INTRODUCTION:

Cissus quadrangularis L, belongs to family Vitaceae, is a common succulent perennial climber, characterized by a thick quadrangular fleshy stem, an edible plant which is distributed throughout India particularly in tropical regions¹. This plant is commonly known as bone setter due to its ability to join the bones. This plant is called by various other names in different parts of the country like

Vajravalli in Sanskrit, Hadjod in Hindi, Kandvel in Marathi, Hadbhanga in Oria, Vedhari in Gujrati, Perandai in Tamil, Nalleru in Telugu and Veldgrap in Indian languages and Edible-stemmed vine in English. It is also known as Vitis quadrangularis².

Description of the plant

C. quadrangularis is herb, reaching a height of 1.5m. It requires warm tropical climate and propagated by stem cutting in month of June-July³. Stem is quadrangular, with internodes 8-10 cm long and 1.2 to 1.5 cm wide⁴. The surface is fibrous, smooth, glabrous, buff coloured with greenish tinge, dichotomously branched, angular portion reddish-brown, no taste and odour⁵.

Tendrils are simple, opposite to the leaves, leafless when old. Leaves are simple 2.5-5cm long, broadly ovate or reniform, sometimes 3-7 lobed, denticulate, glabrous, cordate, rounded, truncate or cuneate at the base; petioles 6-12mm long, stipules small broadly ovate, obtuse. The leaf portion constitutes only 5-8% of the aerial plants parts; the fleshy, green stem is the major portion⁶. Flowers are in shortly peduncle cymes with spreading umbellate branches, small greenish white, bisexual, tetramerous, opposite to the leaves. Calyx is cup shaped, truncate or very obscurely lobed. Petals are 4, ovate-oblong, short, stout. Fruit is obovoid or globose, succulent, scarcely 6mm, long apiculate, red when ripe, 1-(very rarely 2) seeded; seeds are ellipsoid or pyriform^3,5.

Phytochemistry:

There are various chemical constituents isolated from the Plant

Bitter alkaloid: Quinine⁷

Benzopyrone: Coumarin⁷

diterpenes: Phytol⁸

Elements : Calcium, Iron, Zinc, Manganese, Chromium, Magnesium, Copper, Cadmium, Phosphorus, Selenium^9,5,10

Essential fatty acid: omega-3, Linoleic acid¹¹

Glycosides: Cardiac glycosides¹²

Iridoid 6-O-trans-cinnamoyl catapol¹³

Isoprenoid: Squalene¹⁴

Methylxanthine: Caffeine⁸

Phenylpropene: eugenol¹⁴

Polyphenols: Quercetin, Kaempferol, Leuteotin, Lupeol, Daidezein, Genistein¹⁵

Phytosterol: Stigmasterol¹⁶,β-sitosterol, daucosterol, α- amyrins and α-amyrone, tarexerol¹⁷

Phytoestrogen: Friedelin¹⁸

Saturated fatty acid: Stearic acid¹⁴

Simple alcohol: nonanol¹¹

Steroids: Ketosteroids, Oxosteroids¹⁹

Stilbene derivatives: Quadrangularins A, B and C, resveratrol, piceatannol, pallidol, perthenocissin, α- and β amyrins and α-amyrone³

Tannins: Catechic²⁰

Unsaturated fatty acid: Oleic acid¹⁴

Vitamins: A,C and E²¹

Volatile fragrance oil: Asarone¹¹

Some pharmacological active species of Cissus quadrangularis

There are approximately 350 species in genus Cissus from which, more than a dozen is used in different countries as a folk medicine to treat various ailments²² They are:

a. In Cameroon, Species C. araloides is used as antimicrobial and toxological agent against microorganism of gastrointestinal and urinal tracts while species C. debilis has been investigated for antiproliferative activity on human Caco-2 cells²³

b. Species C. assamica is used as antivenome in Bhutan, China, India Cambodia, Nepal and Thailand²⁴

c. C. hamaderohensis showed inhibition of angiotensin converting enzyme (ACE), neutral endopeptidase (NGP) and aminopeptidase N (APN) in West Asia²⁵.

d. C. hypoglauca is used as treatment of sore throat by Bush medicine practitioners in Australia²⁶

e. In Nigeria C. ibuensis is used as treatment of gastrointestinal disorders rheumatism and arthritis²⁷ while studies on C. populena showed that it has anti-sickling and anti-bacterial properties^28,29. It is also used to treat trypanosomiasis³⁰. Methanolic extracts of C. populena increased proliferation of sertoli cells TM4 in in-vitro studies, but not in humans treated for 72 days³¹ .

f. In Africa and Asia C. rotundifolia has been studied for its antidiabetic³² and anti-parasitic activities³³.

g. C. rubiginosa is used for the treatment of dysentry and diarrhoea in Congo³⁴.

h. In Brazil C. sycoides is used as vegetal insulin as antidiabetic agent as well as diuretic, anti inflammatory, anticonvulsant and anxiolyte agent³⁵

i. In Trinidad and Tobago C. verticillata is used for the treatment of diabetes and urinary problems³⁶.

Ethnopharmacological uses

The whole plant is considered to be edible; while each part of the plant pharmacologically contributes to some activity. The efficacy against different activities varies for different extract³⁷.In Indian traditional medicine C. quadrangularis is used as a component of a plaster for treating swelling and bone fractures³⁸. The roots and stems are most useful for healing of fracture of the bones. The stem is bitter, it is given internally and applied topically in broken bones, used in complaints of the back and spine. Leaves and young shoots are powerful alternatives, dried and powdered; they are administered in certain bowel infections connected with indigestion, otorrhoea and epistaxis³⁹. Decoction of shoots with dry ginger and black pepper is given for body pain the infusion of plant is anthelminitic. The herb is fed to cattle to induce flow of milk. The ash of plant is useful substitute for baking powder⁴⁰. The plant has been documented in Ayurveda for the treatment of osteoarthritis, rheumatoid arthritis and osteoporosis^41,42. The use of sap with tamarind has been reported in East Africa for the treatment of gonorrhoea⁴³. A paste of stem is given in asthma, burns and wounds, bites of poisonous insects and for saddle sores of horses and camels. A paste of the stem is used by traditional healers, applied as a poultice over bone fractures and swellings⁴⁴.

Pharmacological property

Bone healing activity

Paste of alcoholic extract of the plant has been reported to be used locally as well as intramuscularly facilitates rapid healing of fracture in albino rats⁴⁵. Ethanol extract (95%) enhances the development of cortical bone and trabeculae in fatal femur, which may be related to rich content of calcium, phosphorus and phytoestrogenic steroids and shown to influence early regeneration and quick mineralization of bone fracture healing process⁴⁶. Ethanol extract (95%) of whole plant possess anti-osteoporotic activity in ovariectomized rat model of osteoporosis at two different dose levels of 500 and 750 mg per kg body weight[38]. It has been reported that C. quadrangularis acts by stimulation of metabolism and increases uptake of the minerals calcium, sulphur and strontium by the osteoblasts in fracture healing^47,48.

Another study was conducted to investigate the effect of methanolic extract of C. quadrangularis (MECQ) on the healing process of experimentally fractured radius ulna of dog. Animals treated with methanolic extract of C. quadrangularis (50mg/kg s.c.) exhibited faster initiation of healing process as compared to the control group on radiological and histopathological examinations. There was also a decrease in serum calcium level to a greater extent in treated group than the control group. Healing was almost complete on 21^st day of fracture in the MECQ treated group and remained incomplete in the control animals but there was no significant alteration in serum calcium level in both groups on 21^st day of fracture⁴⁹.

The plant’s mechanism of action is found in the presence of 3-ketosteroids, which are anabolic and impart anti-glucocorticoid properties to tissues. These constituents are able to help heal and protect muscles, tendons and bones through their interaction with cortisol and other hormones and substances found in the body. These substances contribute to tissue breakdown by acting as “cleansers” in times of physical trauma or weakness, allowing dead proteins and other waste to exit the area. Active components of C. quadrangularis prevent the over activity of these substances, and help restore tissue to their normal state⁵⁰.

Antioxidant and free radical scavenging activity

Methanolic extract of C. quadrangularis was evaluated against free radical damage. The extract expressed significant inhibition in DPPH free radical formation, superoxide radical production and lipid-peroxide production in erythrocytes. Liver marker enzymes and antioxidant defence enzymes in rat liver homogenate were assessed in control and experimental animals. Carbon tetrachloride (CCl4) caused a significant increased level in aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), alkaline phosphate (ALP), and decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx) and reduced glutathione (GSH). By pre-treatment with extract of C. quadrangularis enzymes levels were reverted. The observations suggested that CQE exhibited inhibition of lipid peroxidation, free radical production and increase in antioxidant enzymes which confirms its antioxidant potential³⁷.

A study was carried out to evaluate the antioxidant activity of flavanoid rich fraction from C. quadrangularis on sodium perchlorate induced oxidative stress in rats. Animals were divided into four groups of six animals each. Male albino rats were fed with 0.2% sodium perchlorate to induce oxidative stress. The flavanoid rich fraction of the plant (1mg/100gm, 2mg/100gm) was administered orally along with sodium perchlorate to two groups of animals for 30 days. Animals showed increased antioxidant levels in serum, heart, liver, kidney compared with sodium perchlorate treated group. The results of this study suggested that flavanoid rich fraction of C. quadrangularis has potent antioxidant property⁵¹.

In another study extracts of C. quadrangularis were studied for antioxidant activity β- carotene linoleic acid model and by 1,1-diphenyl-2-picrylhydrazyl model. The ethyl acetate fraction of both fresh and dry stem extracts at a concentration of 100 ppm showed 64.8% antioxidant activity in the β-carotene linoleic acid system and 61.6% in the 1,1-diphenyl-2-picrylhydrazyl system. This fraction gave positive result for the presence of sterols, vitamin C and tannins as phytoconstituents. The antioxidant activity of methanol extract and aqueous extract were comparatively less significant than that of ethyl acetate extract and n-hexane extract showed the less activity⁶.

An in-vitro antioxidant studies were carried out on the chloroform and ethanol extracts of the C. quadrangularis using various free radical models such as DPPH, Reducing power assay, nitric oxide peroxide, superoxide scavenging and ABTS. In-vitro cytotoxic assay such as trypan blue dye exclusion and MTT assay were carried out both ethanol and chloroform extract against EAC cell line. The result exhibited that the ethanolic extracts have significant antioxidant potential than chloroform extract⁷.

Gastroprotective and antiulcer activity

Antiulcer activities of the ethanol extract of C. quadrangularis roots on indomethacin and ethanol induced gastric ulcer have been reported. The results obtained showed that the ulceration in gastric linings of the stomach of rats pre-treated with the C. quadrangularis extract before induction with ethanol and indomethacin decreased significantly when compared to the control. The protective effect of extract increased in dose- dependent manner in both ulcer models. There were significant decrease (p<0.05) in the number of ulcer lesions when rats were administered with the graded doses of the extract and ranitidine (100mg/kg body weights) compared with the control groups in both models. Results from this study suggested that the extract of C. quadrangularis roots possesses antiulcer activities⁵².

Another study showed antiulcer activity of methanol extract in experimentally induced ulcer in rat model by decreasing secretions and by enhancing glycoprotein levels. Methanol extract produced healing effect on aspirin induced gastric mucosal damage in rats through its antioxidative mechanism⁵³. Triterpenoids and beta-sitosterol present in methanol extract possessed anti-lipid peroxidating effect and thus preventing gastric damage⁵⁴.

Intake of aspirin increase lipid peroxidation status, xanthine oxidase, myeloperoxidase and decrease in selenium glutathione peroxidise activities in the gastric mucosa which resulted in mucosal damage at both cellular and subcellular level. Pretreatment with different doses of ethanol extract of C. quadrangularis (CQE) (250, 500 and 700mg/kg b.w.) for 7 days showed ulcer protection by 40, 71.2 and 72.6% respectively as compared to ranitidine (30mg/kg b.w.) by 71.9% in the aspirin rat model. This gastroprotective activity of CQE could be through its antioxidant effect and by the attenuation of the oxidative mechanism and neutrophil infiltration⁵⁵.

A study was conducted to investigate in-vitro H⁺-K⁺ATPase inhibitory potential of methanolic extract of C. quadrangularis in which total phenolic and flavanoid contents from extract was quantified and H⁺-K⁺ATPase inhibition assay was conducted in presence of standard (omeprazole) and methanol extract. Extract showed significant (*P < 0.05) proton pump in the gastric mucosal homogenate which was comparable to standard and is a potent inhibitor of proton pump⁵⁶.

Analgesic, anti-inflammatory and antipyretic activity

In a study the analgesic, effect of the drug as observed by Haffner’s tail flip and Eddy’s hot plate methods were dose related. There was increase in reaction time even with such small dose as 1/40^th of the LD₅₀. The effect lasted for about 4 hrs. C. quadrangularis exhibited significant analgesic activity compared to that of Aspirin when tested using Haffner’s clip and Eddy’s hot plate methods. The extract was found to be effective by both oral and i.p routes significantly (p<0.001) and reaction time was found to be increased by both methods. The duration of analgesic activity was from 2 to 4 hr and optimum effect was observed at 1/20^th-1/10^th of LD₅₀ dose. The extract compared well with acetylsalicylic acid^38,57.

In another study ethanol extract of C. quadrangularis had showed significant reduction in edema induced by carrageenan within 1to5 hrs. For the analgesic property, acetic acid induced writhing was significantly reduced in formalin test; the extract significantly decreased the painful stimulus in both phases of test which confirms its central and peripheral effect. Extract also reduced fever at high doses within 2 hrs on yeast induced hyperthermia in rats, which supported antipyretic activity of the plant⁵⁸.

The analgesic effect of the plant when used in bone fractures may be of great value in relief of pain³⁷.

Cox Inhibition

In an experiment acetone fraction of C. quadrangularis (AFCQ) inhibited cycloxygenase (COX-1), cycloxygenase (COX-2) and 5 lipoxygenase (5-LOX) enzyme activity. Almost all diseases are characterized by the inflammation and pain in response of different disorders like infection, injuries etc. Inflammation and pain indicate the presence of COX and 5 LOX. AFCQ extract exhibited COX and 5LOX inhibition with IC50 values of 7microgm/ml, 0.4 µg/ml and 20 µg/ml for COX 1, COX 2 and 5 LOX respectively. The extract not only showed anti inflammatory activity on RAW 264.7 cell line with IC₅₀ value 65 µg/ml but extract also inhibited proinflammatory mediators like iNOS and TNF alfa along with translocation of Nrf-2 and upregulation of HO-1⁵⁹.

Antimicrobial activity

Antimicrobial activity of ethanol, diethyl ether and aqueous leaf extract of C. quadrangularis against bacterial pathogens such as E. coli, K. pneumonia, S. aureus and fungal pathogens such as A. flavus, C. albicans, F. solani by in vitro agar well diffusion assay have been evaluated. The ethanol extract of the plant was found to posses strong antimicrobial activity against tested pathogens⁶⁰.

Methanol extract (90%) and dichloromethane of stems have been reported to possess antibacterial activity against S. aureus, E. coli, and P. aeruginosa and mutagenicity against Salmonella microsome⁶¹. Antimicrobial activity has also been reported from stem and root extract⁶⁶. The alcohol extract of aerial part was found to possess antiprotozoal activity against Entamoeba histolytica⁶². Alcoholic extract of the stem has been reported to posses activity against E.coli⁴⁶.

Antihypergyceamic activity

A study was performed to explore the antihyperglycaemic activity of ethanol extract of leaves of C. quadrangularis against alloxan induced diabetic rats. Ethanol extract (EtCQ) of C. quadrangularis and glyburide were administered orally in alloxan induced diabetic rats. In the acute study, the serum glucose level was estimated at 0,2,4,6 and 24 h after drug administration. The subacute study involved repeated administration of the drugs for 28 days, a serum glucose level estimated at 7, 14, 21 and 28 days. In the OGTT, D-glucose (2.5g/kg) was administered in diabetic rats half an hour after pre-treatment with EtCQ and glyburide. Serum glucose levels were estimated 30 min prior to glucose administration and at 0, 30, 60 and 120 min after glucose loading. In subacute study, repeated administration (once a day for 28 days) of glyburide and EtCQ caused significant reduction in the serum glucose level as compared to the vehicle treated group. EtCQ (400mg/kg) treatment prevented a decrease in the body weight of the diabetic rats. In the OGTT, EtCQ (200and400mg/kg) increased the glucose threshold at 30 min after the administration of glucose. The EtCQ (400mg/kg) showed significant antihyperglycaemic activity than EtCQ (100 and 200mg/kg), which concluded that ethanol extract of C. quadrangularis has antihyperglycaemic activity⁶³.

An another experiment was conducted to investigate the protective role of petroleum ether extract of C. quadrangularis (PECQ) on diabetes induced delayed fetal skeletal ossification.

In maternal diabetes delayed fetal skeletal ossification is one of the known complications. For this purpose before mating, female wistar rats were made diabetic with streptozotocin (STZ, 40mg/kg i.p.). After confirmation of pregnancy, the pregnant rats were divided into three groups, normal control group, diabetic control group and diabetic CQ group. The diabetic CQ group pregnant rats were administered PECQ (500 mg/kg b.w.) throughout their gestation period. Immediately after delivery, pups were collected from all experimental groups to conduct alizarin red S-alacian blue staining, to determine the pattern of skeletal ossification. Observation exhibited that there were fewer ossification centres and decreased extent of ossification of forelimb and hindlimb bones in the neonatal pups of diabetic control group as compared to those in the normal control group. Pretreatment with PECQ, significantly restored the ossification centres and improved the extent of ossification of forelimb and hindlimb bones in the neonatal pups of diabetic CQ group as compared to the diabetic control group. The study confirmed that PECQ treatment was helpful against diabetes induced delayed fetal ossification⁶⁴.

The hydroalcoholic extract of C. quadrangularis at dose level of 200 mg/kg b.w. exhibited promising anti-diabetic effect in the alloxan induced models in rats. However the overall anti-diabetic activity of the extract was found to be much less than standard drug Glibenclamide. The diabetic action may be due to suppression of transfer of glucose from the stomach to the small intestine and inhibition of glucose transport across the brush border of the small intestine⁹.

Antiarthritic activity

A study was conducted to evaluate the antiarthritic activity of active fraction of C. quadrangularis (AFCQ) extract of C. quadrangularis by employing CFA (complete Freunds Adjuvant) induced arthritis model in Wistar rats as in-vivo experimental model. Results obtained revealed that AFCQ at the dose of 100mg/kg b.w. was found to be more efficient in inhibiting rat paw edema as comparable to standard drugs celecoxib and methotrexate. This indicated that AFCQ having a significant anti arthritic activity against CFA induced arthritis⁵⁹.

Anti-osteoporosis activity

Ethanol extract was evaluated for its antiosteoprotic activity in ovariectomized rat model of osteoporosis at two different dose levels of 500 and 750 mg/kg per day. The rats were divided into five groups. First group served as control. All the remaining groups were ovariectomized control. Group 2 was fed with saline and served as ovarectomized control. Group 3-5 were orally treated with Raloxifen (5.4mg/kg) and ethanol extract of C. quadrangularis (500 and 750mg/kg), respectively. The biomechanical, biochemical and histopathological parameters showed that ethanol had a significant antiosteoporotic effect³⁸.

Central nervous system depressant and anxiolytic activity

The aqueous extract of C. quadrangularis exhibited GABA benzodiazepine receptor binding activity and its CNS depressant effect was studied. The different activities were tested for locomotor activity, effect on muscle coordination, antiaggressive and antianxiety activities. The results obtained indicated that aqueous extract of the stem (150 mg/kg, p.o) reduced locomotor activity, produced muscle relaxation and showed antiaggressive and antianxiety activities⁶⁵.

Anticonvulsant and sedative properties

To study anticonvulsant and sedative activities various animal models of epilepsy (maximal electroshock, n-methyl-d-aspartate, pentylenetetrazol, isonicotinic hydrazid acid and strychnine induced convulsions or turning behaviour) and insomnia (diazepam/kg b.w. induced sleep) were used. The study showed that the aqueous extract of the stem of C. quadrangularis strongly increased the total sleep time induced by diazepam (50mg/kg i.p.). It also protected mice against maximal electroshock, pentylenetetrazol, strychnine and methyl-d-aspartate induced seizures or turning behaviour and delayed the onset of seizures induced by isonicotinic hydrazid acid. The study confirmed the anticonvulsant and sedative properties of C. quadrangularis in mice⁶⁶.

Methanolic root extract of C. quadrangularis significantly inhibited acetic acid-induced writhings and increased tail flick withdrawl response in mice. The effect of extract on CNS were analysed by using spontaneous motor activity, exploratory behaviour, rota-rod performance and potentiation of pentobarbitone sleeping time in mice. The extract (50,100 and 200mg/kg i.p.) produced reduction in spontaneous motor activity, exploratory behaviour and motor coordination and prolonged pentobarbitone sleeping time. The findings suggested that methanolic root extract of C. quadrangularis contains some active constituents which may be sedative in nature⁶⁷.

Effect on biochemical parameter

A study was conducted to investigate the effect of C. quadrangularis on glycogen content in fresh water fish, Oreochromis mossambicus at 7 and 14 days. When compared with control fish, there was slightly increased in the glycogen content in the liver, gill and muscle tissue of fish treated with C. quadrangularis. The study concluded that for the growth and development of fishes C. quadrangularis is a beneficial source⁶⁸.

Antilipidemic activity

Ethanol extract of C. quadrangularis was orally administered to high fat fed rats (ghee+ normal feed in the ratio 2:1) at a dose of 583 mg/kg b.w. for 30 days. Animals were sacrificed at the end of the experiment. Biochemical analysis of serum was conducted for cholesterol, phospholipids, HDL and TG. Analysis results showed that the increased level of cholesterol, phospholipids, and TG were near about normal in groups treated with plant extract, there was significant reduction in cholesterol , phospholipids, and TG although HDL level was found to be significantly increased. The histopathological examination of liver and heart showed positive result. The results of biochemical observations and histopathological examination of rat’s heart and liver section, concluded that C. quadrangularis has significant antihyperlipidemic activity⁶⁹.

Antiobesity activity

The aqueous extract of C. quadrangularis stems and leaves contains flavanoids and stilbenes, which inhibit enzymes lipase, amylase and α-glucosidase and support the antiobesity of plant. In study lipase and amylase were much more susceptible for inhibition by components of C. quadrangularis as compared to α-glucosidase. Inhibition of such enzymes by C. quadrangularis claimed that this plant may be used as drugs to treat obesity and diabetes type 2⁷⁰.

Wound healing activity

Various extracts of C. quadrangularis (petroleum ether, chloroform and methanol) were evaluated for their wound healing activity on excision and incision models in albino rats. The results of study showed that all three extracts exhibited significant increase in wound contraction and formation of scar in incision wound model and there were significant increase in the breaking strength of resutured incision wound models treated by these extracts, as compared to control group (p<0.001). The result of study also indicated that although all three extracts of C. quadrangularis were possessing significant wound healing property but methanol extract had more significant wound healing property than the petroleum ether and chloroform extract in incision and excision wound models. The presence of phytosteols, triterpenes, glycosides phenols flavanoids, saponin, tannins, coumarin, ascorbic acid and quercetin in the plant may be responsible for wound healing activity. This study supports the popular use of plant to open wound in folk medicine⁷¹.

Anthelmintic activity

Methanolic and aqueous extracts of C. quadrangularis were investigated for in-vitro anthelmintic activity on earthworm Pheretima posthuma (Annelida). Extracts showed anthelmintic activity in dose dependent manner giving shortest time of paralysis (P) and death (D) with 100mg/ml concentration.The methanolic extract caused paralysis in 14 minutes and death in 40.55 minutes while aqueous extract showed paralysis in 15.67 and death in 40.67 minutes respectively against the earthworm Pheretima posthuma. The results of reference drug piperazine citrate for paralysis and death was 18.83 and 60.33 minutes respectively. Phytochemical analysis showed that tannins was present in extracts, and it may be possible that tannins were responsible for anthelmintic activity, as tannins can bind to free protein in the gastrointestinal tract of host animal or glycoprotein on the cuticle of the parasite and may cause death⁷².

Anti nociceptive activity

The chloroform and distilled water (20:80) extract of C. quadrangularis was evaluated for centrally acting and peripherally acting analgesic property on albino mice by using hot plate method, formalin test and acetic acid induced writhing method. The animals were treated with doses 250mg/kg i.p. and 350mg/kg i.p. Although both administered doses exhibited significant analgesic activity in animals but the animals those administered a dose of 350mg/kg b.w. had showed the maximum analgesic activity, which was comparable to standard drug⁷³.

Immunomodulatory effect

A study was conducted to investigate the effect of ascorbic acid, the major bioactive component from C. quadrangularis (CAA) extract on inflammatory cytokines and growth factors in non-steroidal anti-inflammatory drug (NSAID) induced gastric ulcer. Analysis of serum cytokines profile using enzyme linked immunosorbent assay (ELISA) exhibited an increase in interleukin (IL-1β, IL )-6, tumour necrosis factor alpha (TNF)-α, interferon)-gamma (IFN- γ) and decrease in IL-10, IL-4 and prostaglandin E2 (PGE2) levels in NSAID (aspirin) treated rats. The reduction of growth factors such as transforming growth factor-alpha (TGF)-α and vascular endothelial cell growth factor (VEGF) by aspirin was determined by immune-histo-chemistry method. Animals treated with CAA (25 and 50mg/kg) showed significant protection against aspirin induced toxicity by expressing significant increase in PGE2,TGF-α, VEGF expression and along with a noticeable inhibition of nitric oxide and regulating the cytokines levels in rats. The result of the study concluded that CAA prevents gastric ulcer formation due to its immunomodulatory effect, antioxidant potential along with ability to modulate PG synthesis and up regulation of the growth factors⁷⁴.

Hepatoprotective activity

A study was conducted to evaluate the hepatoprotective effect of methanol extract of C. quadrangularis against rifampicin induced hepatotoxicity in rats. In wistar rats liver damage was induced by administering rifampicin (54 mg/kg, p.o.) once daily for 30 days and Methanol extract of C. quadrangularis (500 mg/kg, p.o.) was administered 1hr prior to the administration of rifampicin once daily for 30 days. Silymarin (50mg/kg, p.o) used as reference drug. Results of study concluded that pretreatment of rats with methanol extract of C. quadrangularis there was significant reduction in increased level of aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin due to rifampicin induced toxicity. Also rifampicin administration significantly elevated lipid peroxidation and reduced antioxidant activities like reduced glutathione, superoxide dismutase and catalase. Pretreatment of rats with methanol extract significantly reduced lipid peroxidation and increased the antioxidant activities. Hepatoprotective activity of C. quadrangularis further supported by histology of the liver section of animals treated with the methanol extract. β-carotene may be responsible for its antioxidant activity⁷⁵.

Another similar study was conducted to determine the hepatoprotective of C. quadrangularis against Isoniazid induced hepatotoxicity, the results were same as above. Study suggested that Hepatoprotective effect may be due to antioxidant property⁷⁶.

Anticancer activity

An in-vitro study was conducted to explore the anticancer activity of C. quadrangularis along with its safety profile on normal skin cells. For this purpose spheroid HeLa culture in vitro model was generated to evaluate the response of ethanolic extract of C. quadrangularis on the growth of HeLa tumoroid. Observation of the study indicated that C. quadrangularis selectively induced cytotoxicity, ROS liberation and G1 phase cell cycle arrested only in HeLa cancer cells without affecting the normal skin cells at similar dose. It also significantly inhibited growth of tumoroid and eventually leaded to cell death as exhibited by phase contrast microscopy. Therefore it can be concluded that C. quadrangularis extract had targeted anticancer activity⁷⁷.

In another study ethanol and chloroform extract showed anticancer activity. The IC₅₀ value was found to be at the concentration of 62.5 µg/ml against HeLa cell line and 125 µg/ml in vitro cell line respectively. Cell death in HeLa cell line was studied and confirmed as apoptosis by DNA fragmentation experiments⁷⁸ .

Antiviral activity

In a study partially purified methanolic extract of C. quadrangularis had been investigated for antiviral activity. Partially purified compound of methanolic extract of C. quadrangularis was screened for antiviral activity.

For this in-vitro antiviral activity against Herpes simplex virus (HSV) type 1 and 2 and vero cells at non cytotoxic concentration were determined. In observation HSV1 and HSV2 showed more sensitivity against the purified compound methanolic extract of C. quadrangularis. Results of study confirmed high antiviral activity of partially purified compound⁷⁹.

Antihemorrhoidal activity

In Asia and Africa C. quadrangularis is used for many disorders especially for the treatment of haemorrhoid. To confirm this, effects associated with haemorrhoid like analgesic and anti inflammatory activities as well as venotonic effect of the methanol extract of C. quadrangularis were evaluated in comparison with reference drugs. In results extract exhibited venotonic effect on isolated human umbilical vein similarly to the mixture of bioflavanoids i.e. 90% diosmin and 10 % hisperidin. As the combination of flavanoids (90%diosmin and 10% hisperidin) used clinically for the treatment of haemorrhoid was reported to have analgesic anti inflammatory and venotonic effect. Phytochemical analysis showed that C. quadrangularis is enriched with flavanoids and it is reported that anti inflammatory activity of methanol extract of plant may be due to the presence of flavanoids such as leutolin and β-sitosterol. The venotonic effect of C. quadrangularis also may be produced due to the effect of flavanoids present in the extract which act in same way as that of diosmin and heperidin. This study confirmed use of C. quadrangularis as antihemorrhoidal remedy by folk users in various countries⁸⁰.

Nutritional value of Cissus quadrangularis

C. quadrangularis is used to treat various health disorders as well as it is very nutritious plant to eat. 100 gram of Cissus powder contains protein 6.44g, fat 0.73g, carbohydrate 63.73g, crude fibre 74.36g and total energy 284.55g. The cissus powder is rich in crude fibre, it also contain vitamins/antioxidants vitamin C and beta carotene. The product prepared using cissus powder blended with rice flour in the ratio of 1:3 (25+75g) is highly acceptable by consumers⁸¹.

The plant is also used as a common food supplement in southern India and to treat cardiovascular disorders⁷⁴.

Dosage: The typical recommended daily dosage of cissus extract as reported is between 100and500 mg depending upon the concentration of extract and the severity of symptoms for the powder of the dried plants. The Ayurvedic literature recommends a dosage of 3-6 g to accelerate fracture healing. Safety studies showed no toxic effect at dosage as high as 200mg/kg of body weight. It is also quite safe in either the dried powder form or the commercially available extract⁸². Now a days formulations contain extracts of C. quadrangularis in combination with other active ingredients, used for purpose of management of overweight and obesity, as well as complications associated with these complications specially metabolic syndrome (syndrome X)³.

CONCLUSION:

C. quadrangularis has been used for treating various disorders as traditional medicines in different parts of the world. Each part of the plant possess therapeutic efficacy against different disorders. But there is a need to conduct more clinical and pathological studies to investigate the active potentials of bioactive compounds present in this plant. India is a land of medicinal plants. Many important traditional plants of India have been patented by other countries. Therefore, it is very essential for the researchers to have a proper documentation of herbs of Indian origin so as to save our genera from being patented by others. Moreover, the researchers require performing a systematic documentation of the plants to provide a meaningful and safe use of medicinal plants to promote the traditional knowledge of medicinal plants.

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Received on 17.09.2017 Modified on 22.10.2017

Res. J. Pharmacognosy and Phytochem. 2018; 10(1): 81-90.

DOI: 10.5958/0975-4385.2018.00014.6