The Genus Alternanthera: Phytochemical and Ethnopharmacological Perspectives

Ethnopharmacological relevance: The genus Alternanthera (Amaranthaceae) comprises 139 species including 14 species used traditionally for the treatment of various ailments such as hypertension, pain, inflammation, diabetes, cancer, microbial and mental disorders.

Aim of the review: To search research gaps through critical assessment of pharmacological activities not performed to validate traditional claims of various species of Alternanthera. This review will aid natural product researchers in identifying Alternanthera species with therapeutic potential for future investigation.

Materials and methods: Scattered raw data on ethnopharmacological, morphological, phytochemical, pharmacological, toxicological, and clinical studies of various species of the genus Alternanthera have been compiled utilizing search engines like SciFinder, Google Scholar, PubMed, Science Direct, and Open J-Gate for 100 years up to April 2021.

Results: Few species of Alternanthera genus have been exhaustively investigated phytochemically, and about 129 chemical constituents related to different classes such as flavonoids, steroids, saponins, alkaloids, triterpenoids, glycosides, and phenolic compounds have been isolated from 9 species. Anticancer, antioxidant, antibacterial, CNS depressive, antidiabetic, analgesic, anti-inflammatory, and immunomodulator effects have been explored in the twelve species of the genus. A toxicity study has been conducted on 3 species and a clinical study on 2 species.

Conclusions: The available literature on pharmacological studies of Alternanthera species reveals that few species have been selected based on ethnobotanical surveys for scientific validation of their traditional claims. But most of these studies have been conducted on uncharacterized and non-standardized crude extracts. A roadmap of research needs to be developed for the isolation of new bioactive compounds from Alternanthera species, which can emerge out as clinically potential medicines.

Introduction

The family Amaranthaceae comprises 65 genera and about 850 species (Hundiwale et al., 2012; Chandrashekhar, 2019). These species are mainly distributed in tropical regions of the United States of America, Africa, and India. Amongst 65 genera and 850 species, only 17 genera and 50 species have been recorded to be found in India. The plants from this family include herbs, shrubs, and universal weeds. The genus Alternanthera, a significant delegate of the family Amaranthaceae was coined by by Forsskal in 1775. The genus Alternanthera comprises roughly 139 species which are distributed in India, China, Sri Lanka, the United States of America, and Africa (Figure 1). Though not complete and exhaustive, but phytochemical characterization was found to be reported that of Alternanthera sessilis (L.) R.Br. ex DC., Alternanthera philoxeroides (Mart.) Griseb., Alternanthera brasiliana (L.) Kuntze, Alternanthera hirtula (Mart.) R.E.Fr., Alternanthera praelonga A.St.-Hil., Alternanthera littoralis P.Beauv., Alternanthera bettzickiana (Regel) G.Nicholson, and Alternanthera pungens Kunth (Table 1 with complete details).

FIGURE 1

FIGURE 1. Commonly observed geographical distribution of Alternanthera species, indicated in dark orange.

TABLE 1

TABLE 1. Chemical constituents isolated from genus Alternanthera.

The present review emphasizes traditional uses, chemical constituents, pharmacological actions, clinical potential, and safety profile of Alternanthera species. The current work has been compiled to fulfill the following goals: 1) to explore if traditional claims of Alternanthera species have been scientifically justified by pharmacological and clinical studies, and also to assess critically if their mechanism of actions is established, 2) to explore whether detailed phytochemical investigations have been conducted to detect and isolate main/bioactive constitutes of various species, 3) to reveal whether appropriate analytical methods have been developed for standardization of plant materials based on marker compounds, 4) to analyze whether isolated compounds from Alternanthera species have potential to be developed as lead molecules unaltered or needs derivatization to develop semisynthetic drugs through proper SAR studies and 5) to check if the safety and toxicity profiles of Alternanthera species have been studied. The scattered raw data has been compiled from online databases such as SciFinder, Google Scholar, PubMed, Science Direct, and Open J-Gate for 100 years up to April 2021 and offline databases such as Aromatic Plants Abstract, scientific journals, and books from different libraries of National repute. Keywords selected were based on various species of Alternanthera genus, and different biological activities. The articles which were in English and available with full text were included. Manuscript written in non-English versions were excluded. A total of 156 articles related to Alternanthera genus were finally studied and cited. But the cross-sectional literature review led us to cover a total of around 500 articles in this review article. The review article is categorized into six sections: 1) morphology emphasizes morphological characters of different Alternanthera species; 2) ethnopharmacology covers traditional uses of different Alternanthera species; 3) phytoconstituents includes name and structure of chemicals constituents isolated from various species of the genus; 4) biological activities focus on different pharmacological activities reported in various species and presented in the table; 5) toxicity studies include scientific reports of toxicity studies of different Alternanthera species and 6) clinical studies describe clinical trials conducted on humans.

Morphology

The morphological profile of various species of the genus was found to be similar with some variations. A. brasiliana (L.) Kuntze (a perennial herb mainly distributed in Brazil) is prostrate, 7.5–45 cm long branches, introducing a round stem, long internodes, and swollen nodes, at which inverse leaves connect (Kumar S. et al., 2011). Branches are glabrous, two lines of hair, nodes frequently villous; leaves are 2.5–7.5 cm, considerably longer when developing in watery spots, rather plump, at some point indefinitely denticulate; flowers are white, found in the form of bunches; seeds are 1.25–1.5 mm, sub-orbicular.

A. denticulata R. Br. and A. nahui Heenan and de Lange comprise stem of 100 mm height and located in an upright position (Heenan et al., 2009). The uniform spreading of minute hairs is present on the stems of both plants. The dark green-colored leaves (length—30 mm and breadth—6 mm) of both plants are linear, entire, narrow, elliptic, denticulate margins, and oblong in appearance. The abaxial surface of the tepals (length: 2.0–4.2 mm) is described by keeled, a character that is presented at the base of mature and dried tepals.

A. philoxeroides (Mart.) Griseb., a perennial herb, has stems crawling or gliding rising towards pinnacle, establishing at the lower hubs, branched, empty, with a longitudinal hairy groove score on two inverse sides (Pulipati et al., 2015). The fresh and delicious stems can develop on a level plane and float on the outside of the water, framing pontoons, or structure tangled bunches that develop onto banks. The leaves are inverse two by two, with an unmistakable midrib, and ranges from 5–10 cm. The plant consists of leaf, lanceolate shape, intense pinnacle, whole edge, glabrous surface, graduate base, and short strong petiole.

A. pungens Kunth is a perennial herb with a stem of 10–15 cm long with hair. The leaves are green in color and ovate in a shape of about 0.5–4.5 cm long and 0.3–2 cm in width (Naidu, 2012). It is native to the Southern American continent generally found in South Carolina, Florida, and California spreading around the road sides (Gupta et al., 2012). In 1918 it was first reported in the Southern parts of India (Rao, 2000).

A. sessilis (L.) R.Br. ex DC. is a perennial herb with purple-colored and glabrous branches grown from the root bases about 50 cm in length (Anitha and Kanimozhi, 2012). The fresh leaves are shiny, 1.3–3.0 cm long and 0.5–1.0 cm wide however the leaves are bigger in wet living spaces, direct elliptic, oval or obovate, zenith adjusted and base cuneate. The blossoms are subtle, white, borne in little, axillary heads; bracts are obovate and 1 mm long. The bracteoles are shorter, persevering; subequal, and intense. Utricleare cordi-structure and are unequivocally compacted. The seeds are orbicular. The plant bears blossoms and natural products consistently.

Ethnopharmacology and Traditional Uses

The infusion of inflorescences of A. Brasiliana (L.) Kuntze with water is used in headaches, coughs, colds, and grippe (Hundiwale et al., 2012). The infusion of leaves with a cup of water has been used in the treatment of fever while a decoction of roots is used in diarrhea. Traditionally, the various plant parts (stems, leaves, flowers, roots) of A. caracasana Kunth have been used to treat dysentery, diarrhea, and fever. The infusion of the plant is used as lavage or beverage in the traditional system of medicines (Canales-Martínez et al., 2008). The aerial parts of A. Brasiliana (L.) Kuntze are indicated in the treatment of inflammation, pain, and various infections (Hundiwale et al., 2012). The leaves of A. ficoidea (L.) P.Beauv. has been used in the treatment of heart and cancer problems (Patil and Kore, 2019). A. littoralis P. Beauv. has a long tradition of use in the treatment of infectious and inflammatory diseases (Koolen et al., 2017). The old texts indicated the use of A. littoralis P. Beauv. in the treatment of inflammatory, infectious diseases (de Santana Aquino et al., 2015), viral infections, immunity problems, cancer, malaria, and diarrhea (Hundiwale et al., 2012; Sekar, 2012). A. nodiflora R.Br. has been in the treatment of skin, degenerative and microbial infections (Feka et al., 2014). A. paronychioides A.St.-Hil. has been used in the treatment of hyperuricemia, rheumatic arthritis, uremia, nephritis, gout, cystitis, diabetes, and systemic neuralgia in TCM (Wu et al., 2013). In Ayurveda, the syrup of the whole plant of A. philoxeroides (Mart.) Griseb. has been employed in the treatment of influenza (Hundiwale et al., 2012). The aqueous infusion of leaf and flower of A. porrigens (Jacq.) Kuntze has been recorded in old texts for the treatment of hepatic pain, kidney problems, and influenza. A. pungens Kunth has been employed as folk medicine in Argentina, commonly known as Yerba del pollo, recorded in the Pharmacopeia National Argentina (1978) for various medicinal purposes. It has been traditionally used in the treatment of swelling, nasopharyngeal infections, as a painkiller in labor pain, and also for lactation stimulus in veterinary-related cases (Burkill, 1985). It is also used in the treatment of gonorrhea (Semenya and Potgieter, 2014), menstrual disorder, miscarriage (Lucky and Diame, 2010) and to treat dysentery, cholera, and many parasitic diseases (Grønhaug et al., 2008; Guede et al., 2010). In Sudan, it is used in aqueous form for the treatment of cough. In Brazil, the aerial parts are used against grippe and vermifuge (Agra et al., 2007). It is used for crushing kidney stones or renal calculi in the form of decoction. The whole plant of A. sessilis (L.) R.Br. ex DC. has been used as green vegetable for maintain the nutrient balance in body (Astudillo-Vázquez et al., 2008). The roasted leaves and stems (p.o.) of A. sessilis (L.) R.Br. ex DC. have been in the treatment of stomach pain, ulcer, and gastric problems (Kumar S. M. et al., 2011). The aerial parts of A. sessilis (L.) R.Br. ex DC. have been used as a diuretic in the Ayurvedic system of medicines (Hundiwale et al., 2012). The leaves of A. sessilis (L.) R.Br. ex DC. are used as a diuretic, antipyretic and antiseptic and roots are used as amenorrhea, inflammations, ovarian diseases, and female sterility. The young shoots of A. sessilis (L.) R.Br. ex DC. have been used as lactagogue and febrifuge (Hosamani et al., 2004). Keeping these in mind, the most common traditional uses for the Alternanthera species were recorded for the treatment and management of inflammation, pain, infectious diseases, and gastric problems.

Phytoconstituents Isolated and Identified in Alternanthera Species

GC–MS of n-hexane extract of A. philoxeroides (Mart.) Griseb. leaves showed the presence of 25 compounds. Among this Acetic acid, 2-(2-methoxycarbonylamino-5-nitrophenylthio)-, methyl ester (31.92%); 1,4-Benzenediol, 2,5-bis(1,1-dimethylethyl) (15.06%); 4-Pyridinecarboxamide, 6-bromo-4,5-dicyano-1,2,3,4-tetrahydro-3,3-dimethyl-2-[[(1methylethyamino] oxy] (8.53%); L-Cysteine, N-(trifluoroacetyl)-, butyl ester, trifluoroacetate (ester) (6.59%); Cyclopentaneundecanoic acid, methyl ester (5.4%) and 3-Bromo-N-(2-thiazolyl) benzamide (3.49%) are dominant (Akbar et al., 2021). LC-MS/MS and GC-MS analysis of an ethanolic extract of A. brasiliana (L.) Kuntze aerial parts were performed (Alencar Filho et al., 2019). Five compounds (luteolin-8-C-rhamnosylglucoside, 2″-O-rhamnosylvitexin, 2″-O-rhamnosyl-6-C-glucosyl methyl-luteolin, rutin, and 2″-O-rhamnosylswertisin) were identified by LC-MS/MS whereas twenty-two compounds were identified by GC-MS but major proportions were n-hexadecanoic acid with 16.61% followed by linoleic acid, clionasterol, α-tocopherol, stigmast-7-en-3-ol, and α-amyrin. The GC-MS analysis of volatile oil obtained from leaves of A. pungens Kunth showed the presence of 12 compounds and the major compound was β-ionone (42.18%) (Ogunmoye et al., 2020). Other compounds identified were Hexahydrofarnesyl acetone (15.53%), Methyl palmitate (6.13%), 1-Octadecyne (4.72%), Undecane (3.73%), p-Metha-1,3,8-triene (3.65%), Isophytol (3.21%), δ-Cadinene (3.06%), 1,2-Dimethyl cyclooctene (3.05%), p-Cymene (2.96%), Phytol (2.67%) and Neophytadiene (2.50%).

The phytoconstituents—benzopyran, flavonoids, volatile oil, sterols, triterpenoid/saponins, phenolic compounds, ionone, anthraquinone, hydroxycinnamic acids, alkaloids, etc. have been scientifically reported from 9 species of Alternanthera. The chemical constituents (along with their structure) isolated from different species of the Alternanthera genus are shown in Table 1.

Referring to the data tabulated in Table 1 covering the isolated phytoconstituents from 9 species of Alternanthera genus, we have prepared an interactive mapping (Figure 2) to give some quick insight about it to the readers. Notably, it has also been observed that some of the phytocompounds like kaempferol, stigmasterol, quercetin, vitexin, ferulic acid, caffeic acid, etc have been isolated from various species of Alternanthera genus. This somehow lead us to suggest that these phytocompounds could serve as standardization of these markers could be helpful in identifying Alternanthera species, and avoid adulteration. Some of the compounds isolated from the species of Alternanthera genus are very common and usually been reported from multiple biological sources and well known for many pharmacological activities. For instance, kaempferol has been isolated from various other sources including Euonymus alatus (Thunb.) Siebold (Fang et al., 2008; Singla et al., 2021), Vachellia nilotica (L.) P.J.H.Hurter and Mabb.(Singh et al., 2008), etc, with multiple therapeutic potential, including but not limited to antiproliferative (Park et al., 2021), antiviral (Arabyan et al., 2021), hepatoprotective (Alshehri et al., 2021), antioxidant (Sharma et al., 2021), etc. Similarly, chlorogenic acid had been reported from multiple resources, including Cocos nucifera L. (Bankar et al., 2011), apple fruit (Hulme, 1953), Neolamarckia cadamba (Roxb.) Bosser (Kapil et al., 1995), etc with multiple therapeutic potential like neuroprotective (Hung et al., 2021), antihepatotoxic (Kapil et al., 1995), etc. Since species of Alternanthera genus containing other compounds also along with these common phytomolecules, there could be a possibility of synergistic potential and enhanced activity. Thus, we suggest the researchers to explore the therapeutic potential based on the common bioactive compounds.

FIGURE 2

FIGURE 2. Interaction analysis map to express association and relationship between phytochemical classifications, compounds, and biological sources.

Pharmacological Activities

Several scientific investigations were conducted to validate traditional claims of various species of Alternanthera. Uncharacterized/non-standardized crude extracts of various species of Alternanthera were used in most of these scientific pharmacological studies. Alternanthera species have been observed to display analgesic, anticancer, anti-inflammatory, antimicrobial, antioxidant, hepatoprotective, hypotensive, allelopathic, α-glucosidase inhibitory, anthelmintic, anti-allergic, antianxiety, sedative, antiapoptotic, antiarthritic, antiasthmatic, anticataract, anticonvulsant, antidepressant, antidiabetic, antidiarrhoeal, antifungal, antibacterial, anti-HBV, antiparkinsonian, antiprotozoal, antispasmodic, antiviral, gastrointestinal protective, immunomodulatory and wound healing activities. The plant species, extract/fraction/isolate, dose tested/route of administration, bioactive dose, positive control, negative control, In vivo/in vitro models, and mechanism of action have been summarized in Table 2.

TABLE 2

TABLE 2. Pharmacological activities of genus Alternanthera.

Referring to the data tabulated in Table 2, and interactive Figure 3, it is quite evident that the Alternanthera genus is having tremendous potential having polypharmacological effects. 35 different types of pharmacological effects were elicited by different species of Alternanthera genus. While the species like Alternanthera sessilis (L.) R.Br. ex DC., Alternanthera brasiliana (L.) Kuntze, and Alternanthera philoxeroides (Mart.) Griseb. were most widely explored, it opens up the opportunity for the researchers to explore other species of this genus.

FIGURE 3

FIGURE 3. Interactive analysis mapping between various species of Alternanthera genus and their elicited pharmacological properties.

Analgesic Activity

Pelisoli Formagio and the team had evaluated the aqueous extract from the aerial parts of Alternanthera brasiliana (L.) Kuntze for its analgesic potential. 90.35% reduction of acetic acid induced contractions were observed in mice, when treated with 25 mg/kg of the aqueous extract (Pelisoli Formagio et al., 2012). Coutinho and the team had performed the formalin test in mice for assessment of analgesic effect of ethanolic extract from the leaves of Alternanthera brasiliana (L.) Kuntze. At 100 mg/kg, ethanolic extract was capable of reducing the edematogenic process by 64.17% (Coutinho et al., 2017). Phytoconstituents like kaempferol (Parveen et al., 2007), quercetin (Anjaneyulu and Chopra, 2003), vitexin (Zhu et al., 2016), etc may be responsible for the analgesic potential of Alternanthera brasiliana (L.) Kuntze.

de Santana Aquino and the team had evaluated ethanolic extract as well as isolated compound, 2″-O-α-L-rhamnopyranosylvitexin from the aerial parts of Alternanthera littoralis P.Beauv. for analgesic potential. Results suggested that the ethanolic extract as well as 2″-O-α-L-rhamnopyranosylvitexin are capable of exerting significant analgesic effect, most probably through the TNF pathway (de Santana Aquino et al., 2015). Since kaempferol, quercetin, and vitexin were also been reported from Alternanthera littoralis P.Beauv. (Figure 2), so these compounds could also attribute in analgesic potential of the extract.

Khatun and the team had prepared the methanolic extract from the whole plant part of Alternanthera philoxeroides (Mart.) Griseb. and evaluated for its analgesic potential in the acetic acid induced mice. They found that 400 mg/kg dose of methanolic extract was capable of reducing constrictions by 44.8%. Phytoconstituents like kaempferol (Parveen et al., 2007), quercetin (Anjaneyulu and Chopra, 2003), vitexin (Zhu et al., 2016), caffeic acid (Gamaro et al., 2011), ursolic acid (Vasconcelos et al., 2006), etc may be responsible for the analgesic potential of Alternanthera philoxeroides (Mart.) Griseb.

Various research teams have independently assessed the analgesic potential of Alternanthera sessilis (L.) R.Br. ex DC.: Mondal and the team used ethanolic extract of the leaves (Mondal et al., 2014); Mohapatra and the team used hydroethanolic extract of leaves (Mohapatra et al., 2018); Hossain and the team used methanolic extract of aerial parts (Hossain et al., 2014); while Mohaimenul and the team used ethanolic extract of aerial parts (Mohaimenul et al., 2020). It is thus quite validated that aerial parts especially leaves of Alternanthera sessilis (L.) R.Br. ex DC. have the analgesic potential. Various mechanisms observed by those researchers for this activity. Some of them are like inhibition of interleukins like IL-4, IL-5, and IL-13, dopaminergic and serotonergic pathways, inhibition of lipoxygenase and cyclooxygenase, etc. Along with kaempferol, vitexin, and quercetin, compounds like stigmasterol (Walker et al., 2017) may also be responsible for such analgesic effect.

Anthelmintic Activity

Vennila and Nivetha had prepared various extracts from the leaves of Alternanthera sessilis (L.) R.Br. ex DC. and performed In vitro—Pheretima Posthuma method for assessment of anthelmintic activity. They observed that methanolic extract was the most potent and active at all the tested concentrations. The possible mechanism proposed by them was membrane lysis which subsequently led to paralysis or death of the worm (Vennila and Nivetha, 2015). On the other hand, Mondal and the team had assessed anthelmintic activity of ethanolic extract of the whole plant as well as the isolated ellagic acid by using In vitro—Adult motility test. They had also indicated the disruption of cell permeability, along with various other pathways and found ellagic acid a key responsible compound (Mondal et al., 2015). Other compounds that may be responsible for this pharmacological effects could be quercetin (Borges et al., 2020), β-sitosterol (Deepak et al., 2002), etc.

Antiallergic Activity

Rayees and the team checked the antiallergic activity of 95% ethanolic extract from aerial parts of Alternanthera sessilis (L.) R.Br. ex DC. Studies were conducted in rat basophilic leukemia (RBL-2H3) cells. They found that the treatment with ethanolic extract resulted in nuclear factor-KB (NF-kB) dependent inhibition of cytokines like IL-6, TNF-α, IL-13, and IL-4, along with the decrease in β-hexosaminidase release (Rayees et al., 2013). Compounds like β-sitosterol (Yuk et al., 2007; Mahajan and Mehta, 2011), kaempferol (Oh et al., 2013), quercetin (Mlcek et al., 2016), vitexin (Venturini et al., 2018), stigmasterol (Antwi et al., 2018), etc may be responsible for the antiallergic activity of Alternanthera sessilis (L.) R.Br. ex DC.

Antianxiety Property

Various research teams have independently assessed the antianxiety potential of Alternanthera brasiliana (L.) Kuntze: Pelisoli Formagio had used the aqueous extract of the leaves (Pelisoli Formagio et al., 2012); Oyemitan and the team had used the ethanolic extract of the leaves (Oyemitan et al., 2015); while Barua and the team had used the methanolic extract of the leaves (Barua et al., 2013). It is thus quite validated that the leaves of Alternanthera brasiliana (L.) Kuntze have the antianxiety potential. Various mechanisms observed by those researchers for this activity. Some of them are like activation of GABA receptor and 5-HT partial agonistic action. Phytomolecules like stigmasterol (Karim et al., 2021), kaempferol (Kaur et al., 2017), quercetin (Singh et al., 2013), p-coumaric acid (He Y. et al., 2021), etc may be responsible for this antianxiety property of Alternanthera brasiliana (L.) Kuntze.

Khamphukdee and the team had assessed ethanolic extract from the leaves of Alternanthera philoxeroides (Mart.) Griseb. for antianxiety potential by performing In vivo—Elevated plus-maze test, Light/Dark transition test, and Locomotor activity test in female mice. They observed that both the test doses i.e. 250 and 500 mg/kg/day of the extract was able to reduce the anxiety, most probably through the esterogenic pathway. Quercetin and kaempferol were detected in this plant also, so may be responsible for such antianxiety behavior.

Antiapoptotic Activity

Wu and the team had studied the antiapoptotic potential of ethanolic extract from the whole plant of Alternanthera bettzickiana (Regel) G.Nicholson. They found that ethanolic extract has strong tendency to reduce apoptosis which was modulated via multiple mechanisms including reduction of reactive oxygen species, inhibition of caspase-3 and caspase-9 activation, etc. They had reported quercetin as the major compound in that extract, and they found same mechanisms when evaluated quercetin for antiapoptotic potential.

Antiarthritic Activity

Manan and the team had studied antiarthritic potential of the ethanolic extract obtained from the aerial parts of Alternanthera bettzickiana (Regel) G.Nicholson using in silico, in vitro and in vivo methodologies. HPLC analysis indicated the presence of catechin, gallic acid, sinapic acid, chlorogenic acid, alpha-tocopherol, gamma-tocopherol, and quercetin. They have found that even the 250 mg/kg/day of the ethanolic extract was able to modulate the parameters suggesting the antiarthritic potential when compared with standard drug and disease control. In silico analysis suggested the strong interaction between the HPLC-analysed phytomolecules and cyclooxygenases (Manan et al., 2020).

Sunmathi and the team had studied the antiarthritic activity of ethanolic extracts obtained from the leaves of Alternanthera philoxeroides (Mart.) Griseb. and Alternanthera sessilis (L.) R.Br. ex DC. using in vitro methodologies. They found that 500 μg/ml of ethanolic extract of Alternanthera philoxeroides (Mart.) Griseb. and Alternanthera sessilis (L.) R.Br. ex DC. were able to stabilize the membrane by 64.92 and 75.43%, respectively. Phytomolecules like vitexin (Yang et al., 2019) and quercetin (Mamani-Matsuda et al., 2006) may be responsible for the antiarthritic activity of Alternanthera philoxeroides (Mart.) Griseb. and Alternanthera sessilis (L.) R.Br. ex DC.

Antiasthmatic Activity

Various research teams have independently assessed the antiasthmatic potential of Alternanthera sessilis (L.) R.Br. ex DC.: Fathima and the team had used ethanolic extract of leaves (Fathima et al., 2016) while Saqib and Janbaz had used 70% Ethanolic extract of the whole plant and its dichloromethane and aqueous fractions (Saqib and Janbaz, 2016). This validates the applicability of Alternanthera sessilis (L.) R.Br. ex DC. in the treatment management of asthma. Ethanolic extract obtained from the leaves was found to reduce the leucocyte count and significantly inhibited the histamine release (Fathima et al., 2016). 70% ethanolic extract of the whole plant was found to act via calcium channel blocking mechanism (Saqib and Janbaz, 2016). Phytomolecules like kaempferol (Gong et al., 2012), vitexin (Venturini et al., 2018), quercetin (Fortunato et al., 2012), stigmasterol (Antwi et al., 2017a), chlorogenic acid (Kim et al., 2010), etc. may be key components for the antiasthamatic activity of Alternanthera sessilis (L.) R.Br. ex DC.

Anticancer/Cytotoxic Property

Various research teams have independently assessed the anticancer property of Alternanthera bettzickiana (Regel) G.Nicholson: M Nagalingam and the team had used aqueous extract of the leaves (Nagalingam et al., 2018) while R Jothi Ramalingam and the team had used aqueous extract of leaves and silver nanoparticles and Ag-mesoporous MnO2 nanocomposite (Jothi Ramalingam et al., 2017). This validates the potential of leaves from Alternanthera bettzickiana (Regel) G.Nicholson and their nanoparticles in colon cancer and lung cancer. Apigenin analogues present in the Alternanthera bettzickiana (Regel) G.Nicholson may be responsible for the anticancer property (Madunić et al., 2018; Imran et al., 2020).

Similarly, various research teams have independently assessed the anticancer property of Alternanthera brasiliana (L.) Kuntze: Brochado and the team had used aqueous fraction of the ethanolic extract from the leaves. They had also isolated 6 bioactive compounds from this fraction viz. robinin, clovin, quercetin 3-O-robinobioside, kaempferol 3-O-robinobioside, kaempferol 3-O-rutinoside-7-O-a-L-rhamnopyranoside, and kaempferol 3-O-rutinoside (Brochado et al., 2003); Samudral and the team had used ethyl acetate extract obtained from the leaves (Samudrala et al., 2015). These pieces of evidence validates the anticancer potential of Alternanthera brasiliana (L.) Kuntze leaves. Brochado and the team found Kaempferol 3-O-robinobioside and kaempferol 3-O-rutinoside as the active phytomolecules (Brochado et al., 2003).

Independently several researches had also been conducted from various labs to assess the potential of Alternanthera philoxeroides (Mart.) Griseb. as anticancer agent: Zhang and the team had used the methanolic extract of the leaves and checked cytotoxicity against H9c2 cell lines. They found that even at 20 mg/ml, the methanolic extract was able to inhibit the doxorubicin induced cardiomyocyte apoptosis by more than 50%. They had also observed the presence of -carboline and quercetin (Zhang et al., 2018). Fang and the team had isolated 5 phytomolecules from the aerial parts of Alternanthera philoxeroides (Mart.) Griseb., and checked their inhibitory activity against Hela and L929 cell lines. While N-trans-feruloyl-3,5-dimethoxytyramine, alternanthin, N-trans-feruloyl-3-methyldopamine, and N-trans-feruloyl tyramine were found to have more than 50% inhibition at 30 μg/ml against Hela cell line, only Alternanthin B, and alternanthin were having more than 50% inhibition at 30 μg/ml against L929 cell line (Fang et al., 2007). Fang and the team had further isolated 4 more compounds from the aerial parts of Alternanthera philoxeroides (Mart.) Griseb. The triterpenoidal saponins, Philoxeroidesides A, B, C, and D were found to inhibit SK-N-SH cell line with an IC50 of 51, 118.69, 60.6, and 37.29 μg/ml, respectively, while inhibited HL60 cell line with an IC50 of 185.29, 185.57, 271.45, and 45.93 μg/ml, respectively. Philoxeroidesides D was found to be quite potential against both the cell lines (Fang J.-B. et al., 2009). In another study performed by Correa and the team where they had used ethanolic extracts obtained from the whole plant of Alternanthera philoxeroides (Mart.) Griseb.; Alternanthera hirtula (Mart.) R.E.Fr., and Alternanthera praelonga A.St.-Hil. They tested the ethanolic extracts against various human cancer cells lines including that from melanoma, breast, kidney, lung, prostate, ovary, colon, leukemia, along with non-cancer cell line from green monkey kidney. Out of all the cancer cell lines, these ethanolic extracts were being able to be found potent only against the leukemia cell line, K562 (Correa et al., 2016).

Several researchers have independently assessed the potential of Alternanthera sessilis (L.) R.Br. ex DC. for the management of cancer: Jain and the team had used the methanolic extract of leaves (Jain et al., 2016); Firdhouse and Lalitha had used silver nanoparticles of the aqueous extract (Firdhouse and Lalitha, 2013); Qian and the team had used gold nanoparticles of the aqueous extract of leaves (Qian et al., 2019); D Suganya and the team had used aqueous extract of leaves and stems (Suganya et al., 2019); Pathak and the team had used n-hexane and methanolic extracts of aerial parts (Pathak et al., 2020); Mohaimenul and the team had used ethanolic extract of aerial parts (Mohaimenul et al., 2020); Yap and the team had used ethanolic, 70% ethanolic, 80% methanolic, ethyl acetate, and aqueous extracts of the whole plant (Yap et al., 2019); Sathishkumar and the team had used silver nanoparticles of the aqueous extract of leaves (Sathishkumar et al., 2016); Arulselvan and the team had used ethanolic extract of aerial parts, stem, and leaves (Arulselvan et al., 2018); while Guerra and the team aqueous extract of aerial parts (Guerra et al., 2003). All these studies indicated the true potential of Alternanthera sessilis (L.) R.Br. ex DC. for the treatment and management of cancer, with leaving no doubt in it. Phytomolecules present in the Alternanthera sessilis (L.) R.Br. ex DC. like kaempferol (Imran et al., 2019), vitexin (Liu et al., 2019; Lee et al., 2020), quercetin (Rauf et al., 2018), stigmasterol (Ali et al., 2015), chlorogenic acid (Barahuie et al., 2017), campesterol (Bae et al., 2021), and β-sitosterol (Pradhan et al., 2016), etc. may be responsible for this anticancer property.

Anticataract Property

Kota and the team had checked the anticataract property of ethyl acetate extract obtained from the leaves of Alternanthera sessilis (L.) R.Br. ex DC. Cataract induced in eye lenses of the chicks were subjected for the treatment with 100, 200, and 400 mg of ethyl acetate extract, followed by analysis of lipid peroxidation and Na⁺- K⁺ ATPases. They found that 100 and 200 mg ethyl acetate treatment will lead to decrease in malondialdehyde and increase in the inorganic phosphorous content (Kota et al., 2017). Phytomolecules like quercetin (Lan et al., 2020), chlorogenic acid (Kim et al., 2011), and β-sitosterol (Haroon et al., 2020) may be responsible for this anticataract property of Alternanthera sessilis (L.) R.Br. ex DC.

Anticonvulsant Activity

Independently several researches had also been conducted from various labs to assess the potential of Alternanthera brasiliana (L.) Kuntze as anticonvulsant agent: Oyemitan and the team had used the ethanolic extract of leaves (Oyemitan et al., 2015); Schallenberger and the team had also used the ethanolic extract of leaves (Schallenberger et al., 2017); while Barua and the team had used the methanolic extract of leaves (Barua et al., 2013). This had validated the anticonvulsant potential of the leaves of Alternanthera brasiliana (L.) Kuntze. Various mechanisms elucidated by them are like modulation of GABAergic system, controlling the entry of calcium and sodium ions in the cells, and glycine regulation in spinal cord (Oyemitan et al., 2015). Phytomolecules like vitexin (de Oliveira et al., 2020), quercetin (Nassiri-Asl et al., 2014; Nieoczym et al., 2014), stigmasterol (Karim et al., 2021), chlorogenic acid (Aseervatham et al., 2016), and ferulic acid (Hassanzadeh et al., 2017) may be responsible for the antiepileptic effect of Alternanthera brasiliana (L.) Kuntze.

Antidepressant Activity

Khamphukdee and the team had assessed the antidepressant effect of the ethanolic extract obtained from the leaves of Alternanthera philoxeroides (Mart.) Griseb. They found that the extract was having significant antidepressant effect modulated through the estrogenic pathway (Khamphukdee et al., 2018). Phytomolecules like quercetin (Anjaneyulu and Chopra, 2003), vitexin (Can et al., 2013), β-sitosterol (Zhao et al., 2016), p-coumaric acid (Lee et al., 2018), caffeic acid (Monteiro et al., 2020), ursolic acid (Machado et al., 2012; Singla et al., 2017), and malic acid (Gómez-Moreno et al., 2013) may be responsible for the antidepressant activity of Alternanthera philoxeroides (Mart.) Griseb.

Gupta and K. Singh had evaluated the antidepressant activity of methanolic extract obtained from the leaves of Alternanthera sessilis (L.) R.Br. ex DC. They had observed that the antidepressant effect of the methanolic extract was acting via interaction with adrenergic, dopaminergic serotonergic, and GABAergic system (Gupta and Singh, 2014). Phytomolecules like quercetin, vitexin, and p-coumaric acid had also been reported from Alternanthera sessilis (L.) R.Br. ex DC., along with other antidepressant agents like kaempferol (Park et al., 2010b), ferulic acid (Chen et al., 2014) and chlorogenic acid (Park et al., 2010a). These phytomolecules may be responsible for the antidepressant activity of Alternanthera sessilis (L.) R.Br. ex DC.

Antidiabetic Activity

Reza and the team had assessed the antidiabetic potential of 80% ethanolic extracts obtained from the stem and leaves of Alternanthera brasiliana (L.) Kuntze. They found that the ethanolic extracts were being able to significantly modulate the biochemical parameters like blood glucose, lipid peroxidation, and free radicals in the alloxan-induced diabetic Swiss albino mice (Reza et al., 2019). Phytomolecules like kaempferol (Ibitoye et al., 2018), quercetin (Vessal et al., 2003), stigmasterol (Wang et al., 2017; Singla and Shen, 2020), p-coumaric acid (Amalan et al., 2016), ferulic acid (Narasimhan et al., 2015), and chlorogenic acid (Ong et al., 2013) may be responsible for the antidiabetic potential of Alternanthera brasiliana (L.) Kuntze.

Khatun and the team as well as Bhattacherjee and the team had independently assessed the antidiabetic activity of Alternanthera philoxeroides (Mart.) Griseb. Various important mechanisms had been observed by them including regeneration of the β-cells of the pancreas, alpha-glucosidase inhibition, as well as the inhibition of the glucose absorption from the gut wall (Khatun et al., 2012; Bhattacherjee et al., 2014). Compounds like quercetin and p-coumaric acid had been reported from Alternanthera philoxeroides (Mart.) Griseb., and may be responsible for such antidiabetic effect.

Mourya and the team had used aqueous and ethanolic extracts obtained from the whole plant of Alternanthera pungens Kunth for the assessment of antidiabetic potential. Dose dependent antidiabetic activity was observed by them when studied in alloxan-induced diabetic Wistar rats. Phytocompounds like camphene (Hachlafi et al., 2021), camphor (Drikvandi et al., 2020), geraniol (Babukumar et al., 2017), and limonene (Murali and Saravanan, 2012) may be responsible for such antidiabetic property of Alternanthera pungens Kunth.

Independently several researches had also been conducted from various labs to assess the potential of Alternanthera sessilis (L.) R.Br. ex DC. as antidiabetic agent: Kumar and the team had used aqueous and ethanolic extracts of aerial parts (Kumar S. M. et al., 2011); Tan and Kim had used hexane, ethyl acetate, and aqueous fractions of aerial parts (Tan and Kim, 2013); Hossain and the team had used methanolic extract of aerial parts (Hossain et al., 2014); Sundar and the team had used petroleum ether extract of leaves (Sundar et al., 2019); Das and the team had used 95% ethanolic extract of the whole plant (Das et al., 2015); Rao and the team had used ethanolic extract of the whole plant (Rao et al., 2011); Manalo and the team had used n-hexane, ethyl acetate, and water fractions of the methanolic extract of leaves (Manalo et al., 2020); Mohaimenul and the team had used ethanolic extract of aerial parts (Mohaimenul et al., 2020); Tiwari and the team had used the juice (Tiwari et al., 2013); Chai and the team had used hexane, chloroform, ethyl acetate, butanol, and aqueous fractions of methanolic extracts of leaves and callus (Chai et al., 2016). Plenty of evidences obtained from the above researches leaved no doubt in that fact that Alternanthera sessilis (L.) R.Br. ex DC. possesses antidiabetic properties. Various mechanisms demonstrated by different preparations from Alternanthera sessilis (L.) R.Br. ex DC., including but not limited to modulation of insulin sensitivity, improvement in pancreatic insulin secretion, reduction in blood glucose level, inhibition of α-glucosidase enzyme, etc. Phytomolecules like kaempferol (Ibitoye et al., 2018), quercetin (Vessal et al., 2003), stigmasterol (Wang et al., 2017; Singla and Shen, 2020), 4-hydroxybenzoic acid (Peungvicha et al., 1998), β-sitosterol (Ponnulakshmi et al., 2019), ellagic acid (Fatima et al., 2015), ferulic acid (Narasimhan et al., 2015), and chlorogenic acid (Ong et al., 2013) may be responsible for the antidiabetic potential of Alternanthera sessilis (L.) R.Br. ex DC.

Antidiarrheal Activity

Zavala and the team had evaluated the antidiarrheal property of hexane, chloroform, methanolic, and aqueous extracts obtained from the whole plant of Alternanthera sessilis (L.) R.Br. ex DC. They had observed that out of all extracts, methanolic and aqueous extracts had shown significant inhibition of castor oil-induced diarrhea. Methanolic extract was further found to inhibit normal defecation in mice also. Peristaltic movement was also modulated by the methanolic extract (Zavala et al., 1998). Phytomolecules like quercetin (Lozoya et al., 1994; Song et al., 2011; Shi et al., 2020), β-sitosterol (Ding et al., 2018), ellagic acid (Chen et al., 2020), ferulic acid (Hu et al., 2021), and chlorogenic acid (Zhang et al., 2017; Chen et al., 2018) may be responsible for the antidiarrheal property of Alternanthera sessilis (L.) R.Br. ex DC.

Antigout Activity

Chong and Loh had assessed the antigout potential of methanolic extract obtained from the aerial parts of Alternanthera sessilis (L.) R.Br. ex DC. Methanolic extract was able to inhibit xanthine oxidase enzyme with an IC50 of 557.77 μg/ml (Chong and Loh, 2020). Phytomolecules like kaempferol (Wang et al., 2015d), quercetin (Bindoli et al., 1985), stigmasterol (Chiang and Chen, 2008), ellagic acid (Sun et al., 2021), ferulic acid (Nile et al., 2016), and chlorogenic acid (Wang et al., 2009) may be responsible for the antigout potential of Alternanthera sessilis (L.) R.Br. ex DC.

Anti-Hepatitis B Virus Activity

Li and the team had isolated C-boivinopyranosyl flavones from Alternanthera philoxeroides (Mart.) Griseb. and found that luteolin-6-C-β-d-boivinopyranosyl-3′-O-β-d-glucopyranoside, chrysoeriol-6-C-β-d-Boivinopyranosyl-4′-O-β-d-glucopyranoside, and luteolin-6-C-β-d-boivinopyranosyl-4′-O-β-d-glucopyranoside were strongly inhibiting the viral antigen, HBsAg in HBV-infected HepG2.2.15 with an IC50 of 28.65, 22.20, and 31.54 µM, respectively (Li et al., 2016).

Antihypertensive Activity

Saqib and Janbaz had evaluated the antihypertensive effect of 70% Ethanolic extract of the whole plant and its dichloromethane and aqueous fractions from Alternanthera sessilis (L.) R.Br. ex DC. The in vivo studies suggested that the ethanolic extract was capable to reducing both the systolic and the diastolic pressure. Phytomolecules like kaempferol (Ahmad et al., 1993; Binang and Takuwa, 2021), quercetin (Perez-Vizcaino et al., 2009; Binang and Takuwa, 2021), vitexin (Xue et al., 2020), β-sitosterol (Olaiya et al., 2014), ellagic acid (Berkban et al., 2015), ferulic acid (Li et al., 2020), and chlorogenic acid (Zhao et al., 2011) may be responsible for the antihypertensive potential of Alternanthera sessilis (L.) R.Br. ex DC.

Anti-Inflammatory Activity

Pelisoli Formagio and the team had performed the in vivo studies to assess the anti-inflammatory activity of the aqueous extract obtained from the leaves of Alternanthera brasiliana (L.) Kuntze while P Shivashankar and the team had used the methanolic extract obtained from the leaves. Pelisoli Formagio and the team had observed the significant decrease in the polymorphonuclear cells as well as increase in the mononuclear cells in rat’s exudate after treated with the aqueous extract, while P Shivashankar and the team found the reduction in the colon weight in acetic acid-induced colitis model of adult Wistar albino rats after treatment with the methanolic extract (Pelisoli Formagio et al., 2012; P et al., 2016). Phytomolecules like kaempferol (Devi et al., 2015), quercetin (Lesjak et al., 2018), stigmasterol (Morgan et al., 2021), p-coumaric acid (Pragasam et al., 2012), ferulic acid (Ozaki, 1992), and chlorogenic acid (Hwang et al., 2013) may be responsible for the anti-inflammatory potential of Alternanthera brasiliana (L.) Kuntze.

de Santana Aquino and the team had evaluated anti-inflammatory activity of ethanolic extract of aerial parts and the isolated compound, 2″-O-α-L-rhamnopyranosylvitexin from Alternanthera littoralis P.Beauv. They found that the ethanolic extract was able to reduce the paw edema as well as capable to reducing leukocyte migration. In addition to these, the isolated compound was also able to reduce protein leakage into the pleural cavity (de Santana Aquino et al., 2015). Other phytomolecules that could be responsible for the anti-inflammatory activity of the ethanolic extract will be kaempferol, quercetin, stigmasterol, etc.

Sunmathi and the team had evaluated anti-inflammatory activity of ethanolic extract obtained from the leaves of Alternanthera philoxeroides (Mart.) Griseb. Dose dependent membrane stabilization was observed. Phytomolecules like quercetin (Lesjak et al., 2018), vitexin (Rosa et al., 2016), β-sitosterol (Loizou et al., 2010), p-coumaric acid (Pragasam et al., 2012), caffeic acid (da Cunha et al., 2009), ursolic acid (Baricevic et al., 2001), and malic acid (Obertreis et al., 1996) may be responsible for the anti-inflammatory activity of Alternanthera philoxeroides (Mart.) Griseb.

Franck and the team had evaluated the anti-inflammatory activity of aqueous extract obtained from the leaves of Alternanthera pungens Kunth. They had observed the decreased level of histamine release, serotonin and kinin, prostaglandin, proteases, lysosomes, and protein C-reactive. Phytomolecules like α-pinene (Kim et al., 2015), myrcene (Rufino et al., 2015), limonene (Rufino et al., 2015), choline (Rowley et al., 2010), rhein (Gao et al., 2014), linalool (Peana et al., 2002), geraniol (Ye et al., 2019), and camphor (Ehrnhöfer-Ressler et al., 2013) which were reported earlier in Alternanthera pungens Kunth., may be responsible for this anti-inflammatory effect.

Independently several researches had also been conducted from various labs to assess the potential of Alternanthera sessilis (L.) R.Br. ex DC. as anti-inflammatory agent: Sunmathi and the team had used ethanolic extract obtained from the leaves (Sunmathi et al., 2016); Muniandy and the team had used 90% ethanolic extract of stems (Muniandy et al., 2018a); Sundar and the team had used petroleum ether and methanolic extracts of leaves (Sundar et al., 2019); Kassuya and the team had used Ethanolic extract of whole plant (EEAT) as well as the isolated molecule, 2″-O-β-D-glucopyranosyl-vitexin (Kassuya et al., 2021); Biella and the team had used aqueous extract of the whole plant (Biella et al., 2008). Plenty of evidences obtained from the above researches leaved no doubt in that fact that Alternanthera sessilis (L.) R.Br. ex DC. possesses anti-inflammatory properties. Various mechanisms demonstrated by different preparations from Alternanthera sessilis (L.) R.Br. ex DC., including but not limited to cyclooxygenase -1 and -2 inhibition (Biella et al., 2008), modulating NF- κB pathway (Muniandy et al., 2018a), leukocyte migration (Kassuya et al., 2021), etc. Phytomolecules like kaempferol (Devi et al., 2015; Pizzo et al., 2018), quercetin (Lesjak et al., 2018), vitexin (Rosa et al., 2016), stigmasterol (Morgan et al., 2021), β-sitosterol (Loizou et al., 2010), 4-hydroxybenzoic acid (Winter et al., 2017), ellagic acid (Corbett et al., 2010), ferulic acid (Ozaki, 1992), campesterol (Moreno-Anzúrez et al., 2017), spinasterol (Jeong et al., 2010), β-carotene (Uteshev et al., 2000), p-coumaric acid (Pragasam et al., 2012), ricinoleic acid (Vieira et al., 2001), and chlorogenic acid (Hwang et al., 2013) may be responsible for the anti-inflammatory potential of Alternanthera sessilis (L.) R.Br. ex DC.

Antimicrobial Activity

Independently, several research teams had evaluated the antimicrobial effects of the leaves of Alternanthera bettzickiana (Regel) G.Nicholson: Vidhya and the team had used hexane, chloroform, ethyl acetate, methanolic, and aqueous extracts of leaves (Vidhya et al., 2015); R, Jothi Ramalingam and the team had used aqueous extract of leaves and silver nanoparticles and Ag-mesoporous MnO2 nanocomposite (Jothi Ramalingam et al., 2017); Nagalingam and the team had used the aqueous extract obtained from leaves (Au-NP) (Nagalingam et al., 2018). These research were focused on leaves and somehow validated the antimicrobial property of it. Various mechanisms elucidated were like cell wall lysis, protein synthesis inhibition, and topoisomerase inhibition, etc (Vidhya et al., 2015; Jothi Ramalingam et al., 2017; Nagalingam et al., 2018). Phytocompounds like apigenin analogs (Koo, 2003; Thirukumaran et al., 2019) may be responsible for this antimicrobial property of Alternanthera bettzickiana (Regel) G.Nicholson.

Coutinho and the team had evaluated the antimicrobial property of ethanolic extract obtained from the leaves of Alternanthera brasiliana (L.) Kuntze. They had observed that though the ethanolic extract as such was having insignificant potential, but it elicited significant synergetic potential when combined with gentamycin and tested against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa (Coutinho et al., 2017). Johann and the team had also performed the antimicrobial experiments on the ethanolic extract obtained from the aerial parts of Alternanthera brasiliana (L.) Kuntze, and they had also observed that the extract was inactive against various murine macrophages and fungal strains (Johann et al., 2010). Other research team like that of Akachukwu and Uchegbu had also reported mild activity of the ethanolic extract obtained from its leaves (Akachukwu and Uchegbu, 2016) while Kumar and the team noticed significant activity elicited by the silver nanoparticles obtained from the leaves aqueous extract (Kumar et al., 2014).

Canales-Martínez and the team had evaluated the antimicrobial effect of the hexane, chloroform, methanolic, acetone, and ethyl acetate extracts obtained from the aerial parts of Alternanthera caracasana Kunth and also isolated a bioactive compound, 7-methoxycoumarin. They observed that the ethyl acetate extract as well as 7-methoxycoumarin were active against various Gram-positive and Gram-negative bacterial strains, but inactive against Candida albicans (Canales-Martínez et al., 2008). Phytochemical profiling of Alternanthera caracasana Kunth is still not done, leaving a scope for the researchers.

Gasparetto and the team had used crude hexane and ethanolic extract obtained from the leaves of Alternanthera littoralis P.Beauv., and assessed them for their antimicrobial potential. They noticed that the antifungal activity was exhibited by the crude extracts only when combined with photo-irradiation by a diode laser (Gasparetto et al., 2010). Phytocompounds like kaempferol (del Valle et al., 2016), stigmasterol (Alawode et al., 2021), hydroxytyrosol (Bisignano et al., 1999), quercetin (Gatto et al., 2002), vitexin (Das et al., 2016), and uridine (Wiegmann et al., 2016) which were reported earlier from Alternanthera littoralis P.Beauv., may be responsible for such antimicrobial effects.

Feka and the team had studied the antimicrobial property of the aqueous and methanolic extracts obtained from the whole plant of Alternanthera nodiflora R.Br. They found that the methanolic extract was having significant antimicrobial activity against bacterial and yeast strains, but inactive against mould test strain (Feka et al., 2014). Phytochemical profiling of Alternanthera nodiflora R.Br. is still not done, leaving a scope for the researchers.

Independently several research teams had evaluated the antimicrobial potential of Alternanthera philoxeroides (Mart.) Griseb.: Bhattacherjee and the team had used methanol-soluble fraction obtained from the leaves (Bhattacherjee et al., 2014); Rawani and the team had used aqueous and chloroform: methanol (1:1) extracts of leaves (Rawani et al., 2011); Pulipati and the team had used ethanolic extract obtained from the leaves (Pulipati et al., 2016); Akbar and the team had used methanolic extract of leaves, stem and roots as well as their n-hexane, chloroform and ethyl acetate fractions (Akbar et al., 2021); while Pulipati and Babu had used the methanolic extract of leaves (Pulipati and Babu, 2020). These independent researches left no doubt and validated the antimicrobial feature of Alternanthera philoxeroides (Mart.) Griseb. They had reported multiple mechanisms of actions like bacterial cell wall lysis and protein synthesis inhibition (Bhattacherjee et al., 2014; Pulipati et al., 2016; Pulipati and Babu, 2020). Phytomolecules like quercetin (Gatto et al., 2002), vitexin (Das et al., 2016), β-sitosterol (Ododo et al., 2016), stigmasterol (Alawode et al., 2021), p-coumaric acid (Boz, 2015), caffeic acid (Lima et al., 2016), luteolin analogs (Chiruvella et al., 2007; Qian et al., 2020), chrysoeriol analogs (Jang et al., 2020), malic acid (Raybaudi-Massilia et al., 2009), β-carboline (Arshad et al., 2008; Suzuki et al., 2018), ursolic acid (Collins and Charles, 1987), oleanolic acid (Horiuchi et al., 2007), azelaic acid (Leeming et al., 1986), phytol (Pejin et al., 2014), and rubiadin (Marioni et al., 2016) which were earlier reported from Alternanthera philoxeroides (Mart.) Griseb., may be responsible for this antimicrobial property.

Jakhar and Dahiya had studied the aqueous, acetone, ethanolic, and petroleum ether extracts obtained from the aerial parts of Alternanthera pungens Kunth for assessment of antimicrobial effect against various bacterial and fungal strains. They found that all the extracts were having potential as antibacterial, but the antifungal property was exhibited by only acetone and aqueous extracts. Noticed mechanisms were inhibition of DNA replication as well as blocking of cellular respiration. Phytochemicals like choline (Siopa et al., 2016), rhein (Joung et al., 2012), limonene (Vuuren and Viljoen, 2007), α-curcumene (Santos da Silva et al., 2015), geraniol (Lira et al., 2020), linalool (Park S.-N. et al., 2012), camphor (Masry et al., 2021), myrcene (Chaves-Quirós et al., 2020), and α-pinene (Dhar et al., 2014; Cloeckaert et al., 2015) which were earlier reported from Alternanthera pungens Kunth, may be responsible for such antimicrobial action.

Plenty of independent researches have been extracted from the literature, covering evaluation of antimicrobial activity of Alternanthera sessilis (L.) R.Br. ex DC.: Osuna and the team had used hexane and methanolic extracts obtained from the aerial parts (Osuna et al., 2008); Jalalpure and the team had used petroleum ether (40–60°C), chloroform, acetone, methanolic, and aqueous extracts of leaves (Jalalpure et al., 2008); Monroy and Limsiaco had used aqueous, ethanolic, and acetone extracts obtained from leaves (Monroy and Limsiaco, 2016); Niraimathi and the team had used silver nanoparticles of aqueous extract of leaves (Niraimathi et al., 2013); Rajamurugan and the team had used ethanolic extract obtained from the leaves (Rajamurugan et al., 2013); D Suganya and the team had used aqueous extract of leaves and stems (Suganya et al., 2019); Kota and the team had used petroleum ether, ethyl acetate, chloroform, and methanolic extract obtained from the leaves (Kota et al., 2017); Sundar and the team had used petroleum ether and methanolic extracts of leaves (Sundar et al., 2019); while Salvador and the team had used hexane and ethanolic extracts obtained from the adult plants (Salvador et al., 2009). These studies clearly concluded that Alternanthera sessilis (L.) R.Br. ex DC. possesses antimicrobial properties. Several mechanisms elucidated by them are like cell membrane lysis, prevention of protein synthesis, blocking cellular respiration, inhibition of DNA replication, deprivation of iron for microbial growth, etc (Osuna et al., 2008; Salvador et al., 2009; Rajamurugan et al., 2013; Monroy and Limsiaco, 2016; Kota et al., 2017; Suganya et al., 2019). Phytomolecules like Vitexin (Das et al., 2016), Kaempferol (del Valle et al., 2016), Quercetin (Gatto et al., 2002), Kaempferol-7- O-glucoside (Singh et al., 2011), Stigmasterol (Alawode et al., 2021), β-Sitosterol (Ododo et al., 2016), Ellagic acid (Abuelsaad et al., 2013; De et al., 2018), Ferulic acid (Shi et al., 2016), p-Coumaric acid (Boz, 2015), 4-Hydroxybenzoic acid (Cho J.-Y. et al., 2014), 2,5-Dihydroxybenzoic acid (Kim et al., 2007), Chlorogenic acid (Li et al., 2013; Kabir et al., 2014), Ionone (Mikhlin et al., 1983), β-Carotene (Hayashi et al., 2012), and Ricinoleic acid (Novak et al., 1961) which were earlier reported from Alternanthera sessilis (L.) R.Br. ex DC. may be responsible for its antimicrobial property.

Antioxidant Activity

Petrus and the team had evaluated the antioxidant activity of the 80% aqueous methanolic extract obtained from the flowers of Alternanthera bettzickiana (Regel) G.Nicholson. They had observed that the extract possessed radical scavenging and ferrous ion chelating properties (Petrus A. et al., 2014). On the other hand, Vidhya and the team had evaluated the antioxidant activity of the hexane, chloroform, ethyl acetate, methanolic, and aqueous extracts obtained from the leaves Alternanthera bettzickiana (Regel) G.Nicholson. They observed that out of all, methanolic extract was exhibiting stronger radical scavenging activity (Vidhya et al., 2015). Phytomolecules like apigenin analogs (Prince Vijeya Singh et al., 2004) which were earlier reported from Alternanthera bettzickiana (Regel) G.Nicholson, may be responsible for this antioxidant potential.

Independently, several research teams had investigated the antioxidant potential of Alternanthera brasiliana (L.) Kuntze: Reza and the team had used 80% ethanolic extract of stem and leaves (Reza et al., 2019); Enechi and the team had used ethanolic extract of leaves (Enechi et al., 2013); Chandran R had used methanolic extract of leaves (Chandran, 2017); Attaugwu and Uvere had used ethanolic extract of leaves (Attaugwu and Uvere, 2017); Pereira and the team had used ethanolic extract and its dichloromethane, ethyl acetate, n-butanolic fractions of leaves (Pereira et al., 2013); Araujo and the team had used ethanolic extract of aerial parts and its hexane, chloroform, and ethyl acetate fractions (Araujo et al., 2014); while Akachukwu and Uchegbu had used ethanolic extract of leaves (Akachukwu and Uchegbu, 2016). These pieces of evidence increase the credibility of Alternanthera brasiliana (L.) Kuntze as antioxidant. Phytoconstituents like Ligustroflavone (Kang et al., 2021), Vitexin (An et al., 2012), Kaempferol (Park et al., 2006), Quercetin (Zhang et al., 2011), Tricin (Duarte-Almeida et al., 2007), Quercetin 3-β-D-glucoside (Niranjan Panat et al., 2015), Isorhamnetin-3-O-robinobioside (Boubaker et al., 2012), Stigmasterol (Liang et al., 2020), β-Sitosterol (Gupta et al., 2011), Ferulic acid (Graf, 1992), p-Coumaric acid (Kiliç and Yeşiloğlu, 2013), 4-Hydroxybenzoic acid (Velika and Kron, 2012), 2,5-Dihydroxybenzoic acid (Calderón Guzmán et al., 2007), Chlorogenic acid (Sato et al., 2011), Dopamine-betaxanthin (Cai et al., 2003), and 3-Methoxytyramine-betaxanthin (Cai et al., 2003) which were earlier reported from Alternanthera brasiliana (L.) Kuntze, may be responsible for its antioxidant property.

Patil and Kore had evaluated the antioxidant property of methanolic extracts obtained from different parts viz. leaves, stem, and roots of Alternanthera ficoidea (L.) P.Beauv. They had observed that out of all, the methanolic extract from the roots was having most potent antioxidant activity (Patil and Kore, 2019). To the best of our knowledge, the phytochemial characterization of Alternanthera ficoidea (L.) P.Beauv. was not yet done, leaving an ample scope for the researchers.

Koolen and the team had isolated seven phytoconstituents from the aerial sections of Alternanthera littoralis P.Beauv. and evaluated them for the antioxidant potential using In vitro—ORAC assay. They had observed that out of all compounds, Alternamide B was the most significant one as antioxidant. Researchers had further suggested the catechol scaffold as a pharmacophore for this activity (Koolen et al., 2017).

Two independent research teams had evaluated the antioxidant potential of Alternanthera paronychioides A.St.-Hil.: Wu and the team had used methanolic, ethanolic, and aqueous extracts of the whole plant (Wu et al., 2013) while Tukun and the team had used aqueous extract obtained from the leaves (Tukun et al., 2014). These preliminary studies signifies the role of Alternanthera paronychioides A.St.-Hil. as antioxidant. To the best of our knowledge, the phytochemial characterization of Alternanthera paronychioides A.St.-Hil. was not yet done, leaving an ample scope for the researchers.

Bhattacherjee and the team had evaluated the antioxidant activity of methanol soluble fraction obtained from the leaves of Alternanthera philoxeroides (Mart.) Griseb. (Bhattacherjee et al., 2014). while Correa and the team had used ethanolic extracts of the whole plant (Correa et al., 2016). These preliminary studies suggested that the Alternanthera philoxeroides (Mart.) Griseb. is worthy of further investigation as antioxidant. Phytomolecules like Luteolin and luteolin analogs (Romanova et al., 2001), Chrysoeriol analogs (Mishra et al., 2003), Vitexin (An et al., 2012), Quercetin (Zhang et al., 2011), β-Sitosterol (Gupta et al., 2011), Δ5-Stigmasterol (Liang et al., 2020), Ursolic acid (Bobé et al., 2012; do Nascimento et al., 2014), Oleanolic acid and Oleanolic acid analogs (Wang et al., 2010), Calenduloside E (Tang et al., 2019), Caffeic acid (Gulcin, 2006), Quinic acid (Pero et al., 2009), p-Coumaric acid (Kiliç and Yeşiloğlu, 2013), Rubiadin (Tripathi et al., 1997), β-Carboline (Moura et al., 2007), Malic acid (Jin et al., 2016), Azelaic acid (Muthulakshmi and Saravanan, 2013), Cycloeucalenol (Wang W. et al., 2015), Phytol (Santos et al., 2013), and Pheophytin A (Endo et al., 1985) which were previously been reported from Alternanthera philoxeroides (Mart.) Griseb., may be responsible for this antioxidant property.

Several research teams have independently assessed the antioxidant potential of Alternanthera pungens Kunth: Mourya and the team had used ethanolic and aqueous extracts obtained from the leaves (Mourya et al., 2019); Franck and the team had used aqueous extract of leaves (Franck et al., 2016); while Jakhar and Dahiya had used aqueous, acetone, ethanolic, and petroleum ether extracts of aerial parts (Jakhar and Dahiya, 2017). These studies validated the antioxidant potential of Alternanthera pungens Kunth. Various phytochemicals like Limonene (Roberto et al., 2009), Geraniol (Aytac et al., 2016), Linalool (Duarte et al., 2016), Camphor (Drikvandi et al., 2020), Myrcene (Khalili et al., 2020), Camphene (Tiwari and Kakkar, 2009), and α-pinene (Aydin et al., 2013) which were reported earlier from Alternanthera pungens Kunth, may be responsible for its antioxidant action.

While going through literature, we have found enough pieces of evidences reporting and validating the antioxidant property of Alternanthera sessilis (L.) R.Br. ex DC.: Borah and the team had used 90% methanolic, 70% acetone, 80% ethanolic extracts of leaves and stems (Borah et al., 2011); Chai and the team had used hexane, chloroform, ethyl acetate, butanolic, and aqueous fractions of leaves and callus methanol extracts (Chai et al., 2016); Sharma and the team 30% hydroethanolic extract of the whole plant (Sharma et al., 2013); Khan and the team had used separate Methanolic and hexane extracts of leaves and stems (Khan et al., 2018); Azizah and the team had used ethanolic and aqueous extracts of aerial parts (Azizah et al., 2015); Muniandy and the team had used 90% hydroethanolic extract of stem (Muniandy et al., 2018b); Othman and the team had used ethanolic and aqueous extracts of aerial parts (Othman et al., 2016); Tiwari and the team had used juice (Tiwari et al., 2013); Rajamurugan and the team had used ethanolic extract of leaves (Rajamurugan et al., 2013); Jain and the team had used methanolic extract of leaves (Jain et al., 2016); Suganya and the team had used aqueous extract of leaves and stems (Suganya et al., 2019); Mohd Hazli and the team had used hexane, ethyl acetate, ethanolic, and aqueous extracts of leaves and stem (Mohd Hazli et al., 2019); Niraimathi and the team had used silver nanoparticles from aqueous extract of leaves (Niraimathi et al., 2013); Yap and the team had used 100% ethanolic, 70% ethanolic, 80% methanolic, ethyl acetate, and aqueous extracts of the whole plant (Yap et al., 2019); Kota and the team had used petroleum ether, ethyl acetate, chloroform, and methanolic extract of leaves (Kota et al., 2017); Sundar and the team had used petroleum ether and methanolic extracts of leaves (Sundar et al., 2019); Pathak and the team had used n-hexane and methanolic extracts of aerial parts (Pathak et al., 2020); Khan and the team had used the volatile oil of leaves and flowers (Khan et al., 2016); while Salvador and the team had used ethanolic extract and its four fractions; Acacetin 8-c-[α-L-rhamnopyranoyl-(1→2)-β-D-glucopyranoside]; 2″-O-α-L-rhamnopyranosyl-vitexin; 2″-O-β-D-glucopyranosyl vitexin and Vitexin (Salvador et al., 2006). Results from these researches left no doubt in the credibility and applicability of Alternanthera sessilis (L.) R.Br. ex DC. in reducing oxidative stress. Phytomolecules like Vitexin and vitexin analogs (An et al., 2012), Kaempferol and kaempferol analogs (Park et al., 2006), Quercetin and quercetin analogs (Zhang et al., 2011), Acacetin analogs (Li et al., 2019), Isorhamnetin-3-O-robinobioside (Boubaker et al., 2012), Stigmasterol (Liang et al., 2020), Campesterol (Yoshida and Niki, 2003), β-Sitosterol (Gupta et al., 2011), Spinasterol (Adebiyi et al., 2018), Ellagic acid (Priyadarsini et al., 2002), Ferulic acid (Graf, 1992), p-Coumaric acid (Kiliç and Yeşiloğlu, 2013), 4-Hydroxybenzoic acid (Velika and Kron, 2012), 2,5-Dihydroxybenzoic acid (Calderón Guzmán et al., 2007), Chlorogenic acid (Sato et al., 2011), Ionone (Liu et al., 2009), β-Carotene (Paiva and Russell, 1999), Ricinoleic acid (Park et al., 2020), Dopamine-betaxanthin (Cai et al., 2003), and 3-Methoxytyramine-betaxanthin (Cai et al., 2003) which were earlier been reported from Alternanthera sessilis (L.) R.Br. ex DC., may be responsible for its antioxidant action.

Antiparkinsonism/Antidementia Property

Khamphukdee and the team had evaluated the antidementia activity of the ethanolic extract obtained from the whole plant of Alternanthera philoxeroides (Mart.) Griseb. They had noticed various mechanisms behind it like inhibition of lipid peroxidation in the whole brain, downregulation of neuroinflammatory cytokines (IL-1β, IL-6, and TNF-α), etc (Khamphukdee et al., 2021). Phytomolecules like Luteolin and luteolin analogs (Delgado et al., 2021), Vitexin (Malar et al., 2020; Zhang et al., 2021), Quercetin (Yao et al., 2010), Torosaflavone E (Khamphukdee et al., 2021), Demethyl torosaflavone D (Khamphukdee et al., 2021), β-Sitosterol (Kim et al., 2008), Stigmasterol (Park S. J. et al., 2012; Pratiwi et al., 2021), Ursolic acid (Habtemariam, 2019), Oleanolic acid and oleanolic acid analogs (Lin et al., 2021), Caffeic acid (Khan et al., 2013; Deshmukh et al., 2016), Quinic acid (Liu et al., 2020), p-Coumaric acid (Kim H.-B. et al., 2017), β-Carboline (Zhao et al., 2013; Li et al., 2018), Malic acid (Tian et al., 2021), Blumenol A (Emir et al., 2019), Phytol (Sathya et al., 2020), and Pheophytin A (Park et al., 2014) which were earlier reported from Alternanthera philoxeroides (Mart.) Griseb., may be responsible for this antidementia property.

Ittiyavirah and Hameed had evaluated the antiparkinsonian activity of silver nanoparticles and ethanolic extract obtained from the whole plant of Alternanthera sessilis (L.) R.Br. ex DC. They had observed that the silver nanoparticles as well as the ethanolic extract were able to impart neuroprotection with decrease in catalepsy as well as in muscle rigidity, along with locomotion improvement (Ittiyavirah and Hameed, 2015). Phytomolecules like Vitexin and vitexin analogs (Hu et al., 2018), Kaempferol and kaempferol analogs (Filomeni et al., 2012), Quercetin-3-methyl ether (Kim et al., 2009), Quercetin (Lv et al., 2012), Acacetin analogs (Kim S. M. et al., 2017), Stigmasterol (Haque and Moon, 2018), β-Sitosterol (Kim et al., 2008), Spinasterol (Jeong et al., 2010), Ellagic acid (Baluchnejadmojarad et al., 2017), Ferulic acid (Haque et al., 2015), p-Coumaric acid (Vauzour et al., 2010), 4-Hydroxybenzoic acid (Winter et al., 2017), Chlorogenic acid (Singh et al., 2018), and Ionone (Ma et al., 2014) which were previously been reported from Alternanthera sessilis (L.) R.Br. ex DC., may be responsible for the antiparkinsonian activity.

Antiprotozoal Activity

Koolen and the team had isolated compounds like Alternamide A-B and Alternamine A-B from the aerial parts of Alternanthera littoralis P.Beauv. and evaluated for their antiprotozoal activity againt protozoal strains viz. Trypanosoma cruzi trypomastigotes and Leishmania amazonensis. They had observed that out of all the tested compounds, Alternamine A was the most efficient one (Koolen et al., 2017).

Antispasmodic Activity

Garín-Aguilar and the team had antispasmodic activity of aqueous, hexane, methanolic extract, and fractions of methanol extract (F₁-F₆) obtained from the leaves of Alternanthera sessilis (L.) R.Br. ex DC. (Garín-Aguilar et al., 2013). while Saqib and Janbaz had used 70% ethanolic extract of the whole plant and its dichloromethane, aqueous fractions (Saqib and Janbaz, 2016). They had observed that Alternanthera sessilis (L.) R.Br. ex DC. possesses significant antispasmolytic activity. Phytomolecules like Vitexin and vitexin analogs (Ragone et al., 2007), Quercetin and quercetin analogs (Lozoya et al., 1994; Morales et al., 1994), Acacetin analogs (González-Trujano et al., 2012), Stigmasterol (Ammar et al., 2009), β-Sitosterol (Rehman et al., 2012), and Ellagic acid (Krenn et al., 2011) which were previously been reported from Alternanthera sessilis (L.) R.Br. ex DC., may be the contributors towards the antispasmodic activity of the extracts.

Antiviral Activity

Rattanathongkom and the team had isolated Chikusetsusaponin IVa isolated from the whole plant of Alternanthera philoxeroides (Mart.) Griseb. and evaluated antiviral activity against various viral cell lines through in vitro and in vivo assays. They had observed the dose-dependent activity along with the potential of Chikusetsusaponin IVa in inhibiting the viral protein synthesis (Rattanathongkom et al., 2009).

Central-Stimulating Activity

Mondal and the team had evaluated the central stimulating potential of the ethanolic extract obtained from the leaves of Alternanthera sessilis (L.) R.Br. ex DC. Results were quite significant (Mondal et al., 2014). Phytoconstituents acting on GABA receptors like Ricinoleic acid (Witt et al., 2002), Chlorogenic acid (Hara et al., 2014), p-Coumaric acid (Scheepens et al., 2014), Ferulic acid (Cheng et al., 2010; Sonar et al., 2019), Ellagic acid (Girish et al., 2013), Spinasterol (Socała et al., 2015), Stigmasterol (Karim et al., 2021), Acacetin analogs (Gálvez et al., 2015), Vitexin and vitexin analogs (Zhu et al., 2016; de Oliveira et al., 2020), and Quercetin and quercetin analogs (Goutman and Calvo, 2004; Kim et al., 2014) which were previously been reported from Alternanthera sessilis (L.) R.Br. ex DC., may be behind this GABA receptor mediated central-stimulating activity.

Gastrointestinal Protective Activity

Astudillo-Vázquez and the team had evaluated the gastrointestinal protective potential of the aqueous and ethanolic extracts obtained from the whole plant of Alternanthera sessilis (L.) R.Br. ex DC. They noticed that the antidiarrheal property i.e. decreasing the gastrointestinal content is the major factor behind the gastrointestinal protective activity of Alternanthera sessilis (L.) R.Br. ex DC. (Astudillo-Vázquez et al., 2008). Phytomolecules like Vitexin and vitexin analogs (Figer et al., 2017), Kaempferol and kaempferol analogs (Beber et al., 2017; Campos-Vidal et al., 2021), Quercetin and quercetin analogs (de la Lastra et al., 1994), Stigmasterol (Sánchez-Mendoza et al., 2008), β-Sitosterol (Sánchez-Mendoza et al., 2008), Ellagic acid (Beserra et al., 2011), Ferulic acid (Shahid et al., 2018), p-Coumaric acid (Panda and Suresh, 2015), Chlorogenic acid (Ahmed et al., 2021), and β-Carotene (Mózsik et al., 1996) which were earlier reported from Alternanthera sessilis (L.) R.Br. ex DC., may be responsible for this gastrointestinal protective potential.

Hepatoprotective Activity

Lin and the team had evaluated the hepatoprotective activity of the aqueous extract obtained from the whole plant of Alternanthera sessilis (L.) R.Br. ex DC. (Lin et al., 1994). while Bhuyan and the team had evaluated the hepatoprotective potential of the methanolic extract obtained from the whole plant (Bhuyan et al., 2017). Both these independent researches finally concluded that the Alternanthera sessilis (L.) R.Br. ex DC. is hepatoprotective. Phytomolecules like Vitexin and vitexin analogs (Duan et al., 2020), Kaempferol and kaempferol analogs (Wang M. et al., 2015; Wang et al., 2015c), Quercetin-3-methyl ether (Tseng et al., 2012), Quercetin and quercetin analogs (Miltonprabu et al., 2017), Acacetin analogs (Cho H.-I. et al., 2014), Stigmasterol (Carter et al., 2007), β-Sitosterol (Abdou et al., 2019), Ellagic acid (Girish and Pradhan, 2012), Ferulic acid (Rukkumani et al., 2004), p-Coumaric acid (Parvizi et al., 2020), 2,5-Dihydroxybenzoic acid (Pujari and Bandawane, 2021), Chlorogenic acid (Chen et al., 2019), and β-Carotene (Manda and Bhatia, 2003) which were previously reported from Alternanthera sessilis (L.) R.Br. ex DC., may be the contributory constituents towards the elicited hepatoprotective activity.

Immunomodulatory Activity

Several research teams had independently assessed the immunomodulatory potential of Alternanthera sessilis (L.) R.Br. ex DC.: Biella and the team had used aqueous extract of the whole plant (Biella et al., 2008); Guerra and the team had used aqueous extract of aerial parts (Guerra et al., 2003); while Moraes and the team had used aqueous and ethanolic extract of leaves as well as tetrahydrofuran, dichloromethane, aqueous, petroleum ether soluble fraction (Moraes et al., 1994). These studies validated the immunomodulatory property of Alternanthera sessilis (L.) R.Br. ex DC. Phytomolecules like Vitexin and vitexin analogs (Rosa et al., 2016), Kaempferol and kaempferol analogs (Lin et al., 2011; Swarnalatha et al., 2015), Quercetin-3-methyl ether (Martino et al., 2016), Quercetin and quercetin analogs (Manjunath and Thimmulappa, 2021), Acacetin analogs (Zhao et al., 2014), Stigmasterol (Antwi et al., 2017b), β-Sitosterol (Desai et al., 2009), Ellagic acid (Abuelsaad et al., 2013), Ferulic acid (He F. et al., 2021), p-Coumaric acid (Pragasam et al., 2012), Chlorogenic acid (Guo et al., 2021), and β-Carotene (Jyonouchi et al., 2009) which were previously been reported from Alternanthera sessilis (L.) R.Br. ex DC., may be responsible for this immunomodulatory potential.

Moraes and the team had also evaluated the immunomodulatory activity of aqueous and ethanolic extract of leaves as well as tetrahydrofuran, dichloromethane, aqueous, petroleum ether soluble fractions obtained from Alternanthera brasiliana (L.) Kuntze and Alternanthera littoralis P.Beauv. (Moraes et al., 1994). Phytomolecules like Vitexin and vitexin analogs (Rosa et al., 2016), Kaempferol and kaempferol analogs (Lin et al., 2011; Swarnalatha et al., 2015), Quercetin and quercetin analogs (Manjunath and Thimmulappa, 2021), Tricin (Santos et al., 2017), Stigmasterol (Antwi et al., 2017b), β-Sitosterol (Desai et al., 2009), Ferulic acid (He F. et al., 2021), p-Coumaric acid (Pragasam et al., 2012), and Chlorogenic acid (Guo et al., 2021) which were previously reported from Alternanthera brasiliana (L.) Kuntze, may be responsible towards its immunomodulatory activity. Phytomolecules like Vitexin and vitexin analogs (Rosa et al., 2016), Kaempferol (Lin et al., 2011; Swarnalatha et al., 2015), Quercetin-3-methyl ether (Martino et al., 2016), Quercetin and quercetin analogs (Manjunath and Thimmulappa, 2021), Acacetin analogs (Zhao et al., 2014), Stigmasterol (Antwi et al., 2017b), and Hydroxytyrosol (Shan and Miao, 2022) which were previously reported from Alternanthera littoralis P.Beauv., may be responsible for its immunomodulatory activity.

Insecticidal Property

Coutinho and the team had evaluated the insecticidal potential of the ethanolic extract obtained from the leaves of Alternanthera brasiliana (L.) Kuntze. against Drosophila melanogaster (Harwich strain). They found that the tested concentrations of the ethanolic extract were having a mild insecticidal effect, and that too after 24–48 h exposure (Coutinho et al., 2017). Phytomolecules like Kaempferol and kaempferol analogs (Zhang et al., 2016), Quercetin and quercetin analogs (Mesbah et al., 2007), Stigmasterol (Gade et al., 2017), β-Sitosterol (Zolotar et al., 2002), Spinasterol (Ahmed et al., 2020), and Ferulic acid (Yang et al., 2017) which were previously isolated from Alternanthera brasiliana (L.) Kuntze., may be responsible for this insecticidal property.

Lithotriptic/Antiurolithiatic Activity

Dhanya and the team had evaluated the antiurolithiatic activity of Kalka—fine paste of macerated fresh plant material of Alternanthera sessilis (L.) R.Br. ex DC. while Babu and the team had used ethanolic extract of the whole plant for the assessment of antiurolithiatic activity (Dhanya et al., 2017; Babu et al., 2021). Results obtained by both these independent studies are quite significant and reflects the potential of Alternanthera sessilis (L.) R.Br. ex DC. as lithotriptic agent. Phytomolecules like Kaempferol and kaempferol analogs (Cechinel-Zanchett et al., 2020), Quercetin and quercetin analogs (Dinnimath et al., 2017), Stigmasterol (Lobine et al., 2020), and Ferulic acid (Zhao et al., 2019) which were previously been reported from Alternanthera sessilis (L.) R.Br. ex DC., may be responsible for this antiurolithiatic activity.

Larvicidal Activity

Babu and the team had also evaluated the larvicidal property of ethanolic extract obtained from the whole plant of Alternanthera sessilis (L.) R.Br. ex DC. They found that the ethanolic extract was having a dose dependent percent mortality against mosquito larvae (Babu et al., 2021). Phytomolecules like Stigmasterol (Gade et al., 2017), β-Sitosterol (Angajala and Subashini, 2018), and Ferulic acid (Pavela, 2011), which were earlier isolated from Alternanthera sessilis (L.) R.Br. ex DC., may be responsible behind this larvicidal activity.

Nootropic Activity

Gupta and Singh had evaluated the nootropic activity of methanolic extract obtained from the leaves of Alternanthera sessilis (L.) R.Br. ex DC. And results were quite promising (Gupta and Singh, 2012b). Phytomolecules like Kaempferol and kaempferol analogs (Das et al., 2018), Quercetin and quercetin analogs (Halder et al., 2015), Ellagic acid (Bansal et al., 2017; Kiasalari et al., 2017), and Ferulic acid (Yang et al., 2016; Mhillaj et al., 2017) which had been previously isolated from Alternanthera sessilis (L.) R.Br. ex DC., may be the contributing phytomolecules towards this nootropic activity.

Photoprotective Activity

Alencar Filho and the team had evaluated the photoprotective effect of the gel prepared from 5% w/w of extract Alternanthera brasiliana (L.) Kuntze enriched in flavonoids. They had observed that the stabilization of the ROS and resonating permission are the mechanisms behind this photoprotective activity of the gel extract (Alencar Filho et al., 2020). Phytomolecules like Kaempferol and kaempferol analogs (Monici et al., 1994), Quercetin and quercetin analogs (Saija, 2003; Gonçalves et al., 2019), Tricin (Moon et al., 2018), Stigmasterol (Bayer et al., 2011), β-Sitosterol (Bayer et al., 2011), Ferulic acid (Lin et al., 2005; Peres et al., 2018), p-Coumaric acid (Biswas et al., 2021), and Chlorogenic acid (Wang et al., 2021) which were earlier reported from Alternanthera brasiliana (L.) Kuntze, may be responsible for this photoprotective property of the gel extract.

Sedative Property

Oyemitan and the team had evaluated the sedative action of the ethanolic extract obtained from the leaves of Alternanthera brasiliana (L.) Kuntze. They had observed that the ethanolic extract was expressing the sedative property by acting on stimulatory or central excitatory channels (Oyemitan et al., 2015). Phytomolecules like Quercetin and quercetin analogs (Nakhaee et al., 2021), β-Sitosterol (Aguirre-Hernández et al., 2007), and Ferulic acid (Tu et al., 2012) which were previously been reported from Alternanthera brasiliana (L.) Kuntze., may be responsible for this sedative action.

Wound Healing Property

Barua and the team had reported several studies validating the wound healing property of Alternanthera brasiliana (L.) Kuntze (Barua et al., 2009; Barua C. et al., 2012; Baru et al., 2012; Barua C. C. et al., 2012). Phytomolecules like Vitexin and vitexin analogs (Bektas et al., 2020), Kaempferol and kaempferol analogs (Petpiroon et al., 2015; Özay et al., 2019), Quercetin and quercetin analogs (Gomathi et al., 2003), Tricin (Han et al., 2016), β-Sitosterol (Abbas et al., 2019), Ferulic acid (Ghaisas et al., 2014), p-Coumaric acid (Kong et al., 2013; Boeing et al., 2020), and Chlorogenic acid (Bagdas et al., 2015) which had been isolated from Alternanthera brasiliana (L.) Kuntze previously, may be responsible for this wound healing property.

Muniandy and the team had evaluated the wound healing action of the 90% hydroethanolic extract obtained from the stem of Alternanthera sessilis (L.) R.Br. ex DC. while Jalalpure and the team had used chloroform extract obtained from the leaves Alternanthera sessilis (L.) R.Br. ex DC. Both these teams had independently ascertained the wound healing property of Alternanthera sessilis (L.) R.Br. ex DC. (Jalalpure et al., 2008; Muniandy et al., 2018b). Phytomolecules like Vitexin and vitexin analogs (Bektas et al., 2020), Kaempferol and kaempferol analogs (Petpiroon et al., 2015; Özay et al., 2019), Quercetin and quercetin analogs (Gomathi et al., 2003), Acacetin analogs (Bhat et al., 2013), β-Sitosterol (Abbas et al., 2019), Ellagic acid (Mo et al., 2014), Ferulic acid (Ghaisas et al., 2014), p-Coumaric acid (Kong et al., 2013; Boeing et al., 2020), and Chlorogenic acid (Bagdas et al., 2015), β-Carotene (Gerber and Erdman, 1982), and Ricinoleic acid (Nada et al., 2018) which had earlier reported from Alternanthera sessilis (L.) R.Br. ex DC., may be responsible for this wound healing property.

After this exhaustive cross-literature review for the bioactive compounds that may be responsible elements behind the potent pharmacological actions elicited by the extracts, we have summarized those in a smart interactive illustration (Figure 4).

FIGURE 4

FIGURE 4. Bioactive Molecules and their elicited pharmacological activities. This information was collected as a cross-sectional literature review while exploring the possible bioactive molecules behind the pharmacological activities of the crude extracts obtained from various species of Alternanthera Genus.

It is indispensable to confirm if traditional claims of Alternanthera species have been proven by systematic scientifically designed pharmacological (preclinical or clinical) studies. Traditional claims and reported pharmacological activities of various species are presented in Table 3, and observations are as follows:

a) Traditional claims of some species (Alternanthera brasiliana (L.) Kuntze, Alternanthera caracasana Kunth, A. dentata (now reclaimed as Alternanthera brasiliana (L.) Kuntze), A. ficoides (now reclaimed as Alternanthera sessilis (L.) R.Br. ex DC.), Alternanthera littoralis P.Beauv., A. maritima (now reclaimed as Alternanthera littoralis P.Beauv.), Alternanthera nodiflora R.Br., Alternanthera paronychioides A.St.-Hil., Alternanthera porrigens (Jacq.) Kuntze, Alternanthera pungens Kunth, Alternanthera sessilis (L.) R.Br. ex DC., A. tenella (now reclaimed as Alternanthera sessilis (L.) R.Br. ex DC.), and A. triandra (now reclaimed as Alternanthera sessilis (L.) R.Br. ex DC.)) have not been validated scientifically.

b) Traditionally used species like Alternanthera caracasana Kunth and Alternanthera porrigens (Jacq.) Kuntze have not been investigated for any pharmacological activities. These species hold great potential for future research intending to validate traditional claims.

c) Species (Alternanthera brasiliana (L.) Kuntze, Alternanthera paronychioides A.St.-Hil., Alternanthera philoxeroides (Mart.) Griseb., and Alternanthera sessilis (L.) R.Br. ex DC.) have been screened for those pharmacological actions which are not claimed traditionally. These species may have been chosen following a chemotaxonomical or ecological approach.

d) Literature did not reveal any traditional use of three species (Alternanthera bettzickiana (Regel) G.Nicholson, Alternanthera hirtula (Mart.) R.E.Fr., and Alternanthera praelonga A.St.-Hil.) but evaluated for varied pharmacological activities.

TABLE 3

TABLE 3. Relationship between reported scientific pharmacological activities of Alternanthera species and their traditional claims.

Toxicological Studies

Hydroalcoholic extract of Alternanthera brasiliana (L.) Kuntze and Alternanthera bettzickiana (Regel) G.Nicholson leaves was orally administered (200 mg/kg dose) for 14 days in mice to observe any change in behavior of animals (Kasthuri and Ramesh, 2018). Further, hematological and histopathological changes were also observed. Sub-acute toxicity study suggested that both extracts samples did not show any harmful side effects. Hydroethanolic leaf extract of Alternanthera bettzickiana (Regel) G.Nicholson displayed a progressively powerful cytotoxic impact on DLA cell lines than Alternanthera brasiliana (L.) Kuntze extract.

The oral acute toxicity study was conducted on 95% ethanolic extract of Alternanthera philoxeroides (Mart.) Griseb. at the dose of 500 mg/kg in male and female rodents (Thanabhorn et al., 2005). The ethanolic extract did not show mortality and gross morphological alterations in the organs of rodents. Oral administration of 1,000 mg/kg/day for 14 days showed no significant changes in the body and inner organs weights, hematological and clinical parameters.

Clinical Studies

The studies have shown antiretroviral activity of Alternanthera pungens Kunth herbal tea due to antioxidant potential when administered to HIV patients (Djohan et al., 2009). Blood samples were taken from fasted patients who received an Alternanthera pungens Kunth tea for 12 months every day before dinner. The markers of oxidative stress (malondialdehyde and advanced oxidation protein end products), plasma T lymphocytes, transaminases, and creatinine were determined in the blood sample. A significant decrease in concentrations of markers of oxidative stress and an increase in plasma levels of CD4 and CD8 T cells after this period were observed. Further, no signs of hepatic and renal toxicity were seen in HIV patients.

In another case study, the potential of Alternanthera sessilis (L.) R.Br. ex DC., Momordica charantia L., and Colocasia esculenta (L.) Schott were investigated in reducing postprandial blood glucose levels in healthy human subjects and patients with type II diabetes (Bachok et al., 2014). The results of the clinical report suggested that Alternanthera sessilis (L.) R.Br. ex DC. reduced the non-significant glucose level in 3 h in comparison to standard control diet in healthy and diseased subjects. This case study was conducted in India with eight healthy subjects and six diabetic subjects.

Conclusion

Scrutiny of available literature reveals that out of 139 species of the genus Alternanthera:

a) Nine species have been investigated phytochemically,

b) Fifteen species possess strong ethnopharmacological records,

c) Twelve species have been scientifically evaluated in the in vitro or in vivo experimental models for various pharmacological activities,

d) Three species have been subjected to toxicity studies for establishing safety profiles,

e) Two species have been examined for clinical studies.

To date, 129 compounds have been isolated from 9 species of Alternanthera. 129 bioactive compounds were classified in 11 phytochemical classes, covering information about 40 flavonoids, 17 triterpenoid/saponins, 15 sterols, 12 alkaloids, 10 phenolic compounds, 3 ionone, 1 benzopyran, 3 hydroxycinnamic acids, 4 anthraquinone, 8 volatile oils and 17 miscellaneous compounds. Flavonoids (∼32%) constitute the main class of phytoconstituents in the genus Alternanthera followed by triterpenoids (∼13%). The isolated triterpenoids such as oleanolic acid, ursolic acid, and flavonoids such as luteolin, apigenin, vitexin, kaempferol, quercetin aglycones and their glycosides from the genus have proven therapeutic value. In terms of the phytochemical exploration, the most explored species of Alternanthera genus were Alternanthera philoxeroides (Mart.) Griseb. (52 compounds), Alternanthera sessilis (L.). R.Br. ex DC. (45 compounds), Alternanthera brasiliana (L.). Kuntze (32 compounds), and Alternanthera littoralis P.Beauv (24 compounds). Alternanthera sessilis (L.) R.Br. ex DC. has so far yielded a diverse class of compounds, like benzopyran, flavonoids, sterols, triterpenoid/saponin, phenolic compounds, ionone, and miscellaneous compounds. Similarly, Alternanthera philoxeroides (Mart.) Griseb. has also yielded a diverse class of compounds like flavonoids, sterols, triterpenoid/saponins, phenolic compounds, anthraquinone, alkaloids, and miscellaneous compounds.While volatile oil related compounds were extracted only from Alternanthera pungens Kunth, ionone analogues were isolated from Alternanthera sessilis (L.) R.Br. ex DC. only and hydroxycinnamic acids were reported only from Alternanthera bettzickiana (Regel) G.Nicholson. Researchers could explore rest of the species of Alternanthera genus to check if containing ionone analogues, volatile oils, and hydroxycinnamic acids. Further, the species of Alternanthera genus which were least explored in terms of phytochemical characterization is also leading for possible opportunities for the researchers.

To the best of our knowledge, the phytochemial characterization of Alternanthera paronychioides A.St.-Hil., Alternanthera caracasana Kunth, Alternanthera nodiflora R.Br., and Alternanthera ficoidea (L.) P.Beauv. was not yet done, leaving an ample scope for the researchers.

Some phytoconstituents like quercetin, vitexin, chlorogenic acid, kaempferol, ferulic acid, β-sitosterol, p-coumaric acid, caffeic acid, quinic acid, etc had been reported from more than one species of Alternanthera. Probably, we could say that these phytoconstituents may be common secondary metabolites in Alternanthera genus. So, we recommend the researchers to explore the rest of the Alternanthera species for these common metabolites. These metabolites could serve as biomarkers for them.

As twelve species of Alternanthera have been investigated scientifically for pharmacological activities, only 9 species of the genus have been explored phytochemically. Few medicinally promising Alternanthera species have not been taken into consideration for phytochemical studies. The existing literature demonstrates that 5 species of genus Alternanthera such as.

Alternanthera brasiliana (L.) Kuntze, Alternanthera caracasana Kunth, Alternanthera ficoidea (L.) P.Beauv., Alternanthera nodiflora R.Br., and Alternanthera paronychioides A.St.-Hil. have been scientifically reported to exhibit various pharmacological activities, but these species have never been subjected to bioactivity directed fractionation to isolate bioactive phytoconstituents using appropriate chromatographic techniques. Therefore, natural product scientists should expand their research activities on Alternanthera species to isolate more bioactive compounds which can be developed as safer and efficacious lead molecules or potent analogs of bioactive markers. Further, it seems necessary to mention a major research gap in phytochemical studies that no emphasis has been given to standardizing these plants based on marker compounds. Appropriate analytical methods need to be developed using HPLC, HPTLC, or LC-MS for the standardization of Alternanthera species. Molecular docking and QSAR studies on selective bioactive markers of these species are also lacking. It has been observed that crude uncharacterized extracts of Alternanthera species have been used in most pharmacological studies. This observation attracts attention towards the isolation of bioactive compounds from Alternanthera following the bioactivity-guided fractionation approach. Highlighting a mechanistic approach for pharmacological activities is another area of research to be covered. Alternamide A-B and Alternamine A-B were evaluated only for antiprotozoal activity while Chikusetsusaponin IVa was checked for antiviral activity only, leaving a wide scope for the researchers.

Amongst 139 species of Alternanthera, only 12 species have shown medicinal value in preclinical studies, and out of these only Alternanthera pungens Kunth and Alternanthera sessilis (L.) R.Br. ex DC. have been investigated clinically for antiretroviral and antidiabetic activities, respectively. The toxicity studies have been conducted on 3 species such as Alternanthera bettzickiana (Regel) G.Nicholson, Alternanthera brasiliana (L.) Kuntze, and Alternanthera philoxeroides (Mart.) Griseb. to establish their safety profile. Please be noted that as per the latest guidelines and recommendations of the ethnopharmacology team, the scientific names of the plants have been reassessed and considered the name given on https://mpns.science.kew.org/mpns-portal/. So the universally recognized name has been mentioned rather than the synonym indicated in the cited articles.

It is finally concluded that a well-planned roadmap of research activities is needed to be designed on traditionally used and medicinally promising plants of genus Alternanthera, so that their products and preparations may emerge out to be clinically potential and safe medicines in the treatment of various ailments.

Author Contributions

RM and BS contributed to the conception and design of the study. RS, VD, DK, SB, MB, SK, AD, and SS wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

Funding

This work was supported by the National Natural Science Foundation of China (32070671), the COVID-19 Research Projects of West China Hospital Sichuan University (Grant no. HX-2019-nCoV-057), and the Regional Innovation Cooperation between Sichuan and Guangxi Provinces (2020YFQ0019).

Author Disclaimer

The scientific name of plants was mentioned as per the universally accepted nomenclature, specified and recommended by the Ethnopharmacology team. So, the names specified in the manuscript will seems to be different from that of cited articles. To cross-check the nomenclature, refer https://mpns.science.kew.org/mpns-portal/.

Conflict of Interest

RS and SS are having honorary based association with iGlobal Research and Publishing Foundation, New Delhi India, who declare that there are no conflicts of interest.

The remaining 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.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

The authors acknowledge the financial support received from the National Natural Science Foundation of China, the West China Hospital Sichuan University, and the Regional Innovation Cooperation between Sichuan and Guangxi Provinces.

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