lipopolysaccharide-stimulated BV2 microglial cells. Immunopharmacol. Immunotoxicol. 1. doi:1010.1080/08923973.2020.1769128
Bhattarai, G., Min, C. K., Jeon, Y. M., Bashyal, R., Poudel, S. B., Kook, S. H., et al. (2019). Oral supplementation with p-coumaric acid protects mice against diabetes-associated spontaneous destruction of periodontal tissue. J. Periodontal. Res. 54 (6), 690–701. doi:10.1111/jre.12678
Bulugonda, R. K., Kumar, K. A., Gangappa, D., Beeda, H., Philip, G. H., Muralidhara Rao, D., et al. (2017). Mangiferin from Pueraria tuberosa reduces inflammation via inactivation of NLRP3 inflammasome. Sci. Rep. 7, 42683–42714. doi:10.1038/srep42683
Cha, H., Lee, S., Lee, J. H., and Park, J. W. (2018). Protective effects of p-coumaric acid against acetaminophen-induced hepatotoxicity in mice. Food Chem. Toxicol. 121, 131–139. doi:10.1016/j.fct.2018.08.060
Chauhan, N. S., Sharma, V., Thakur, M., Christine Helena Frankland Sawaya, A., and Dixit, V. K. (2013). Pueraria tuberosa DC extract improves androgenesis and sexual behavior via FSH LH cascade. Sci. World. J. 2013, 1–10. doi:10.1155/2013/780659
Chen, X., He, Z., Wu, X., Mao, D., Feng, C., Zhang, J., et al. (2020). Comprehensive study of the interaction between Puerariae Radix flavonoids and DNA: from theoretical simulation to structural analysis to functional analysis. Spectrochim. Acta Mol. Biomol. Spectrosc. 231. doi:10.1016/j.saa.2020.118109
Choi, E. J., and Kim, G. H. (2014). The antioxidant activity of daidzein metabolites, O‑desmethylangolensin and equol, in HepG2 cells. Mol. Med. Rep. 9 (1), 328–332. doi:10.3892/mmr.2013.1752
Choi, E. M., Suh, K. S., Park, S. Y., Chin, S. O., Rhee, S. Y., and Chon, S. (2019). Biochanin A prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced adipocyte dysfunction in cultured 3T3-L1 cells. J. Environ. Sci. Heal. 54 (9), 865–873. doi:10.1080/10934529.2019.1603746
Choi, Y. R., Shim, J., and Kim, M. J. (2020). Genistin: a novel potent anti-adipogenic and anti-lipogenic agent. Molecules 25 (9). doi:10.3390/molecules25092042
Croom, E. M. (2004). Pueraria. The Genus pueraria. Econ. Bot. 58 (3), 490. doi:10.1663/0013-0001(2004)058[0490:dfabre]2.0.co;2
Dalal, P. K., Tripathi, A., and Gupta, S. K. (2013). Vajikarana: treatment of sexual dysfunctions based on Indian concepts. Indian J. Psych. 55, S273. doi:10.4103/0019-5545.105550
De Luca, V., Salim, V., Atsumi, S. M., and Yu, F. (2012). Mining the biodiversity of plants: a revolution in the making. Science 336 (6089), 1658–1661. doi:10.1126/science.1217410
Dey, D., Pal, B. C., Biswas, T., Roy, S. S., Bandyopadhyay, A., Mandal, S. K., et al. (2007). A lupinoside prevented fatty acid induced inhibition of insulin sensitivity in 3T3 L1 adipocytes. Mol. Cell. Biochem. 300 (1–2), 149–157. doi:10.1007/s11010-006-9378-1
Dos Santos Morais, M. L. G., de Brito, D. C. C., Pinto, Y., Mascena Silva, L., Montano Vizcarra, D., Silva, R. F., et al. (2019). Natural antioxidants in the vitrification solution improve the ovine ovarian tissue preservation. Reprod. Biol. 19 (3), 270–278. doi:10.1016/j.repbio.2019.07.008
El-Bakoush, A., and Olajide, O. A. (2018). Formononetin inhibits neuroinflammation and increases estrogen receptor beta (ERβ) protein expression in BV2 microglia. Int. Immunopharm. 61, 325–337. doi:10.1016/j.intimp.2018.06.016
Elmarakby, A. A., Ibrahim, A. S., Faulkner, J., Mozaffari, M. S., Liou, G. I., and Abdelsayed, R. (2011). Tyrosine kinase inhibitor, genistein, reduces renal inflammation and injury in streptozotocin-induced diabetic mice. Vasc. Pharmacol. 55 (5–6), 149–156. doi:10.1016/j.vph.2011.07.007
Fu, X., Qin, T., Yu, J., Jiao, J., Ma, Z., Fu, Q., et al. (2019). Formononetin ameliorates cognitive disorder via PGC-1α pathway in neuroinflammation conditions in high-fat diet-induced mice. CNS Neurol. Disord. - Drug Targets 18 (7), 566–577. doi:10.2174/1871527318666190807160137
Gindi, S., Awen, B. Z., Baburao, C., and Khagga, M. (2010). Anti ulcerogenic & ulcer healing studies of aqueous extract of Pueraria tuberosa leaves on rats. Int. J. Pharma Bio Sci. 1 (4), 651–661.
Gu, M., Zheng, A. B., Jin, J., Cui, Y., Zhang, N., Che, Z. P., et al. (2016). Cardioprotective effects of genistin in rat myocardial ischemia-reperfusion injury studies by regulation of P2X7/NF-κB pathway. Evid. Based Complement Alternat. Med. 2016, 5381290. doi:10.1155/2016/5381290
Guo, C. J., Xie, J. J., Hong, R. H., Pan, H. S., Zhang, F. G., and Liang, Y. M. (2019). Puerarin alleviates streptozotocin (STZ)-induced osteoporosis in rats through suppressing inflammation and apoptosis via HDAC1/HDAC3 signaling. Biomed. Pharmacother. 115, 108570. doi:10.1016/j.biopha.2019.01.031
Gupta, R. S., Sharma, R., Sharma, A., Choudhary, R., Bhatnager, A. K., Joshi, Y. C., et al. (2005). Antifertility effects of Puerariaï¿¿tuberosa. Root extract in male rats. Pharmaceut. Biol. 42 (8), 603–609. doi:10.1080/13880200490902491
Han, N. R., Kim, H. M., and Jeong, H. J. (2015). The potential anti-proliferative effect of β-sitosterol on human mast cell line-1 cells. Can. J. Physiol. Pharmacol. 93 (11), 979–983. doi:10.1139/cjpp-2015-0166
He, Y., Wu, X., Cao, Y., Hou, Y., Chen, H., Wu, L., et al. (2016). Daidzein exerts anti-tumor activity against bladder cancer cells via inhibition of FGFR3 pathway. Neoplasma. 63 (4), 523–531. doi:10.4149/neo_2016_405
Heinrich, M., Appendino, G., Efferth, T., Fürst, R., Izzo, A. A., Kayser, O., et al. (2020). Best practice in research - overcoming common challenges in phytopharmacological research. J. Ethnopharmacol. 246, 112230. doi:10.1016/j.jep.2019.112230
Hua, F., Li, C. H., Chen, X. G., and Liu, X. P. (2018). Daidzein exerts anticancer activity towards SKOV3 human ovarian cancer cells by inducing apoptosis and cell cycle arrest, and inhibiting the Raf/MEK/ERK cascade. Int. J. Mol. Med. 41 (6), 3485–3492. doi:10.3892/ijmm.2018.3531
Huang, D., Wang, C., Duan, Y., Meng, Q., Liu, Z., Huo, X., et al. (2017). Targeting Oct2 and P53: formononetin prevents cisplatin-induced acute kidney injury. Toxicol. Appl. Pharmacol. N. 326, 15–24. doi:10.1016/j.taap.2017.04.013
Huang, Z., Liu, Y., and Huang, X. (2018). Formononetin may protect aged hearts from ischemia/reperfusion damage by enhancing autophagic degradation. Mol. Med. Rep. 18 (6), 4821–4830. doi:10.3892/mmr.2018.9544
Hwang, J. S., Kang, E. S., Han, S. G., Lim, D. S., Paek, K. S., Lee, C. H., et al. (2018). Formononetin inhibits lipopolysaccharideinduced release of high mobility group box 1 by upregulating SIRT1 in a PPARδ-dependent manner. Peer J. 6 (1, e4208). doi:10.7717/peerj.4208
Indian Medicinal Plant Database Foundation for Revitalisation of Local Health Traditions (FRLHT). Available at: http://www.medicinalplants.in/searchpage/showdetails/xplant_id/5e61a3ccb898ce34f62ec050b012b2f2/keywords/vidari/languages/HI.
Janeesh, P. A., and Abraham, A. (2014). Robinin modulates doxorubicin-induced cardiac apoptosis by TGF-β1 signaling pathway in Sprague Dawley rats. Biomed. Pharmacother. 68 (8), 989–998. doi:10.1016/j.biopha.2014.09.010
Janeesh, P. A., Sasikala, V., Dhanya, C. R., and Abraham, A. (2014). Robinin modulates TLR/NF-κB signaling pathway in oxidized LDL induced human peripheral blood mononuclear cells. Int. Immunopharm. 18 (1), 191–197. doi:10.1016/j.intimp.2013.11.023
Jang, H. M., Park, K. T., Noh, H. D., Lee, S. H., and Kim, D. H. (2019). Kakkalide and irisolidone alleviate 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice by inhibiting lipopolysaccharide binding to toll-like receptor-4 and proteobacteria population. Int. Immunopharm. 73, 246–253. doi:10.1016/j.intimp.2019.05.008
Jiang, K., Chen, H., Tang, K., Guan, W., Zhou, H., Guo, X., et al. (2018). Puerarin inhibits bladder cancer cell proliferation through the mTOR/p70S6K signaling pathway. Oncol Lett. 15 (1), 167–174. doi:10.3892/ol.2017.7298
Kambhoja, S., and Murthy, K. R. K. (2007). Wound healing and anti-inflammatory activity of Pueraria tuberosa (Roxb Ex wild) DC. Biomed. 2 (2), 229–232.
Kang, G. D., Lee, S. Y., Jang, S. E., Han, M. J., and Kim, D. H. (2017). Irisolidone attenuates ethanol-induced gastric injury in mice by inhibiting the infiltration of neutrophils. Mol. Nutr. Food Res. 61 (2). doi:10.1002/mnfr.201600517
Kanter, M., Tuncer, I., Erboga, M., Atanassova, P., Takir, M., and Kostek, O. (2016). The effects of quercetin on liver regeneration after liver resection in rats. Folia Morphol. 75 (2), 179–187. doi:10.5603/FM.a2015.0086
Keung, W. M. (2002). Pueraria. The Genus pueraria. Boca Raton, FL: CRC Press. doi:10.1201/9780203300978
Kim, H. B., Lee, S., Hwang, E. S., Maeng, S., and Park, J. H. (2017). p-Coumaric acid enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments. Biochem. Biophys. Res. Commun. 492 (3), 493–499. doi:10.1016/j.bbrc.2017.08.068
Kim, K. A., Lee, I. A., Gu, W., Hyam, S. R., and Kim, D. H. (2014). β-Sitosterol attenuates high-fat diet-induced intestinal inflammation in mice by inhibiting the binding of lipopolysaccharide to toll-like receptor 4 in the NF-κB pathway. Mol. Nutr. Food Res. 58 (5), 963–972. doi:10.1002/mnfr.201300433
Kim, M., Choi, Y., Lee, J., Kim, K., and Yang, W. M. (2016). Topical treatment of hair loss with formononetin by modulating apoptosis. Planta Med. 82 (1–2), 65–69. doi:10.1055/s-0035-1557897
Kirtikar, K. R., and Basu, B. D. (1935). Indian medicinal plants. Allahabad, India: Allahabad Lalit Mohan Basu.
Kumar, P. G. (2016). Wild edible plants of Hassan District, Karnataka: a role in ayurvedic formulation. Int. J. Herb. Med. 4 (1), 16–24.
Kumawat, R. B., Sharma, R. A., Mali, P. C., and Chandrawat, P. (2017). Ethnophormacological screening of some selected medicinal plants. Res. J. Recent Sci. 6 (5), 32–41.
Lee, H., Lee, D., Kang, K. S., Song, J. H., and Choi, Y. K. (2018). Inhibition of intracellular ROS accumulation by formononetin attenuates cisplatin-mediated apoptosis in LLC-PK1 cells. Int. J. Mol. Sci. 19 (3). doi:10.3390/ijms19030813
legumes, Available at: http://www.legumes-online.net/ildis/aweb/td076/td_16078.htm (Accessed July 7, 2020).
Li, S.-C. (2003). Chinese medical herbs: a modern edition of a classic sixteenth-century manual. Mineola, NY: Dover Publications Inc.
Li, X., Zhu, Q., Zheng, R., Yan, J., Wei, M., Fan, Y., et al. (2020). Puerarin attenuates diabetic nephropathy by promoting autophagy in podocytes. Front. Physiol. 11. doi:10.3389/fphys.2020.00073
Li, Y. L., Guo, H., Zhao, Y. Q., Li, A. F., Ren, Y. Q., and Zhang, J. W. (2017). Quercetin protects neuronal cells from oxidative stress and cognitive degradation induced by amyloid β-peptide treatment. Mol. Med. Rep. 16 (2), 1573–1577. doi:10.3892/mmr.2017.6704
Likhitkar, M., and Pande, M. (2017). Antioxidant activity of methanolic and ethanolic extracts of Pueraria tuberosa plant. Int J Ind Herbs Drugs 2 (1), 1–5.
Liu, D., Zhen, W., Yang, Z., Carter, J. D., Si, H., and Reynolds, K. A. (2006). Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a cAMP-dependent protein kinase pathway. Diabetes 55 (4), 1043–1050. doi:10.2337/diabetes.55.04.06.db05-1089
Liu, X., Zhao, W., Wang, W., Lin, S., and Yang, L. (2017). Puerarin suppresses LPS-induced breast cancer cell migration, invasion and adhesion by blockage NF-κB and Erk pathway. Biomed. Pharmacother. 92, 429–436. doi:10.1016/j.biopha.2017.05.102
Luo, L., Zhou, J., Zhao, H., Fan, M., and Gao, W. (2019). The anti-inflammatory effects of formononetin and ononin on lipopolysaccharide-induced zebrafish models based on lipidomics and targeted transcriptomics. Metabolomics 15 (12, 153). doi:10.1007/s11306-019-1614-2
Maji, A. K., Pandit, S., Banerji, P., and Banerjee, D. (2014). Natural product research., 28. Abingdon, UK: Taylor & Francis, 2111–2127. doi:10.1080/14786419.2014.928291
Maji, A. K., Mahapatra, S., and Banerjee, D. (2014). In-vivo immunomodulatory potential of standardized pueraria tuberosa extract and its isoflavonoids. Int. J. Pharm. Pharmaceut. Sci. 6 (1), 861–867.
Mhaske, H. P., Vaidya, V. V., Kekare, M. B., Champanerkar, P. A., and Parekh, S. A. (2009). Quantification of {β-sitosterol and puerarin from Pueraria tuberosa DC. by using high performance thin layer chromatography. Asian J. Chem. 21 (5), 3449–3454.
Migkos, T., Pourová, J., Vopršalová, M., Auger, C., Schini-Kerth, V., and Mladěnka, P. (2020). Biochanin A, the most potent of 16 isoflavones, induces relaxation of the coronary artery through the calcium channel and cGMP-dependent pathway. Planta Med. 86 (10), 708–716. doi:10.1055/a-1158-9422
Nagwani, S., and Tripathi, Y. B. (2010). Amelioration of cisplatin induced nephrotoxicity by PTY: a herbal preparation. Food Chem. Toxicol. 48 (8–9), 2253–2258. doi:10.1016/j.fct.2010.05.057
National Medicinal Plants Board, Government of India Retrieved from https://www.nmpb.nic.in/about-us July 7, 2020).
Navaneethan, D., and Rasool, M. (2014). p-Coumaric acid, a common dietary polyphenol, protects cadmium chloride-induced nephrotoxicity in rats. Ren. Fail. 36 (2), 244–251. doi:10.3109/0886022X.2013.835268
Neog, M. K., Joshua Pragasam, S., Krishnan, M., and Rasool, M. (2017). p-Coumaric acid, a dietary polyphenol ameliorates inflammation and curtails cartilage and bone erosion in the rheumatoid arthritis rat model. Biofactors 43 (5), 698–717. doi:10.1002/biof.1377
Oza, M. J., and Kulkarni, Y. A. (2018b). Biochanin A improves insulin sensitivity and controls hyperglycemia in type 2 diabetes. Biomed. Pharmacother. 107, 1119–1127. doi:10.1016/j.biopha.2018.08.073
Oza, M. J., and Kulkarni, Y. A. (2019). Formononetin attenuates kidney damage in type 2 diabetic rats. Life Sci. 219, 109–121. doi:10.1016/j.lfs.2019.01.013
Oza, M. J., and Kulkarni, Y. A. (2018a). Formononetin treatment in type 2 diabetic rats reduces insulin resistance and hyperglycemia. Front. Pharmacol. 9, 73. doi:10.3389/fphar.2018.00739
Pal, R. S., and Mishra, A. (2019). Evaluation of acute toxicity of the methanolic extract of dhatryadi ghrita in wistar rats. Open Pharmacol. J. 9 (1), 1–4. doi:10.2174/1874143601909010001
Palanisamy, N., and Venkataraman, A. C. (2013). Beneficial effect of genistein on lowering blood pressure and kidney toxicity in fructose-fed hypertensive rats. Br. J. Nutr. 109 (10), 1806–1812. doi:10.1017/S0007114512003819
Pandey, H., Srivastava, S., Singh, S., and Tripathi, Y. B. (2019). Histopathological study of different organs of charles foster strain rat under the exposure of Pueraria tuberosa. BioRxiv. 671529. doi:10.1101/671529
Pandey, H., Srivastava, S., and Tripathi, Y. B. (2019). Herbal tablet of Pueraria tuberosa water extract suppresses the alloxan induced liver damage and hyperglycemia in rats. BioRxiv. 671594. doi:10.1101/671594
Pandey, H., Srivastava, S., Tripathi, Y. B., and Kumar, R. (2018). Preclinical acute and repeated dose toxicity of Pueraria tuberosa (PTWE) on charles foster rats. Int. J. Pharmaceut. Sci. Res. 9 (11), 4572. doi:10.13040/IJPSR.0975-8232.9(11).4572-81
Pandey, N., and Tripathi, Y. B. (2010). Antioxidant activity of tuberosin isolated from Pueraria tuberose Linn. J. Inflamm. 7, 47. doi:10.1186/1476-9255-7-47
Pandey, N., Chaurasia, J. K., Tiwari, O. P., and Tripathi, Y. B. (2007). Antioxidant properties of different fractions of tubers from Pueraria tuberosa Linn. Food Chem. 105 (1), 219–222. doi:10.1016/j.foodchem.2007.03.072
Pandya, K. B., Patel, H. B., Bhatt, P. R., Patel, U. D., and Modi, C. M. (2019). In vitro antibacterial activity of sixteen medicinal plants collected from nearby region of Junagadh, Gujarat (India). J. Pharm. Innov. 8 (3), 662–667.
Park, C. E., Yun, H., Lee, E. B., Min, B. I., Bae, H., Choe, W., et al. (2010). The antioxidant effects of genistein are associated with AMP-activated protein kinase activation and PTEN induction in prostate cancer cells. J. Med. Food. 13 (4), 815–820. doi:10.1089/jmf.2009.1359
Patel, J., Doshi, N., Bhalerao, A., and Bonagiri, R. (2016). Immunomodulatory activity of ethanolic extract of Pueraria Tuberosa Immunomodulatory activity of ethanolic extract of Pueraria Tuberosa D.C. Int. J. Sci. Eng. Res. 7 (11), 708–713.
Patel, R. V., Mistry, B. M., Shinde, S. K., Syed, R., Singh, V., and Shin, H. S. (2018). Therapeutic potential of quercetin as a cardiovascular agent. Eur. J. Med. Chem. 155, 889–904. doi:10.1016/j.ejmech.2018.06.053
Pragasam, S. J., Venkatesan, V., and Rasool, M. (2013). Immunomodulatory and anti-inflammatory effect of p-coumaric acid, a common dietary polyphenol on experimental inflammation in rats. Inflammation 36 (1), 169–176. doi:10.1007/s10753-012-9532-8
Pramanik, S. S., Sur, T. K., Debnath, P. K., and Bhattacharyya, D. (2010). Effect of Pueraria tuberosa tuber extract on chronic foot shock stress in Wistar rats, Nepal Med. Coll. J. 12 (4), 234–238.
Pramanik, S. S., Sur, T. K., Debnath, P. K., Pramanik, T., and Bhattacharyya, D. (2011). Effect of Pueraria tuberosa on cold immobilization stress induced changes in plasma corticosterone and brain monoamines in rats. J. Nat. Remedies. 11 (1), 69–75. doi:10.18311/jnr/2011/52
Pueraria tuberosa-Vikaspedia Available at: https://vikaspedia.in/agriculture/crop-production/package-of-practices/medicinal-and-aromatic-plants/pueraria-tuberosa.(Retrieved from September 21 2020).
Puri, H. S. (2003). Rasayana: Ayurvedic Herbs for Longevity and Rejuvenation. 3 (2), (Hoboken, NJ: CRC Press). 303–307.
Qian, Y., Guan, T., Huang, M., Cao, L., Li, Y., Cheng, H., et al. (2012). Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model. Neurochem. Int. 60 (8), 759–767. doi:10.1016/j.neuint.2012.03.011
Qiu, G., Tian, W., Huan, M., Chen, J., and Fu, H. (2017). Formononetin exhibits anti-hyperglycemic activity in alloxan-induced type 1 diabetic mice. Exp. Biol. Med. 242 (2), 223–230. doi:10.1177/1535370216657445
Raghuwanshi, R., and Jain, B. (2011). Hypoglycemic effect of Pueraria tuberosa tubers in healthy and alloxan diabetic Rats. J. Chem. Biol. Phys. Sci. 2 (1), 270–272.
Rani, V. U., Sudhakar, M., and Ramesh, A. (2017). Protective effect of Pueraria tuberosa Linn. in arsenic induced nephrotoxicity in rats. Asian J. Pharmaceut. Res. 7 (1), 15. doi:10.5958/2231-5691.2017.00003.x
Rao, N. V., Pujar, B., Nimbal, S. K., Shantakumar, S. M., and Satyanarayana, S. (2008). Nootropic activity of tuber extract of Pueraria tuberosa (roxb). Indian J. Exp. Biol. 46 (8), 591–598.
Ratnam, V., and Venkata Raju, R. R. (2009). Preliminary phytochemical and antimicrobial properties of pueraria tuberosa (Willd.) DC: a potential medicinal plant. Ethnobotanical Leaflets. 13, 1051–1059.
Rawtal, B., Sahatpure, N., and Sakharwade, S. (2019). Pueraria tuberosa (vidarikanda): an emerging cosmeceutical herb. Int. J. Sci. 4 (7), 130–137.
Robinson, M. M., and Zhang, X. (2011). The world medicines situation 2011, traditional Medicines : global situation , issues and challenges. 3rd Edn. (Geneva, Switzerland: World Health Organization), 1–14.
Roy, A. J., and Stanely Mainzen Prince, P. (2013). Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Food Chem. Toxicol. 60, 348–354. doi:10.1016/j.fct.2013.04.052
Sabitha, R., Nishi, K., Gunasekaran, V. P., Agilan, B., David, E., Annamalai, G., et al. (2020). p-Coumaric acid attenuates alcohol exposed hepatic injury through MAPKs, apoptosis and Nrf2 signaling in experimental models. Chem. Biol. Interact. 321, 109044. doi:10.1016/j.cbi.2020.109044
Sadguna, V., Sarikha, K., Komuraiah, T. R., and Mustafa, M. (2015). Anti-microbial activity of pueraria tuberosa DC, an economically and medicinally important plant. Int. J. Curr. Microbiol. App. Sci. 4 (5), 152–159 Available at: https://www.ijcmas.com/vol-4-5.
Sakamoto, Y., Naka, A., Ohara, N., Kondo, K., and Iida, K. (2014). Daidzein regulates proinflammatory adipokines thereby improving obesity-related inflammation through PPARγ. Mol. Nutr. Food Res. 58 (4), 718–726. doi:10.1002/mnfr.201300482
Sakamula, R., and Thong-asa, W. (2018). Neuroprotective effect of p-coumaric acid in mice with cerebral ischemia reperfusion injuries. Metab. Brain Dis. 33 (3), 765–773. doi:10.1007/s11011-018-0185-7
Satpathy, S., Patra, A., Ahirwar, B., and Hussain, M. D. (2018). Antioxidant and anticancer activities of green synthesized silver nanoparticles using aqueous extract of tubers of Pueraria tuberosa. Artificial Cells. Nanomed. and Biotechnol. 46 (Suppl. 3), S71–S85. doi:10.1080/21691401.2018.1489265
Satpathy, S., Patra, A., Hussain, M. D., and Ahirwar, B. (2017). Simultaneous estimation of genistein and daidzein in Pueraria tuberosa (Willd.) DC by validated high-performance thin-layer chromatography (HPTLC) densitometry method. J. Liq. Chromatogr. Relat. Technol. 40 (10), 499–505. doi:10.1080/10826076.2017.1329743
Satpathy, S., Patra, A., Hussain, M. D., and Kazi, M. (2020). Antioxidant enriched fraction from Pueraria tuberosa alleviates ovariectomized-induced osteoporosis in rats, and inhibits growth of breast and ovarian cancer cell lines in vitro. BioRxiv. doi:10.1101/2020.09.21.305953
Sawale, P. D., Singh, R. R. B., Kapila, S., Arora, S., Rastogi, S., and Rawat, A. K. S. (2013). Immunomodulatory and antioxidative potential of herb (Pueraria tuberosa) in mice using milk as the carrier. Int. J. Dairy Technol. 66 (2), 202–206. doi:10.1111/1471-0307.12011
Sharma, S., Agrawal, M., and Lal, M. (2018). Cultivation of “vidarikand” (Pueraria tuberosa dc): a drug of potential importance. Int. J. Inf. Retr. Res. (IJIRR). 5 (5), 5460–5462.
Sharma, S. H., Rajamanickam, V., and Nagarajan, S. (2018). Antiproliferative effect of p-Coumaric acid targets UPR activation by downregulating Grp78 in colon cancer. Chem. Biol. Interact. 291, 16–28. doi:10.1016/j.cbi.2018.06.001
Sharmila, R., Sindhu, G., and Arockianathan, P. M. (2016). Nephroprotective effect of β-sitosterol on N-diethylnitrosamine initiated and ferric nitrilotriacetate promoted acute nephrotoxicity in Wistar rats. J. Basic Clin. Physiol. Pharmacol. 27 (5), 473–482. doi:10.1515/jbcpp-2015-0085
Shilpashree, V. K., Dang, R., and Das, K. (2015). Evaluation of phytochemical investigation and immunomodulatory activity of four different plant species of vidari by carbon clearance test on wister rats. Ann. Phytomed. 4 (1), 94–98.
Shukla, R., Banerjee, S., and Tripathi, Y. B. (2018a). Antioxidant and Antiapoptotic effect of aqueous extract of Pueraria tuberosa (Roxb. Ex Willd.) DC. On streptozotocin-induced diabetic nephropathy in rats. BMC Compl. Alternative Med. 18 (1), 156. doi:10.1186/s12906-018-2221-x
Shukla, R., Banerjee, S., and Tripathi, Y. B. (2018b). Pueraria tuberosa extract inhibits iNOS and IL-6 through suppression of PKC-α and NF-kB pathway in diabetes-induced nephropathy. J. Pharm. Pharmacol. 70 (8), 1102–1112. doi:10.1111/jphp.12931
Shukla, R., Pandey, N., Banerjee, S., Tripathi, Y. B., and Tripathi, Y. B. (2017). Effect of extract of Pueraria tuberosa on expression of hypoxia inducible factor-1α and vascular endothelial growth factor in kidney of diabetic rats. Biomed. Pharmacother. 93, 276. doi:10.1016/j.biopha.2017.06.045
Shukla, S., Jonathan, S., and Sharma, A. (1996). Protective action of butanolic extract of Pueraria tuberosa DC. against carbon tetrachloride induced hepatotoxicity in adult rats. Phytother Res. 10 (7), 608–609. doi:10.1002/(SICI)1099-1573(199611)10:7<608::AID-PTR842>3.0.CO;2-1
Srivastava, S., Pandey, H., Singh, S. K., and Tripathi, Y. B. (2019). Anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory conditions induced by PTY-2 against STZ-induced stress in islets. Biosci Trends 13 (5), 382–393. doi:10.5582/bst.2019.01181
Srivastava, S., Shree, P., Pandey, H., and Tripathi, Y. B. (2018). Incretin hormones receptor signaling plays the key role in antidiabetic potential of PTY-2 against STZ-induced pancreatitis. Biomed. Pharmacother. 97, 330–338. doi:10.1016/j.biopha.2017.10.071
Srivastava, S., Shree, P., and Tripathi, Y. B. (2017). Active phytochemicals of Pueraria tuberosa for DPP-IV inhibition: in silico and experimental approach. J. Diabetes Metab. Disord. 16 (1), 46. doi:10.1186/s40200-017-0328-0
Srivastava, S., Koley, T. K., Singh, S. K., and Tripathi, Y. B. (2015). The tuber extract of pueraria tuberosa Linn. competitively inhibits DPP-IV activity in normoglycemic rats. Int. J. Pharm. Pharmaceut. Sci. 7 (9), 227–231.
Sukhotnik, I., Moati, D., Shaoul, R., Loberman, B., Pollak, Y., and Schwartz, B. (2018). Quercetin prevents small intestinal damage and enhances intestinal recovery during methotrexate-induced intestinal mucositis of rats. Food Nutr. Res. 62. doi:10.29219/fnr.v62.1327
Sumalatha, M., Munikishore, R., Rammohan, A., Gunasekar, D., Kumar, K. A., Reddy, K. K., et al. (2015). Isoorientin, a selective inhibitor of cyclooxygenase-2 (COX-2) from the tubers of pueraria tuberosa. Nat Prod Commun. 10 (10), 1703–1704. doi:10.1177/1934578x1501001017
Tanaka, T., Moriyama, T., Kawamura, Y., and Yamanouchi, D. (2016). Puerarin suppresses macrophage activation via antioxidant mechanisms in a CaPO. J. Nutr. Sci. Vitaminol. 62, 425–431. doi:10.3177/jnsv.62.425
Tanna, I., Aghera, H., Ashok, B., and Chandola, H. (2012). Protective role of Ashwagandharishta and flax seed oil against maximal electroshock induced seizures in albino rats. Ayu. 33 (1), 114–118. doi:10.4103/0974-8520.100327
Tanwar, Y., Goyal, S., and Ramawat, K. (2008). Hypolipidemic effects of tubers of Indian kudzu (Pueraria tuberosa). J Herb Med Toxicol. 2, 21–25.
Tie, L., An, Y., Han, J., Xiao, Y., Xiaokaiti, Y., Fan, S., et al. (2013). Genistein accelerates refractory wound healing by suppressing superoxide and FoxO1/iNOS pathway in type 1 diabetes. JNB (J. Nutr. Biochem.). 24 (1), 88–96. doi:10.1016/j.jnutbio.2012.02.011
Tripathi, A. K., and Kohli, S. (2013). Anti-diabetic activity and phytochemical screening of crude extracts of PuerariaTuberosa DC. (FABACEAE) grown in India on STZ -induced diabetic rats. Asian J. Med. Pharmaceut. Res. 3 (3), 66–73.
Tripathi, Y. B., and Aditi, P. (2020). Antioxidative and hypolipidemic effect of pueraria tuberosa water extract (ptwe) in rats with high fat diet induced non-alcoholic fatty liver disease (nafld). Int. J. Pharmaceut. Sci. Res. 11 (1), 378–386. doi:10.1017/CBO9781107415324.004
Tripathi, Y. B., Nagwani, S., Mishra, P., Jha, A., and Rai, S. P. (2012). Protective effect of Pueraria tuberosa DC. Embedded biscuit on cisplatin-induced nephrotoxicity in mice. J. Nat. Med. 66 (1), 109–118. doi:10.1007/s11418-011-0559-1
Tripathi, Y. B., Shukla, R., Pandey, N., Pandey, V., and Kumar, M. (2017). An extract of Pueraria tuberosa tubers attenuates diabetic nephropathy by upregulating matrix metalloproteinase-9 expression in the kidney of diabetic rats. J. Diabetes. 9 (2), 123–132. doi:10.1111/1753-0407.12393
Tripathi, Y., Pandey, N., Yadav, D., and Pandey, V. (2013). Anti-inflammatory effect of Pueraria tuberosa extracts through improvement in activity of red blood cell anti-oxidant enzymes. AYU. 34 (3), 297. doi:10.4103/0974-8520.123131
Umarani, V., Sudhakar, M., Ramesh, A., Lakshmi, B. V. S., and Sandhyarani, D. (2016). Protective effect of hydroalcoholic extract of Pueraria tuberosa against arsenic induced neurotoxicity in rats. Int. J. Res. Pharm. Chem. 6 (2), 350–362.
Vaishnav, K., Goyal, S., and Ramawat, K. G. (2006). Isoflavonoids production in callus culture of Pueraria tuberosa, the Indian kudzu. Indian J. Exp. Biol. 44 (12), 1012–1017.
Verma, S. K., Jain, V., and Singh, D. P. (2012). Effect of Pueraria tuberosa DC. (Indian Kudzu) on blood pressure, fibrinolysis and oxidative stress in patients with stage 1 hypertension. Pakistan J. Biol. Sci. 15 (15), 742–747. doi:10.3923/pjbs.2012.742.747
Verma, S. K., Jain, V., Vyas, A., and Singh, D. P. (2009). Protection against stress induced myocardial ischemia by Indian kudzu (Pueraria tuberosa)-a case study. Int. J. Herb. Med. 3 (1), 59–63.
Viji, Z., and Paulsamy, S. (2018). Preliminary phytochemical screening and HPTLC finger printing analysis of traditional medicinal plant Pueraria tuberosa (Roxb. ex Willd.) DC. Kong. Res. J. 5 (1), 56–59. doi:10.26524/krj254
Viji, Z., and Paulsamy, S. (2015). In-Vitro antioxidant properties and total phenolic, flavonoid and tannin contents of Pueraria tuberosa (Roxb. Ex Willd.) DC. RJPBCS. 7 (2428), 2428–2438.
Wang, H., Zhang, D., Ge, M., Li, Z., Jiang, J., and Li, Y. (2015). Formononetin inhibits enterovirus 71 replication by regulating COX- 2/PGE2 expression. Virol. J. 12 (1). doi:10.1186/s12985-015-0264-x
Wang, X. S., Guan, S. Y., Liu, A., Yue, J., Hu, L. N., Zhang, K., et al. (2019). Anxiolytic effects of Formononetin in an inflammatory pain mouse model. Mol. Brain 12 (1). doi:10.1186/s13041-019-0453-4
Wang, Y., Zhao, H., Li, X., Wang, Q., Yan, M., Zhang, H., et al. (2019). Formononetin alleviates hepatic steatosis by facilitating TFEB-mediated lysosome biogenesis and lipophagy. J. Nutr. Biochem. 73. doi:10.1016/j.jnutbio.2019.07.005
Wu, D., Wu, K., Zhu, Q., Xiao, W., Shan, Q., Yan, Z., et al. (2018). Formononetin administration ameliorates dextran sulfate sodium-induced acute colitis by inhibiting NLRP3 inflammasome signaling pathway. Mediat. Inflamm. 2018, 9878120. doi:10.1155/2018/9878120
Xia, D. Z., Zhang, P. H., Fu, Y., Yu, W. F., and Ju, M. T. (2013). Hepatoprotective activity of puerarin against carbon tetrachloride-induced injuries in rats: a randomized controlled trial. Food Chem. Toxicol. 59, 90–95. doi:10.1016/j.fct.2013.05.055
Xing, G., Dong, M., Li, X., Zou, Y., Fan, L., Wang, X., et al. (2011). Neuroprotective effects of puerarin against beta-amyloid-induced neurotoxicity in PC12 cells via a PI3K-dependent signaling pathway. Brain Res. Bull. 85 (3–4), 212–218. doi:10.1016/j.brainresbull.2011.03.024
Xu, X., Zheng, N., Chen, Z., Huang, W., Liang, T., and Kuang, H. (2016). Puerarin, isolated from Pueraria lobata (Willd.), protects against diabetic nephropathy by attenuating oxidative stress. Gene 591 (2), 411–416. doi:10.1016/j.gene.2016.06.032
Yadav, D., Sharma, A., Srivastava, S., and Tripathi, Y. B. (2016b). Nephroprotective potential of standardized herbals described in Ayurveda: a comparative study. J. Chem. Pharmaceut. Res. 8 (8), 419–427.
Yadav, D., Kumar, M., and Tripathi, Y. B. (2016a). Methanolic extract of tubers of Pueraria tuberosa Linn. ameliorates glycerol induced acute kidney injury in rats. J. Chem. Pharmaceut. Res. 8 (2), 133–139.
Yadav, D., Pandey, V., Srivastava, S., Tripathi, Y. B., and Kumar, M. (2019). Methanolic extract of Pueraria tuberosa Linn ameliorates renal injury and oxidative stress in rats with alloxan-induced diabetes. J. emerg. technol. 6, 557–574.
Yang, S., Wei, L., Xia, R., Liu, L., Chen, Y., Zhang, W., et al. (2019). Formononetin ameliorates cholestasis by regulating hepatic SIRT1 and PPARα. Biochem. Biophys. Res. Commun. 512 (4), 770–778. doi:10.1016/j.bbrc.2019.03.131
Yin, M. S., Xu, S. H., Wang, Y., Jie, L., Zhang, Q., Zheng, W. M., et al. (2016). Methylamine irisolidone, a novel compound, increases total ATPase activity and inhibits apoptosis in vivo and in vitro. J. Asian Nat. Prod. Res. 18 (6), 562–575. doi:10.1080/10286020.2015.1133610
Yu, Q., Han, W., Zhu, Y., and Zhai, H. (2017). Effect of puerarin on type II diabetes mellitus with orthopaedic footwear. Pak. J. Pharm. Sci. 30 (5), 1899–1903.
Yu, X., Gao, F., Li, W., Zhou, L., Liu, W., and Li, M. (2020). Formononetin inhibits tumor growth by suppression of EGFR-Akt-Mcl-1 axis in non-small cell lung cancer. J. Exp. Clin. Canc. Res. 39 (1). doi:10.1186/s13046-020-01566-2
Yue, Y., Shen, P., Xu, Y., and Park, Y. (2019). p-Coumaric acid improves oxidative and osmosis stress responses in Caenorhabditis elegans. J. Sci. Food Agric. 99 (3), 1190–1197. doi:10.1002/jsfa.9288
Zhang, D., and Li, M. (2019). Puerarin prevents cataract development and progression in diabetic rats through Nrf2/HO-1 signaling. Mol. Med. Rep. 20 (2), 1017–1024. doi:10.3892/mmr.2019.10320
Zhang, J., Liu, L., Wang, J., Ren, B., Zhang, L., and Li, W. (2018). Formononetin, an isoflavone from Astragalus membranaceus inhibits proliferation and metastasis of ovarian cancer cells. J. Ethnopharmacol. 221, 91–99. doi:10.1016/j.jep.2018.04.014
Zhang, Q.-Y., Zheng, W., Gul Khaskheli, S., and Huang, W. (2019). In Vivo evaluation of tectoridin from puerariae flos on anti-alcoholism property in rats. Journal of Food and Nutrition Research 7 (6), 458–464. doi:10.12691/jfnr-7-6-8
Zhang, Y., Chen, C., and Zhang, J. (2019). Effects and significance of formononetin on expression levels of HIF-1α and VEGF in mouse cervical cancer tissue. Oncol. Lett. 18 (3), 2248–2253. doi:10.3892/ol.2019.10567
Zheng, W., Sun, R., Yang, L., Zeng, X., Xue, Y., and An, R. (2017). Daidzein inhibits choriocarcinoma proliferation by arresting cell cycle at G1 phase through suppressing ERK pathway in vitro and in vivo. Oncol. Rep. 38 (4), 2518–2524. doi:10.3892/or.2017.5928
Zhong, Y., Zhang, X., Cai, X., Wang, K., Chen, Y., and Deng, Y. (2014). Puerarin attenuated early diabetic kidney injury through down-regulation of matrix metalloproteinase 9 in streptozotocin-induced diabetic rats. PLoS One 9 (1). doi:10.1371/journal.pone.0085690
Keywords: in vivo studies, pharmacological properties, phytochemical constituents, traditional uses, Pueraria tuberosa
Citation: Bharti R, Chopra BS, Raut S and Khatri N (2021) Pueraria tuberosa: A Review on Traditional Uses, Pharmacology, and Phytochemistry. Front. Pharmacol. 11:582506. doi: 10.3389/fphar.2020.582506
Received: 12 July 2020; Accepted: 16 November 2020;
Published: 27 January 2021.
Edited by:
Lyndy Joy McGaw, University of Pretoria, South AfricaReviewed by:
Francis-Alfred Unuagbe Attah, University of Ilorin, NigeriaRavishankar Ramesh Patil, Amity Institute of Biotechnology, Amity University, India
Copyright © 2021 Bharti, Chopra, Raut and Khatri. 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: Neeraj Khatri, bmVlcmFqQGltdGVjaC5yZXMuaW4=