Phytochemical and ethno-pharmacological profile of Desmodium gangeticum (L.) DC.: A review

Desmodium gangeticum (L.) DC. is a well explored traditional Indian medicinal plant used to treat neurological imbalances. Recent pharmacological studies established its multi-directional therapeutic significance as anti-leishmanial, anti-inflammatory, cardio-protective drug. Moreover, it has detoxifying, blood purification property which might be attributed to its immunomodulatory activity. Phytochemical research revealed the plant is rich in alkaloids, pterocarpans, phospholipids, sterols and flavanoids. The review emphasizes primarily on folkloric uses, pharmacological activities of the extracts, biological activities of isolated compounds, toxicity and safety profile of Desmodium gangeticum to provide a comprehensive data for researchers to hit upon new chemical entity responsible for its claimed traditional uses and further clinical trials.


Introduction
Desmodium gangeticum (D. gangeticum) (L.) DC. (Family: Fabaceae) commonly known as Shalaparni is an important species of the genus Desmodium. Due to broad spectrum therapeutic potentiality, it is extensively practiced as traditional medicine in India and other parts of sub-continent over a long period of time 1 . D. gangeticum is a sub-tropical perennial herb grows in dry hill areas, mainly in the basement of Westernghat region and Himalayan territory. It is sweet in taste and mild warming in action 2 . Vedic literatures describe its potentiality as regulator of nervous (Vata), venous (Pitta) and arterial (Kapha) systems essential to restore health 3 . Traditionally, the roots are used as expectorant and in snake bite and scorpion sting 4 . It is an ingredient of Ayurvedic preparations like 'Dashmoolarishta' and 'Dashmoolakwaath' recommended for post-natal care to avoid secondary complications 5 . Moreover, pharmacological studies reveal the potentiality of D. gangeticum extract and its active principles viz. desmodin, hordenine and gangetin as anti-amnesic, immunomodulator, anti-diabetic, antioxidant, cardio-protective, hepatoprotective, anti-inflammatory drug 6 . An attempt has been taken to compile the upto date information regarding phytochemical and ethnopharmacological aspects of D. gangeticum.

Taxonomy and botanical description
The genus Desmodium is derived from Greek word 'Desmos' means 'bond' or 'chain' like due to the resemblance of the jointed seed pods to links of a chain. It is distributed mainly in tropical and subtropical regions of the world. Among 20-25 different species, D. gangeticum shows highest bio-diversity in India (Figure 1).
The taxonomical classification of D. gangeticum is as follows 7  D. gangeticum is a perennial erect or ascending shrub, grows upto 2 to 4 feet. The stem is angular, woody with numerous prostrate branches. Leaves are small (3-14 x 2-7 cm), ovate-oblong or rounded in shape, covered with numerous gray colour numerous trichomes; Flowers are small (4-7 cm), purple or white in color. Calyx are 4-5cm long, pubescent. Seeds are small, pale yellow, kidney-shaped. The lateral roots appear yellow with smooth texture. Its flowering-fruiting season is during the months of March to December 8 .

Traditional uses and Ethno-pharmacology
In Indian sub-continent, the shrub traditionally being used as antipyretic, diuretic, astringent (used in irritable bowel syndrome, diarrhoea and dysentery), anticatarrhal, diuretic, anthelmintic, laxative and nervine tonic where as in China D. gangeticum is used as folkloric medicine primarily to treat fever, neutralize toxins, inhibit pain, invigorate blood circulation, suppress cough and alleviate dyspnea 9 .
The roots of D. gangeticum (Local name: Kaganila akatono) chewed by the tribal people of Bulamogi community, Uganda to cure premature ejaculation 10 .
Pawara tribals of Satpuda Hills of Nandurbar district, Maharashtra, India combine the root powder of D. gangeticum (Local name: Salvan) with honey and applied frequently to treat mouth ulcer 11 .
Assamese people of Assam province in India, topically apply the paste of leaves of to cure the eczema infection along with other dermal disorders 13 .
10 gm of dried crushed roots and Pseudarthria is mixed together and boiled in 200 ml of water for 3 minute and 2 ml of water decoction is prescribed thrice daily after meal by tribal people of Waynad of Kerala, India, to treat type 2 diabetes mellitus 14 .
Root powder is boiled with milk and half cup of it is prescribed for seven or more days by tribal people of Jalgaon District, Maharastra, India, to promote flatulence 15 .
Whole plant is prescribed traditionally by Tribals of Jhalod Taluka of Dhahod district, Gujrat, India against several gynecological disorders and to prepare "Salampak" tonic 16 .
Villagers of Sivagangai district, Tamilnadu, India, drink leaf decoction (locally known as Pulladi) twice a day for 2 -3 days to cure diarrhea and dysentery. Leaf paste is applied on anus once a day for two weeks to cure piles 17 .
Chenchu tribal communities, Rudrakod of Nallamalai hill ranges of Andhra Pradesh, India, orally administer one spoonful root extract (locally known as Gitanaramu) twice a day, to cure whooping cough. Moreover, the leaves powder with a pinch of salt and applied on boils and blisters 18 .
Bheel and Bhilala tribes, Jhabua District Madhya Pradesh, India apply topically fresh leaves juice to treat scabies and ringworm 19 .
Chinese tribes administer root extract (9-15 gm/day) orally to treat diarrhea and given to children as sedative agent. Root and leaf pastes are applied externally to get relief from toothache and headache respectively 9 .
Water decoction of root and aerial parts of D. gangeticum is used as antipyretic, anti-inflammatory and antinociceptive phyto-medicine by various Indian tribes throughout India 20 .
Paliyar and Muthuvar Tribes, Theni District of Tamil Nadu, India, prescribe shade dried roots decoction (locally called Muvilai kurunthu) against asthma and other bronchial complications 21 .
Tribes like Gond, Kols, Mushar, Baiga & Nutts in Vindhya region of Uttar Pradesh, India, administered orally root paste and powder to treat typhoid fever, cerebrospinal meningitis and also as an antidote of snake venom 22 .
Different Indian tribes drink dried leaves powder decoction as health tonic 23 .

Antioxidant activity
Chloroform root extract of D. gangeticum (2-1000 μg/ml) were tested in-vitro to establish the antioxidant potential against ischemia reperfusion injury model in isolated rat heart. The IC 50  Further, two novel compounds viz. caffeic acids and chlorogenic acid were isolated from flavanoid fraction and their antioxidant activity was tested in-vitro under arthritic conditions. The results supported strong antioxidant activity, which might be associated with the anti-arthritic activity of the plant as most of the anti-arthritic drugs act by reducing the oxidant damage at sites of inflammation 31 .
In-vivo free radical scavenging potential of aqueous extract of D. gangeticum root was accessed by inducing oxidative stress in ischemic reperfused rat heart model. The observations supported antioxidant capacity of D. gangeticum as compared to standard drug verapamil against revascularization injury 32 .
Hydro-alcoholic extract of D. gangeticum strongly scavenged DPPH radical (IC 50 2.01 mg/ml) and NO (IC 50 14.79 mg/ml) in dose dependent manner. was found to have activity. The total antioxidant capacity of the extract was found to be 149.91 % as compared to standard ascorbic acid 87.8 %. The extract also inhibited the ferrylbipyridyl (chromogen) formation in a dose dependent fashion (IC 50 0.115 mg/ml) 33 . Juice of whole plant of D. gangeticum posses anti-rheumatic and anti-osteo arthritic activity via anti-inflammatory activity. The activity might be associated with several phytoconstituents like polyphenolics, pterocarpinoid (gangetin) 35 .

Anti-inflammatory and anti-nociceptive activity
Gangetin, a pterocarpens, isolated from n-hexane extract of root of D. gangeticum showed significant antiinflammatory activity in both exudative and proliferative phases of inflammation in rat model at dose of 50 and 100 mg/kg body weight 36 .

Anti-leishmanial and immunomodulatory activities
Glyco-lipids viz. Aminoglucosyl glycerolipid and glycosphingolipid, isolated from the roots of D. gangeticum showed potent antileishmanial and immunomodulatory activities in-vitro by enhancing nitric oxide (NO) production and provided resistance against infection established in peritoneal macrophages by the protozoan parasite Leishmania donovani 37 .

Cardio-protective activity
Methanolic extract of D. gangeticum roots preserve mitochondrial respiratory enzymes and thereby protecting rat heart against oxidative stress induced by reperfusion injury at a dose of 50, 100 mg/kg body weight 39 .
Further, chloroform root extract (100 mg/kg) mediates cardio protection in ischemic reperfusion injury model in isolated frog heart through negative ionotropic and chronotropic. The effect was mediated by stimulating the G coupled receptors similar to the action of acetylcholine. Both the studies were compared with verapamil (0.2 mg/kg body weight, i.p.), standard cardioprotective drug 40 .
Pre-treatment of the aqueous extract of D. gangeticum (3 ml/100 g) for thirty days showed reduced cholesterol level and free radical scavenging potential in-vitro against isoproterenol induced myocardial infracted rats. These findings were associated with cardio-protective activity of the plant 41 .
Ethyl acetate extract of D. gangeticum root (100 mg/kg) showed potent cardio-protection against ischemia reperfusion-induced oxidative stress models. The extract reduced TBARS in myocardium along with enhanced the recovery of antioxidant enzymes from the assault of ischemia reperfusion injury. The effects of the extract might be related to the inhibition of lipid peroxidation 42 .
Methanol extract of D. gangeticum root (80 µg/ml) showed myocardial protection in rat ischemia reperfusion injury model by stimulating muscarinic receptors. The activity might be due to the reduction of calcium overload and free radical release and improved recovery of antioxidant enzyme towards myocardium 43 .
Oral administration of root ethanolic extract of D. gangeticum significantly decreased the ulcer index and lesion number in a dose dependent manner against ethanol induced acute gastric ulcer in mice. The highest dose (150 mg/kg) of the extract provoked a marked increase in protein and glutathione levels, when compare to control. Furthermore, gastric juice, free acidity and total acid output were inhibited in a dose-dependent manner at p<0.05 level 45 .

CNS activity
Aqueous extract of D. gangeticum showed potent anti-writhing activity in the acetic acid-induced abdominal writhing assay. It also exhibited moderate CNS depressant activity in-vivo. The effects of extract on locomotion were compared with standard CNS drugs 46 .
Pretreatment with aqueous extract of D. gangeticum (100, 200 mg/kg, p.o.) for seven successive days, reversed scopolamine induced amnesia in mice. Study revealed that the plant increased mice brain acetylcholine content and decreased acetyl cholinesterase activity in a similar fashion to the standard cerebro-protective drug piracetam. Hence, aqueous extract of D. gangeticum can be used to delay the onset and reduce the severity of the symptoms of dementia and Alzheimer's disease 48 .

Antidiabetic activity
Methanolic extract of aerial parts of D. gangeticum (100 and 250 mg/kg) for 3 weeks showed a significant antidiabetic activity in rats by stimulating insulin secretion from MIN6 and pseudoislets cells of pancreatic islet.
It plays a major role to maintain the lipid profile of the rats by reducing cholesterol and triglycerides level and increase in high density lipoproteins (HDL) significantly (p < 0.05). This supports the traditional use of D. gangeticum as anti-diabetic drug 49 .

Hepatoprotective activity
Hepatoprotective activity of the chloroform extract of roots of D. gangeticum was evaluated in-vivo against CCl 4 induced liver damage in rat models. The study revealed extract caused an increase in serum levels of total proteins and decrease levels of bilirubin, serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) in pretreated groups 50 .

Renal protective activity
Oral administration of ethanolic extract of whole plant of D. gangeticum (100, 200, 400 mg/kg) for 30 days showed marked renal protective activity in-vitro against streptozotocin induced diabetic rats. The study was compared with glibenclamide (600 μg/kg), standard anti-diabetic drug 51 .

Wound healing activity
Topical application (10% w/w ointment of aqueous extract of D. gangeticum) showed marked wound healing potential in-vivo in Wistar rat models. Results indicated a decrease in wound closure time and increment in wound contraction. Moreover, a significant increase in proline content was also observed. All the studies were compared with standard povidone iodine ointment 52 .

Safety profile
Toxicity of D. gangeticum extract was accessed in mice at different doses (50-2000 mg) and parameters like hyperactivity, grooming, convulsions, sedation, hypothermia and mortality were observed. No mortality was observed following oral administration of highest dose (2000 mg/kg) of extract. However, doses more than 1000 mg/kg produced profuse watery stools, ptosis (dropping of upper eyelids) and lethargy in animals. Further, studies conducted on gangetin showed no acute toxicity up to 7 g/kg orally which made it quite safe. Further, as traditional medicine no reports of toxicity of D. gangeticum have been documented 53 .

Discussion
For ages, D. gangeticum has been used for the treatment of various ailments in traditional and folklore medicine throughout India, China and other African countries. D. gangeticum is one of the main ingredients of several Ayurvedic formulations like Dashamularishta, Cyavanaprasam and Agasthyarasayanam, routinely prescribed to treat colic pain, fever, respiratory diseases 54 . The decoction of Dasamula and Laghu pancamula, polyherbal formulations are used in pain, hysteria, rheumatism, asthma, cardiac and renal problems 55 . Isolated phytoconstituents like Gangetin, Desmodin, 5-Methoxy-N,Ndimethyltryptamine are considered as predominant bioactive constituents due to their diverse therapeutic potentiality 56 . Although the constituents responsible for the pharmacological properties of the plant seem to have been determined, the molecular mechanisms of most of these principles are still unknown. The bioassay guided isolation, identification of the bioactive components is essential and in depth research is also crucial to reveal the structure-activity relationship of these active compounds. Based on these facts, the authors made an upto date information highlighting the current ethnopharmacological and phytochemical status of the plant.