Introduction

The liver is a crucial organ inside the human body, playing a pivotal role in the regulation of several physiological processes and activities associated with metabolism, synthesis, secretion, and storage. The process in question assumes a pivotal function in the removal of drugs and the detoxification of both endogenous waste metabolites and foreign hazardous chemicals. To date, a diverse range of etiologies has been reported for over one hundred well-known liver illnesses (Melaram 2021). Chronic liver dysfunction or damage is a significant global health concern. Chronic liver disease comprises a diverse array of liver diseases, such as fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (Hong et al. 2015).

Liver disease is responsible for an estimated 2 million deaths annually on a global scale. Out of these, roughly 1 million deaths are attributed to complications arising from cirrhosis, while the remaining 1 million deaths are associated with viral hepatitis and hepatocellular carcinoma (HCC) (Sharma and Nagalli 2021; Asrani et al. 2019). The primary etiologies of hepatic disease commonly encompass infectious agents such as viral hepatitis A, B, and C, as well as fatty liver, xenobiotics including alcohol, drugs, and chemicals, hereditary and genetic abnormalities, and autoimmune hepatitis (Beier and Arteel 2021). In previous studies, it has been seen that the liver can be affected by disease-causing substances, which have the ability to trigger the production of reactive oxygen species (ROS). This, in turn, can result in the development of inflammation, necrosis, and even cancer (He et al. 2017; Khoury et al. 2015). During the initial phases, the liver undergoes a process of repairing any impairments or malfunctions it may have. However, when damage is repeatedly or persistently inflicted, it initiates liver fibrosis, a condition that advances to cirrhosis and finally culminates in the development of hepatocellular carcinoma (HCC) (Llovet et al. 2022; Dhar et al. 2020). According to the European Association for the Study of the Liver (EASL 2018), the majority of hepatocellular carcinoma (HCC) cases, exceeding 90%, are attributed to chronic liver disease. Notably, cirrhosis emerges as the most significant risk factor for HCC. This association imposes a substantial burden of cancer-related mortality, with HCC estimated to rank as the fourth leading cause of cancer death globally (Fitzmaurice et al. 2017). This prevalence is observed across various regions worldwide. (See Fig. 1 for visual representation of HCC’s ranking in cancer-related deaths).

Fig. 1
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Global burden of liver cirrhosis and HCC

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In the year 2017, the global mortality rate due to cirrhosis was recorded at 1.32 million deaths among females and 0.883 million deaths among males. This represents an increase in mortality compared to the year 1990, when a lower death rate was seen. Although there has been a rise in the total number of fatalities, it is noteworthy that the age-standardized mortality rate exhibited a decline from 21.0 per 0.1 million people in 1990 to 16.5 per 0.1 million population in 2017. According to Sepanlou et al. (2020), there was a continuous disparity in mortality rates between males and females throughout all seven continents, including Asia, Africa, North America, South America, Antarctica, and Australia, during the period spanning from 1990 to 2017.

In recent decades, there has been a suggestion that the etiology of hepatocellular injury is not solely attributed to the injurious agent itself, but also involves drug-associated inflammatory cells that are targeted by stressed hepatocytes, leading to the development of cirrhosis and hepatocellular carcinoma (Anandasadagopan et al. 2017). The primary etiologies of hepatic illness encompass infectious agents such as viral hepatitis A, B, and C, hepatic steatosis, xenobiotics including alcohol, drugs, and chemicals, hereditary and genetic disorders, and autoimmune hepatitis (Beier and Arteel 2021). During the initial phases, the liver undergoes a reparative process to address any damage or dysfunction. However, in cases of repeated or persistent injury, this can initiate liver fibrosis, a condition that advances to cirrhosis and ultimately culminates in the development of hepatocellular carcinoma. Exposure of the liver to hazardous substances, environmental pollutants, and medications can induce cellular damage by means of metabolic activation of reactive oxygen species (ROS), resulting in hepatocyte inflammation, necrosis, and oxidative stress (Khoury et al. 2015). Hepatotoxicity is a condition characterized by impaired liver function or liver damage resulting from an excessive exposure to pharmaceuticals or xenobiotics, including but not limited to acetaminophen, cadmium chloride, ethanol/alcohol, carbon tetrachloride (CCl4), and allyl alcohols (Navarro and Senior 2006). Liver toxicity has detrimental effects on multiple physiological processes, such as metabolism. The liver is particularly susceptible to harm compared to other organs due to its pivotal role in metabolism and its capacity to concentrate and convert xenobiotics (Bediet al. 2016; Kumar et al. 2015).

Different herbal products have already been used for the management of liver diseases in some countries or regions. The review of literature collected for more than twenty years indicates that various medicinal plant extracts and their isolated compounds are used to treat liver disease. For example: Nigella sativa seed oil has potential hepatoprotective activity (Burits and Bucar 2000), Brucea javanica fruit extract has been shown to possess antiproliferative and apoptotic activities on HepG2 (Lau et al. 2008), Acanthus ilicifolius leaf extract produced significant inhibition against HCC cells (Singh et al. 2009), aqueous extract of Artemisia vulgaris exerted an inhibitory effects on cell growth and apoptosis (Nawab et al. 2011), aerial part of Dracocephalum kotschyl has a potential anticancer activity on liver cancer cell (Talari et al. 2014), isolated phytocompounds of Phyllanthus niruri possess hepatoprotective properties (Amin et al. 2012), methanolic root extract and isolated compound (Glycyrrhizin) of Glycyrrhiza uralensis have inhibitory nature on HCC (Adianti et al. 2014; Wahyuni et al. 2016), Trichosanthes dioica fruit peel extract prevents hepatic inflammation and induced hepatic fibrosis (Khan et al. 2020). Many well-known phytocompounds such as taxanes (docitaxel, paclitaxel), vinca alkaloids (vinblastine, vincristine, vinorelbine), pomiferin, histone deacetylase inhibitor, 9-bromo-noscapine, bromelain, podophyllotoxins (topotecan,irinotecan) as well as epipodophyllotoxins, homoharringtonine, ellipticine are showing anticancer activity (Devi et al. 2019).

In the context of India, it is observed that a significant majority, specifically over 65% of the populace, predominantly relies on traditional medicine as their primary means of addressing their healthcare requirements. According to several estimates, it has been indicated that around 80% of pharmacological molecules originate from natural sources. Additionally, it has been predicted that 50% of these pharmaceuticals have received approval since the year 1994 (Pandey et al. 2013). The ethno-medicinal techniques of India and Chinese systems involve the utilization of many medicinal plants and their formulations to address liver diseases. According to recent research findings, it has been indicated that the use of raw herbs or herbal products can potentially yield tangible health advantages when employed over an extended period of time (Sen and Chakraborty 2015). Desmodium is a very varied genus within the Fabaceae family, encompassing over 350 species that are primarily found in tropical and subtropical regions worldwide (Ma et al. 2011a, b). Within the Chinese territory, a total of 28 species from this genus can be found, with over 20 of these species having a significant historical background in their application as medicinal resources within the realm of Traditional Chinese Medicines (TCMs) (Li et al. 2008). In addition to China, the herbs belonging to this genus are also found abundantly in India and have been widely utilized in Ayurveda, a traditional medicinal system, for the treatment of various diseases (Kirtikara et al. 2001; Rastogi et al. 2011). These herbs have been recognized for their diverse traditional medicinal properties and have been the subject of extensive research, resulting in the identification of over 200 specialized metabolites, including flavonoids, alkaloids, steroids, terpenoids, and phenylpropanoids. While numerous constituents have been isolated from this genus, only a limited number of phytoconstituents have undergone evaluation to determine their biological activity. The investigation of the bio-activities of medicinal plants is of utmost importance in substantiating traditional assertions and discovering untapped bio-active properties, particularly in light of the increasing worldwide fascination with natural goods possessing significant therapeutic capabilities (Perera et al. 2018). Plant-based pharmaceuticals and bioactive components possess considerable economic potential within the health care and pharmaceutical sectors due to their natural composition, enhanced tolerability, and non-toxicity towards normal human cells (Shah et al. 2013).

In recent decades, there has been a significant surge in research pertaining to the chemical compounds derived from Desmodium species and their corresponding biological activities. Consequently, this research aims to elucidate the conventional applications, chemical composition, pharmacological properties, and bioactivity of many intriguing molecules derived from the Desmodium genus, in addition to providing a comprehensive compilation of all identified specialized metabolites isolated from this species to date.

Methodology

The data collected for this review is derived from a comprehensive exploration of the medical, distribution, mechanism of action, chemistry, bioactive chemicals, biological, and pharmacological characteristics of the Desmodium genus. The researchers conducted a comprehensive literature review using various online databases, including Google Scholar, Science Direct, Scopus, Wiley Online Library, Web of Science, Encyclopedia of Life (eOL), and Plants of the World Online (Kew Science). The IUCN Red List Categories and Criteria method is a globally recognized evaluation method that categorizes species into many classifications based on straightforward quantitative guidelines (IUCN, 2006). Subsequently, the search outcomes were further narrowed down by employing the following keywords: Desmodium, ethano-pharmacological, antioxidant, anti-inflammatory, hepatitis, antihepatic fibrosis, hepatoprotective effect, and hepatosplenomegaly. The ChemDraw software is utilized to replicate chemical structures of compounds obtained from the PubChem database, accessible at http://pubchem.ncbi.nlm.nih.gov/search/search.cgi. This review focused on the examination of endangered Desmodium species, with an emphasis on phytochemical, pharmacological, and toxicological investigations. The findings of this study provide valuable insights that can guide future research efforts aimed at improving the hepatic sustained and holistic therapeutic development of Desmodium.

Geographical distribution

Desmodium Desv. is a genus in the flowering plant, family Fabaceae or Leguminoseae, sometimes called as tick-trefoil, tick clover, hitch hikers (White ILDIS, UK 2005) and it includes around 350 species worldwide (Liguo et al. 2008). The member of the genus Desmodium contains 170 tropical and subtropical species (Trout 1997) and they are widely distributed throughout Asia–Temperate, Asia-Tropical, Indo-China, Thailand and Europe (‘Taxonomy–GRIN –Global Web v 1.10.3.6’, 2018). Most diverse in SE Asia and Mexico to S America, occurring from Africa-Madagascar (40 spp. 15 endemic), China to Temperate E Asia (35 spp 10 endemic) (POWO 2022) and nearly 20 species have a long history of mediation in Traditional Chinese Medicine (TCM), Mexico (80 spp, 50 endemic), Central America, Caribbean and tropical to subtropical S America (80 spp, 50 endemic), According to Hooker’s “Flora of British India” [1879, 1999 (reprint)], 49 species of Desmodium were recorded. Shah (1987) in his “Flora of Gujarat State” provided the first comprehensive description of Desmodium species in Gujarat recording and found 14 species later on Raghavan et al. 1981 listed 15 Desmodium species in their checklist as plants of Gujarat. Figure 2a represents the geographical distribution of Desmodium plant species. Country-level geographical distribution and the conservation status of Desmodium plant species were analyzed from 1730–2022 using IUCN Red List Categories and Criteria system which are represented in Fig. 2b and 2c,respectively. According to IUCN Desmodium pseudoamplifolium Micheli and Pleurolobus lobatus (Schindl.) H. Ohashi & K. Ohashi have been assessed as Critically Endangered species (CR), Desmodium kaalense Guillaumin and, Desmodium harmsii (Schindl.) H. Ohashi & K. Ohashi (synonym of: Grona harmsii (Schindl.) H. Ohashi & K. Ohashi) are categorized as Endangered species (EN) and Eleiotis rottleri Wight & Arn. is listed as Vulnerable species (VU) and threatened species in 2010 (Fig. 2d).

Fig. 2
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a Geographical distribution of Desmodiumplant species. b country level geographical distribution of Desmodium species (1730–2022). c Conservation status ofDesmodium species (1730–2022). d pie-chart showing the percentage number of species in Critically Endangered (CR), Endangered (EN) and Vulnerable (VU) categories

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Phytochemical constituents present in Desmodium species

The genus Desmodium is rich in 81 flavonoids, 40 alkaloids, 14 terpenoids, 13 steroides, 10 phenols, 8 phenylpropanoids, 2 glycosides and a number of volatile oils that has a broad spectrum of secondary metabolite classes have been isolated and identified (Ma et al. 2011a, b). The phytoconstituents have been mainly focused on the following 18 Desmodium species that are likely to provide a good foundation with well-documented utilities of plant products use as hepatoproctective agents. Desmodium caudatum (Thunb.) DC. (synonym of Ohwia caudate (Thunb.) H. Ohashi); Desmodium elegans DC. (synonym of Sunhangia elegans (DC.) H. Ohashi & K. Ohashi); Desmodium adscendens (Sw.) DC. (synonym of Grona adscendens (Sw.) H. Ohashi & K. Ohashi); Desmodium fallax Schindl. (synonym of Hylodesmum podocarpumsubsp. fallax (Schindl.) H. Ohashi & R.R. Mill); Desmodium gangeticum (L.) DC. (synonym of Pleurolobus gangeticum (L.) J.ST.-Hil. ex H. Ohashi & K. Ohashi); Desmodium gyrans (L.f.) DC. (synonym of Codariocalyx motorius (Houtt.) H. Ohashi); Desmodium heterocarpum (L.) DC. (synonym of Grona heterocarpos (L.) H. Ohashi & K. Ohashi); Desmodium longipes (Craib) Schindl. (synonym of Phyllodium longipes) (Craib) Schindl.; Desmodium microphyllum (Thunb.) DC. (synonym of Leptodesmia microphylla (Thunb.) H. Ohashi & K. Ohashi); Desmodium oblongumWall. exBenth. (synonym of Uraria oblonga (Wall. ex Benth.) H. Ohashi & K. Ohashi); Desmodium pulchellum Blume ex Miq. (synonym ofGrona heterocarposvar. Strigose (Meeuwen) H. Ohashi & K. Ohashi);Desmodium triflorum (L.) DC. (synonym of Grona triflora (L.) H. Ohashi & K. Ohashi), Desmodium triquetrum (L.) DC. (synonym of Tadehagi triquetrum (L.) H. Ohashi); Desmodium velutinum (Willd.) DC. (synonym of Polhillides velutina (Willd.) H. Ohashi & K. Ohashi); Desmodium styracifolium (Osbeck) Merr. (synonym of Grona styracifolia (Osbeck) H. Ohashi&K. Ohashi); Desmodium oojeinense (Roxb.) H. Ohashi (synonym of Ougeinia oojeinensis (Roxb.) Hochr.); Desmodium uncinatum (Jacq.) DC.; Desmodium cajanifolium (Kunth) DC. showed a wide spectrum of in vitro and in vivohepatoprotective activities that have emerged a good source in traditional Chinese and Indian system of medicine due to its detoxifying properties.

According to phytochemical investigationsflavonoids and alkaloids are the main metabolites in this genus. Different species isolated phytocompounds are reported (Table 1) with structural elucidation (Fig. 3a–i). Flavonoids, notably isoflavonoids, are abundant in Desmodium, including flavones, 7, 8 prenyl-lactone flavonoids, flavonols, flavan-3-ols, and flavanonols. Isoflavonoids include isoflavanones, pterocarpans, and coumaronochromone. A total list of 40 isolated alkaloid compounds from Desmodium sp. and characterized mainly as indole alkaloids along with phenylethylamine alkaloids, pyrrolidine alkaloids, amide alkaloids and alkylamine. In addition to flavonoids and alkaloids, a range of terpenoids, steroids, phenols, phenyl-propanoids, glycosides and volatile oils also been reported in this species (Ma et al. 2011a, b). A patent has been awarded on the use of Desmodium sp, especially D. adscendens (Tubéry and Tubéry 1989; Maes et al. 2020) as isolated compound D-pinitol for protecting the liver that is induced with both viral and chemically-induced hepatitis. There is an urge need for the isolation and identification of specialized metabolites that are responsible for their mode of action, bioavailability, pharmacokinetitcs and their physiological pathway with sufficient details.

Table 1 A comprehensive list of preclinical pharmacology of isolated phytoconstituents of different species of the genus Desmodium
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Fig. 3
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a Compounds isolated from D. heterophyllum (1–4). b Compound isolated from D. adscendens. c Compounds isolated from D. caudatum (6–13). d Compounds isolated from D. uncinatum (14–27). e Compounds isolated from D. styracifolium (28–43). f Compounds isolated from D. gangeticum (44–52). g Compounds isolated from D. blandum (53–60). h Compounds isolated from D. elegans (61 & 63). i Compounds isolated from D. velutinum (64–68)

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Production and marketing

Recently, there are some hepatoprotective drugs derived from different Desmodium species are commercially available in markets. Figure 4 depicts the products obtainedfrom Desmodium species such as homeopathic medicine, herbal tea, tonic and dietary supplement and there is an urge need for the isolation and identification of specialized metabolites that are responsible for their mode of action, bioavailability, pharmacokinetitcs and their physiological pathway with sufficient details.

Fig. 4
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Products derived from Desmodium species (a) traditional plant medicine in Central and South America D. molliculum (Manayupa) and D. adscendens, b) Homeopathic medicine product D. gangeticum, c and e Hepatic detoxifier D. adscendens, d and h Desmodium Herbal Tea helps the liver to cleanse and regenerate D. adsendens and D. gangeticum, f, g and i tonic and dietary supplement formulated with D. adscendens and vitamin C

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A general mechanism(s) of action of hepatocarcinogenesis

According to the findings of Hsu et al. (2019), hepatocellular carcinoma ranks as the fifth most prevalent malignant tumor globally and is the third major cause of cancer-related mortality. Agreeing to Sayiner et al. (2019), the continents of Asia and Africa exhibit higher incidence of hepatocellular carcinoma (HCC) compared to the continents of Europe and North America. Hepatocellular carcinoma (HCC) can be attributed to both endogenous and exogenous causes. These factors encompass many substances such as alcohol, drugs, polysaccharides, proteinaceous compounds, and lipids. Additionally, the presence of carcinogenic chemicals like diethylnitrosamine and N-Nitrosodimethylamine, as well as the usage of allopathic medications including paracetamol, diclofenac, erythromycin, oral contraceptives, among others, has been implicated in the development of HCC. According to Nasreen et al. (2018), increased consumption of certain dietary components leads to biotransformation in the liver, resulting in oxidative stress as a result of the malfunctioning of the antioxidant defense system. The occurrence of oxidative stress has been observed to result in detrimental effects on hepatocytes, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Figure 5 provides a concise overview of the pathophysiology of liver disease and the histology of hepatocellular carcinoma.

Fig. 5
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Outline of the pathophysiology of liver disease and histopathological progression of hepatocellular carcinoma. a Risk factors for hepatotoxicity can be classified into exogenous vs. endogenous factors. From mechanistic point of view risk factors can affect at different levels of events leading to liver injury. Initial injury exerted through direct cell stress, direct mitochondrial inhibition (β-oxidation) which cause mitochondrial dysfunction, ER stress, oxidative stress and increased level of ROS, all leading to hepatic inflammation. b Mitochondrial Permebility Transistion (MPT) leads to necrosis or apoptosis depending on the availability of ATP, Extensive ROS formation and steatohepatitis induces the release of inflammatory cytokines which caused apoptosis and necrosis of hepatocytes. c Necrotic hepatocytes send danger signals to neighbouring cells (HSCs and KCs) that induce the activation leading to fibrotic remodelling of extracellular matrix such as collagen synthesis and deposition to fibrosis. d Progressive and continuous cycles of this destruction—regenerative process culminates in cirrhosis. e Cirrhosis is characterized by abnormal liver nodule formation surrounded by collagen deposition and scaring. Subsequently, hyperplastic nodules followed by dysplastic nodules and ultimately hepatocellular carcinoma (HCC)

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Antioxidant activity effects

Studies have been carried out to establish the antioxidant activity of Desmodium species and were shown to possess a considerable scavenging activity using different models. D. gangeticum (shalparni in ayurvedic medicine) plant that demonstrate a potent DPPH scavenging activity (Govindarajan et al. 2003, 2006, 2007; Niranjan and Tewari 2008; Kurian et al. 2009; Rastogi et al. 2011). The higher antoxidant capacity were found in D. heterocarpon, D. microphyllum, D. sequax and D. uncinatum it is due to the presence of various specialized metabolites such as total polyphenols, total flavonoids and total flavonols (Tsai et al. 2011).

The hydro-alcoholic extract of D. adscendens leaves was shown to possess a considerable scavenging antioxidant activity. The results showed that the extract contains both flavanoid and polyphenolics components in significant levels and also a direct correlation between these phenolic compounds and antioxidant activity was also noted with 0.96 R2 value (Muanda et al. 2011).

The whole plant methanolic extract of D. triflorumwas subjected to fractionation using various solvents such as n-hexane, chloroform, ethyl acetate and n-butanol. All the extract were analysed for total phenolics, total flavonoids, scavenging activity of DDPH free radicals, antioxidant capacity and reducing power of the extract. The fingerprint analysis by HPLC fractions showed that the presence of higher vitexin content in n-butanol fraction. Various studies indicated that vitexin has several pharmacological properties including antioxidant (Fu et al. 2007). The evaluation of the antioxidant properties of leaf alcoholic extract of D. styracifoliumwas conducted using a photometric technique. The extract was used to find out scavenging potential for hydroxyl radical, superoxide radical, free radical of cigarette smoke, and peroxide radical. The inhibitory effect for these free radicals i.e. 60.7%, 87.5%, 21.1%, and 31.6%, respectively were found (Mao et al. 2007).

Abscess effects

An abscess refers to a distressing accumulation of pus, typically resulting from an infection caused by bacteria, viruses, or fungi. Both the Indian Traditional Medicine (ITM) and Chinese Traditional Medicine (CTM) systems employ the utilization of plant components that are subjected to squeezing and maceration processes for the purpose of treating abscesses that manifest either subcutaneously, internally within the body, within an organ, or in the interstitial spaces between organs. The application of a paste made from fresh roots and an extract derived from D. caudatum has been suggested for the treatment of cutaneous as well as deep lung and liver abscesses, as reported by the Editorial Committees of Guizhou Institute of Chinese Medicine (1970) and the Fujian Institution of Chinese Medicine (1994). According to Maheshwari (2019), the utilization of entire plants of Desmodium oldhamii Oliv. and D. triflorum as medicinal remedies for the treatment of abscesses resulting from pyogenic infections has been observed in the Kullu district of the North-West Himalaya. The aerial part (9 g) and root (15 g) of D. triquetrum are utilized in their entirety after being cooked to address lung abscesses and liver parasites, as documented by Gan (1967) and Libman et al. (2006).

Anti-analgesic and anti-nocieptive activity

Using animal models of acetic acid-induced writhing response and formalin test, the analgesic effect of D. triflorum DC methanolic extract was investigated. It was found that the extract and indomethacin at the assayed doses caused a significant (p < 0.001) inhibition on the writhing responses when compared to the control, which may be due to the inhibition of arachidonic acid metabolites’ synthesis. According to the enhanced reaction time (RT), all doses increased the threshold of heat tolerance; 200 mg/kg increased reaction by 3.8 s over the course of an hour (Lai et al. 2009). D. gangeticum aerial parts and roots were demonstrated to have analgesic properties through water decoction (Rathiet al. 2004). The considerable anti-nociceptive activity of the petroleum ether fraction (PEF) from the ethanol extracts of Desmodium podocarpum DC. (synonym of: Hylodesmum podocarpum (DC.) H. Ohashi & R.R. Mill) was demonstrated by the mice prolonged behaviour in the hot plate test (more than 120 s). When compared to the negative group of animals given distilled water, PEF significantly extended the mice’s latency duration (Zhu et al. 2011).

After using diclofenac sodium and ethanol extract of plant leaves as analgesics, mice’s writhing response to pain decreased significantly, from 66.7 to 16.5 per 20 min (p < 0.01). Desmodium pauciflorum (Nutt.) DC. (synonym of Hylodesmum pauciflorum (Nutt.) H. Ohashi & R.R. Mill) ethanolic leaf extract lowers writhing animals from 66.7 to 43.5, 29.5, and 44.2 (Hassan et al. 2013).

Aqueous leaves extracts of D. adscendens leads to a dose dependent decreases in pain sensitivity following the hot plate test compared with control with mean values for duration of paw flick low dose (LD) and high dose (HD) treated groups during the chronic phase were 8.9 ± 2.4, 13.03 ± 2.8, 18.77 ± 1.4 respectively. There was a significant increase (p < 0.01) in paw flick of HD treated group compared to the control (Charles et al. 2016). The anti-nocieptive effects of D. caudatum extract (DCE) at high dose was even more than that of ibuprofen 90 min after administering the drugs that exhibits a considerable prolonged latency period (55 ± 0.5 °C) of mice in the hot-plate test (Ma et al. 2011a, b).

Anti-inflammatory effects

Gangetin, a pterocarpan compound in D. gangeticum (Ghosh and Anandakumar 1983), inhibited 14% of carrageenan-induced oedema in rats’ hind paws but had little effect on cotton granuloma. D. gangeticum is a good source of traditional medicine that scavenges free radicals and indirectly treats inflammation. Rastogi et al. 2011 found that the final dosage decreases 61% of granuloma pouch inflammatory exudates in rats and 22% of formaldehyde-induced arthritis in albino rats. D. gangeticum methanolic extract was tested for antioxidants and lipid peroxidation in mitochondria and tissue homogenates of normal, ischemic, and ischemia-reperfused rats by Kurian et al. (2008).

According to Lai et al. (2009), Anti-inflammatory effect of methanolic extract of D. triflorum (MDT) was investigated and the test concentration of 0.5 and 1.0 g/kg body weight decreases the paw odema at 3rd 4th 5th and 6th hours after λ- carrageenan administration (Ilandara et al. 2015). At the third hour, the anti-inflammatory effect reached its maximum which was even equivalent to indomethacin (10 mg/kg). Furthermore, the edema paw showed a significant (p < 0.01) drop in the levels of nitric oxide, malondialdehyde, interleukin-1beta, and tumor necrosis factor (Lai et al. 2009). The total flavonoids isolated from aqueous extract of D. styracifolium showed notable anti-inflammatory activity in mice induced by croton oil at a dose of 50 mg (Gu et al. 1988).

At a dosage of 2000 µg/mL, the hexane fractions of D. velutinum and D. scorpiurus shown noteworthy (p < 0.05) anti-inflammatory properties of 76.9 and 68.6%, respectively. The effects of the reference drug, Diclofenac Sodium, which lowers inflammation by preventing prostaglandin synthesis through inhibition of cyclooxygenase in the arachidonic acid pathways (Della Loggia et al. 1986), were comparable to the activities of the extracts and fractions of D. velutinum and Desmodium scorpiurus (Sw.) Poir. (Skoutakis et al. 1988; Chen et al. 1995).

Gomes et al. (2012) found that D. adscendens procyanidins modulate the arahidonic acid pathway, inhibit gene transcription, express proteins, and secrete anti-inflammatory mediators. D. gyrans inhibits inflammatory responses by targeting NF-kB and reducing NO and PGE2 release in LPS-activated macrophage-like cells. The dose-dependent inhibition of NO production (48.39 μm) was up to 86% at 300–400 μg/mL. C. motorius (synonym for D. gyrans)ethonolic extract (Cm-EE) significantly reduced PGE2 generation (91.64 mg/mL) in LPS-treated cells by up to 90% at 100–300 μg/mL (Kim et al. 2014).

Anti-fibrotic effects

Whole plant of D. triquetrumis used for the treatment of lung, uterine muscles and liver fibroids (Tabuti et al. 2003). The alcohol-water extraction of  D. pulchellum was found to possess antifibrotic on experimental hepatic fibrosis induced by CCl4 in rat which shows serum glutamic pyruvic transaminase, hyaluronic acid, gamma globulin and Hyp content were significantly decreases (p < 0.001) when treated with alkaloid fraction (20 mg/Kg, 40 mg/Kg) similar to those of positive control group that received Colchicines (Ming et al. 2001).

Cytotoxic activity

The cytotoxic activity of several isolated compounds (Desmovelutin D, desmovelisoflavan A, 1-methoxyerythrabyssin II, gangetin, and desmodin) derived from D. velutinum was assessed against four human cancer cell lines (A549, HepG2, HuCCA-1, and MOLT-3). The results indicated a noteworthy cytotoxic effect on MOLT-3 cells, with IC50 values ranging from 3.4 to 27.9 µM (Kaweetripob et al. 2022). The stem of Desmodium blandum Meeuwen has been found to contain alkaloids and flavonoids, such as citrusinol (55) and (Z)-1-(3-hydroxy-2,4-dimethoxyphenyl)-3-(4-hydroxy-3-methoxyphenyl) propene (58). These compounds have demonstrated significant cytotoxic activity against KB cells, with IC50 values of 14.9 µg/mL and 15.1 µg/mL respectively. Additionally, they have shown cytotoxic activity against Hep G2 cells, with IC50 values of 15.7 µg/mL and 40.8 µg/mL respectively (Ning et al. 2009). In a study conducted by Rashid et al. (2013), it was observed that the methanol extract obtained from Desmodium paniculatum (L.) DC. exhibited notable cytotoxic effects on brine shrimp nauplii.

The LC50 value of this extract was determined to be 50.01 µg/mL, which was compared to a positive control (vincristine sulphate, 0.95 µg/mL) and a negative control (DMSO) that did not result in any mortality. According to Karim et al. (2021), the methanolic and ethanolic extracts of  D. triflorum exhibited a minimal level of toxicity, as indicated by their LC50 values of 34.50 µg/mL and 61.64 µg/mL, respectively. Additionally, the regression coefficients (R2) for the methanolic and ethanolic extracts were found to be 0.913 and 0.884, respectively. Bandekar et al. (2021) reported the identification of terpenoids derived from  D. oojeinensis, which exhibited a notable cytotoxic effect against lung cancer cell lines A-549. At a concentration of 80 µg/mL, these terpenoids demonstrated a growth inhibition rate of 81.5%. In comparison, the standard drug Adriamycin displayed a growth inhibition rate of less than 10 µg/mL. In their seminal study, Li et al. (2010) made the groundbreaking discovery that D. elegans contains three triterpenoids, namely lupenone (61), lupeol (62), and botulin (63). These chemical constituents have demonstrated promising anti-tumoral properties against various cancer cell lines, including U251-MG (Malignant Glioblastoma Tumour cell line), HCT116(Human Colorectal Carcinoma cell line), and A375 (Human Melanoma cell line). The mechanism of action involves the depolarization of the mitochondrial membrane potential (MMP) and the activation of apoptotic signaling pathways mediated by caspase 3/9, as elucidated by Jung et al. (2019).

Hepatoprotective activity

Studies were carried out to evaluate the hepatoprotective activity of the chloroform extract of roots of D. gangeticum against carbon tetrachloride (CCl4) induced liver damage in rats (Prasad et al. 2005). The valuation was done by measuring the increased serum levels of total proteins and decreased levels of bilirubin (total and direct), serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) in the group of rats pre-treated with the chloroform extract. The flavonoid and alkaloid fraction of D. gangeticum exhibits a potent inhibition of ferrous sulphate-induced lipid peroxidation in both liver and spleen (i.e. 0.68 ± 0.09 and 0.278 ± 0.02; 1.66 ± 0.18 and 0.381 ± 0.05 respectively) when compared it with the value of (p < 0.001) disease control.

Desmodium pulchellum, used to treat infectious hepatitis and hepato-splenomegaly, decreased CCl4-induced hepatic fibrosis in rats (Ming et al. 2001). D. uncinatum aerial part methanol extract showed concentration-dependent reduction of lipid peroxidation, with an IC50 of 43.6 µg/mL, lower than silymarin (112.2 µg/mL). Three primary fractions—ethyl acetate, n-butanol, and residual aqueous—were analysed from this crude extract. Tsafack et al. (2018) found that the n-butanol and EtOAc fractions had higher lipid peroxidation inhibitory activity than the crude extract due to their higher content of C-glycosylflavonoids and cerebrosides. The residual aqueous fraction was almost inactive (IC50: 370.6 µg/mL).

Desmodium triquetrum on hepatospecific enzymes, serum bilirubin, SOD, CAT and GSH in rats with CCl4 induced liver damage were significantly (p < 0.05) rise with CCl4 treated group as compare to normal and administration of ethanolic plant extract considerably reduce the increased levels of these liver enzymes i.e. SGOT-154.8 ± 15.32 IU/L, SGPT-117 ± 20.24 IU/L, SALP-112.5 ± 8.08 IU/L and serum bilirubin-0.4 ± 0.03 mg/dl and caused a subsequent recovery as compared to silymarin treated group (Jayaram and Srivastava 2016). For the treatment of icteric and chronic hepatitis, respectively, the whole plant of Desmodium fallax (9–15 g) and the crude root extract (9 g) of D. elegans were administered orally together with some white sugar (ZhonghuaBencao, 1996).

In hepatoprotective studies, ethanolic extract of plant D. oojeinense on paracetamol intoxicated rats significantly (p < 0.05) altered the biochemical parameters i.e. paracetamol treated group serum SGOT (410.72 ± 6056 IU/L), SGPT (401 ± 3.64 IU/L), ALP (277.4 ± 2.52 IU/L) and total bilirubin level (3.22 ± 0.11 mg/dl) were significantly elevated meanwhile, the group treated with alcoholic extract of plant shows significant dose-dependent decrease in liver enzyme (SGOT-149.19 ± 5.12 IU/L; SGPT-101.20 ± 3.84 IU/L; ALP-145.19 ± 4.76 IU/L; TB-0.97 ± 0.05 mg/dl) parameters when compared with control group and standard (silymarin) (Jayadevaiah et al. 2012).

Shivakumar et al. (2021) reported that the induced toxicity of paracetamol resulted in higher levels of blood marker enzymes, including ALT, AST, ALP, and BUN, as well as a decrease in total protein and albumin levels. Additionally, it resulted in a drop in GSH and liver total protein levels and an increase in relative liver weight. Intoxicated animals with paracetamol exhibited a considerable reduction in both catalase and GPx activity. The ALT, AST, ALP, and BUN levels had been brought back to normal by the pre-treatment with a methanol extract of D. gangeticum leaves at dose levels of 400 and 600 mg/kg, and the results were similar to those of a conventional medication (Silymarin 100 mg/kg).

Toxicology

Acute toxicity study revealed the non-toxic nature of aqueous extract of D. triflorum, show any sign and symptoms of toxicity and mortality up to 2000 mg/Kg dose after fourteen days of inhibition and study which indicates the extract found to be safe and toxic free upto the dose level and all animals survived at a dose of 2000 mg/Kg body weight, the LD50 of the extract will be > 2000 mg/Kg body weight (Bhosle 2013). Oral administration of a methanolic extract of the whole plant of D. triflorum at doses of 0.5, 1, 2.5, 5, and 10 g/Kg was performed on 10 mice for each dose. According to Lai et al. 2010 and Lai et al. 2009, the researchers determined that the LD50 of the extract was larger than 10 g/Kg when it was given as a single dosage.

The mice were given 4.2 g/Kg of petroleum ether fraction (PEF) from the ethanol extraction of D. podocarpum, no mortality was observed during the assessment period of seven days with minimum lethal dose of PEF is more than 4.2 g/Kg which is equivalent to approximately 500 times of clinical dose (Zhu et al. 2011). Wang et al. (1997) conducted a dose-dependent experiment whereby they found that a water extract obtained from 60 mg of whole plant/kg of D. microphyllum considerably (P < 0.05) reduced the acute toxicity and mice death induced by ET-1 and S6b.

The potential toxicity of D. adscendens was assessed to determine the acute toxicity and administrated intraperitoneally upto 100 mg/Kg, exhibited no neurological deficit and when 300 mg/Kg was administered, abdominal contraction were observed after the 25% of crude injection. Abdominal contractions were not the only impacts of the plant extract at 1000 mg/kg; it also decreased exploratory behaviour and spontaneous motor activity, both of which were reversed in six hours. After 24 h of administration, no deaths have been reported (Rastogi et al. 2011).

The acute toxicity test for the purified aqueous fraction from the alcoholic extract of the whole plant of D. gyrans (DGMAF) was investigated. Although the mice were orally administrated with a single dose 5 g/Kg b.wt of DGMAF that dissolved in distilled water, there is no indication of toxicity effect within the first six hours after the treatment period for 14 days. No sign of visual observation i.e. physical appearances, behavioural pattern, salvation, sleep and mortality also no significant changes were seen in haematological data such as haemoglobin concentration and total count of leukocytes. Since there was no toxicity observed, doses above 5 g/Kg b.wt is not considered for further assessment and has been assumed as its LD50 (Indu et al. 2021).

In a study conducted by Joshi and Parle (2007), oral administration of D. gangeticum extract (DGE) was performed on mice at various doses ranging from 50 to 2000 mg/Kg in order to evaluate its potential harmful effects. The results indicated that no instances of mortality were seen, even when administering the highest dose of 2000 mg/Kg. No mortality was seen following oral administration of DGE, even at the higher dose of 2000 mg/kg. Despite the fact that animals administered doses over 1000 mg/kg had a high incidence of loose and watery feces as an adverse reaction. As a result, in order to enhance efficacy in animals, it is necessary to administer lower doses. The compound DGE demonstrated no signs of toxicity in the Brine Shrimp Lethality test, a method used to assess the larvae’s ability to eliminate insects, inhibit cancer cells in vitro, and produce various pharmacological impacts (Jabbar et al. 2004). The fractions of D. gangeticum did not exhibit any mortality or grossly abnormal behaviour in the rats, nor did they cause any drop in body weight, indicating a lack of acute toxicity. Consequently, the utilization of the flavonoid fraction in medical applications is deemed to be safe. According to a study conducted by Ghosh and Anandakumar in 1983, investigations on the toxicity of “gangetin” demonstrated no immediate harmful effects at an oral dosage of 7 g/kg. The compound was considered safe based on its comparatively low effective dosages. The absence of any reported harmful effects throughout the extensive use of D. gangeticum in traditional medicine is consistent with the findings of Rastogi et al. (2011). According to Shivakumar et al. (2021), the investigation on the toxicity of D. gangeticum (DGL) methanolic leaf extract at doses of 450, 1800, and 3600 mg/Kg b.wt revealed no deleterious responses, alterations in behaviour, or fatalities throughout the duration of the trial, indicating its non-toxic nature.

The present study aimed to assess the acute toxicity of the ethanol extract derived from the plant species D. oojeinense. This assessment was conducted by administering the extract orally to rats, using a dose escalation strategy. Specifically, the doses administered were 1/10th of the maximal dose, ranging from 100 mg/Kg to 2000 mg/Kg. The animals were subjected to continuous observation at intervals of half an hour for duration of 4 h, followed by an additional observation after 24 h, in order to assess any changes in their behaviour, neurological status, and mortality rates (Jayadevaiah et al. 2012).

Conclusion and future prospective

The global popularity of herbal remedies is increasing, with a significant proportion of individuals suffering from liver illnesses opting to utilize ethanobotanical/ethanopharmacological medicines. Ancient classical literature and findings from ethanomedical research provide clear evidence that herbal medications have been widely utilized in the traditional Indian and Chinese systems of medicine for the purpose of treating liver problems. This review paper examines the scientific advantages of specific Desmodium species in relation to their mode of action for hepatoprotection. The extent to which the phytochemical and biological activities of various Desmodium species have been thoroughly examined remains limited, leaving ample room for further research in this area. A number of biomolecules have been extracted from this species, displaying potential hepatoprotective properties. However, comprehensive clinical trials of these isolated compounds in humans have not been extensively conducted. This lack of thorough investigation serves as a valuable resource for researchers in identifying intriguing species and their isolated compounds for subsequent molecular docking studies. Additionally, it serves as an impetus to broaden the scope of research on the Desmodium genus by incorporating a wider range of previously unexplored species. Furthermore, a comprehensive collection of literature on the phytochemistry of all existing Desomidum species exhibiting hepatoprotective action was provided. Additionally, there have been reported gaps in research pertaining to this genus.

The existing body of research indicates that the genus Desmodium possesses a wide range of cellular and molecular activities, making it a promising candidate for the development of alternative medicinal agents. However, further pharmacological studies, including investigations using animal models and exploration of phytochemical properties, are necessary to provide additional evidence supporting its hepatoprotective uses and to facilitate the development of effective drugs.