INTRODUCTION:

Medicinal plants have been a cornerstone of traditional medicine for centuries and continue to be a vital source for modern drug discovery. Cayratia trifolia (L.) Domin, belonging to the family Vitaceae, is a perennial climber known widely by common names such as 'Fox Grape' in English and 'Amlabel' in Hindi It is distributed throughout the hotter parts of India, as well as in other regions of Asia and Australia.^1,2

This plant holds a significant place in various indigenous systems of medicine for treating a wide array of ailments. Traditionally, different parts of the plant, including the roots, tubers, leaves, and seeds, have been employed to manage conditions ranging from diabetes and tumors to skin diseases and snake bites.³

In recent years, C. trifolia has garnered considerable scientific attention, leading to numerous in-vitro and in-vivo studies to validate its traditional claims. These studies have revealed a plant rich in potent bioactive compounds, including stilbenes (like resveratrol), flavonoids, and terpenoids, which are responsible for its diverse pharmacological activities. This review aims to provide a comprehensive summary of the existing literature on the traditional uses, phytochemistry, and documented pharmacological properties of Cayratia trifolia, while also highlighting areas for future research.³

Methodology of Literature Review:

This review was conducted following a systematic literature review approach to comprehensively collect and evaluate available scientific evidence on Cayratia trifolia (L.) Domin. Electronic databases including PubMed, Scopus, Google Scholar, Web of Science, and ScienceDirect were searched. Keywords used for the literature search included “Cayratia trifolia”, “Cayratia trifolia pharmacology”, “Cayratia trifolia phytochemistry”, “stilbenes”, “flavonoids”, “antidiabetic activity”, “anti-inflammatory activity”, and “traditional uses”.

The literature search covered studies published between 2000 and 2024. Inclusion criteria comprised peer-reviewed original research articles, review articles, and ethnobotanical reports published in the English language. Studies unrelated to Cayratia trifolia, lacking experimental validation, or based on non-scientific sources were excluded. After removal of duplicates, titles and abstracts were screened for relevance, followed by full-text evaluation. Selected studies were categorized under ethnobotany, phytochemistry, pharmacological activities, toxicology, and translational relevance.

Traditional and Ethnobotanical Uses:

The traditional applications of Cayratia trifolia are extensive and well-documented. An infusion of the seeds, along with tuber extract, is traditionally given orally to diabetic patients to manage blood sugar levels. The paste of the tuber is also a common folk remedy applied to the affected area in cases of snake bite.^1,2

The roots, in particular, are highly valued. When ground with black pepper, they are applied as a poultice to treat boils². The whole plant is used as a diuretic and is also employed in the treatment of tumors, neuralgia, and splenopathy^1,3 In veterinary folk medicine, a poultice of the leaves is used to treat yoke sores on bullocks, while the climbers are wrapped around the neck of frantic animals. Furthermore, a decoction of the leaves and roots is used as a diaphoretic to manage high fevers⁴

Botanical Profile:

Botanical Name: Cayratia trifolia (L.) Domin

Family: Vitaceae

Common Names: Fox grape, Three-leaf cayratia (English)

Amalbel, (Hindi)

Amlavetasa, (Ayurveda)

Ambatvel (Marathi)

Synonyms:

Vitis trifolia L.,

Cissus trifolia (L.)

Willd, Causonis trifolia

Taxonomical Classification:

Kingdom: Plantae

Division: Magnoliophyta

Class: Magnoliopsida

Order: Vitales

Family: Vitaceae

Genus: Cayratia

Species: Cayratia trifolia

Phytochemical Constituents:

The diverse medicinal properties of Cayratia trifolia are directly attributable to its complex phytochemical profile. Extensive studies have led to the isolation and characterization of numerous secondary metabolites, with phenolic compounds—specifically stilbenes and flavonoids—being the most prominent.⁴

Stilbenes:

The stilbenoids are a hallmark of the Vitaceae family, and C. trifolia is a particularly rich source of stilbene oligomers. These compounds are believed to be the primary contributors to many of its therapeutic effects ⁵

Key stilbenes isolated from the plant include:

Pallidol

Parthenocissin A

Amurensin

trans-Resveratrol

ε-Viniferin

Ampelopsin C^5,6

These compounds are found in various parts of the plant, including the stems, leaves, and tubers, and are a major focus of pharmacological research.⁶

Flavonoids:

Flavonoids are another major class of phenolic compounds abundant in C. trifolia. These compounds are well-known for their potent antioxidant and anti-inflammatory properties. The primary flavonoids identified are: Kaempferol

Quercetin

Apigenin

Luteolin

Myricetin

And their respective glycosides.^7,8

These flavonoids are often extracted using polar solvents like methanol or ethanol and contribute significantly to the plant's overall antioxidant capacity.

Terpenoids and Steroids:

Phytochemical screening has also confirmed the presence of various triterpenoids and steroids. The most commonly reported steroid is β-sitosterol, a well-known compound with anti-inflammatory and cholesterol-lowering properties. Other triterpenoids and saponins have also been detected in the tuber and leaf extracts, contributing to the plant's diverse ethnobotanical uses.^1,3

Other Constituents:

In addition to the major classes above, preliminary phytochemical analyses have confirmed the presence of other groups of compounds. These include tannins (both condensed and hydrolysable), alkaloids, glycosides, and fixed oils/fatty acids⁷. These compounds, while perhaps less studied, likely contribute synergistically to the plant's overall pharmacological profile.

Table 1: Summary of Traditional and Ethnobotanical Uses of Cayratia trifolia:

Plant Part	Traditional Use/Method of Preparation	Ailment or Condition Treated
Seeds and Tubers	Infusion of seeds; Tuber extract (oral)	Diabetes (to manage blood sugar)
Tubers	Paste (applied topically)	Snake bites
Roots	Ground with black pepper (as a poultice)	Boils
Roots	Decoction (oral)	Diaphoretic (to manage high fevers)
Leaves	Decoction (oral)	Diaphoretic (to manage high fevers)
Leaves	Poultice (topical)	Yoke sores on bullocks (Veterinary)
Whole Plant	Used as a diuretic	Edema/Water retention
Whole Plant	(Specific preparations not listed)	Tumors, Neuralgia, Splenopathy
Climbers (Stems)	Wrapped around the neck	Frantic animals (Veterinary)

Pharmacological Activities:

The extensive traditional use of Cayratia trifolia has been substantiated by numerous modern pharmacological studies. These investigations, ranging from in-vitro assays to in-vivo animal models, have validated its role as a potent therapeutic agent. The rich phytoconstituents, particularly stilbenes and flavonoids, are the primary drivers of this diverse bioactivity.^9,10

Antidiabetic Activity:

The traditional claim of C. trifolia as an antidiabetic agent is one of its most extensively studied properties. Both in-vivo and in-vitro models have demonstrated significant hypoglycemic effects, operating through multiple mechanisms.

In-Vivo Hypoglycemic Effects: Studies using diabetic rat models, induced by either streptozotocin (STZ) or alloxan, have consistently shown the efficacy of C. trifolia extracts. Administration of ethanolic and ethyl acetate extracts of the roots resulted in a significant, dose-dependent reduction in fasting blood glucose levels. This effect was often comparable to the standard drug, metformin Beyond glycemic control, the extracts also corrected associated metabolic abnormalities,such as improving serum insulin levels, normalizing the lipid profile (reducing total cholesterol and triglycerides), and restoring key liver and kidney function markers.^9,10 One study suggested this effect may be due to the flavonoid content improving the function of damaged pancreatic β-cells.^9,10

Mechanisms of Action:

Inhibition of Carbohydrate-Digesting Enzymes: In-vitro assays have confirmed that leaf extracts of C. trifolia potently inhibit α-glucosidase and α-amylase. A 50% ethanol extract, in particular, showed superior α-glucosidase inhibitory activity, even surpassing the standard drug acarbose in some studies This mechanism is critical as it slows the breakdown of carbohydrates in the intestine, leading to a reduced postprandial glucose spike.¹¹

Enhanced Peripheral Glucose Uptake: The plant's extracts appear to work at the cellular level. An in-vitro study using an isolated rat hemi-diaphragm model demonstrated that the ethanolic extract significantly increased glucose uptake from the blood into muscle tissue. This suggests a direct peripheral action, possibly by improving insulin sensitivity or modulating glucose transporters like GLUT-4.¹²

Antioxidant Activity:

A strong antioxidant capacity is foundational to many of the plant's other pharmacological effects, particularly its antidiabetic and anti-inflammatory properties.

In-Vitro Free Radical Scavenging: C. trifolia extracts (especially from leaves and stems) have shown powerful free radical scavenging abilities in numerous antioxidant assays, including the DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)), and nitric oxide scavenging assays. This activity is strongly correlated with the high total phenolic and flavonoid content, with compounds like quercetin and resveratrol being major contributors.^8,13

n-Vivo Antioxidant Effects: The plant's antioxidant potential has also been confirmed in vivo. In diabetic rats treated with C. trifolia root extract, a significant restoration of endogenous antioxidant enzyme levels was observed. The levels of superoxide dismutase (SOD) and catalase, which are typically depleted by oxidative stress in diabetes, were significantly increased, demonstrating the extract's ability to restore the body's redox balance. This complementary antioxidant action likely helps protect the pancreas and other organs from the oxidative damage that accompanies chronic hyperglycemia.⁹

Anti-inflammatory and Analgesic Activity:

Chronic inflammation underlies many diseases, and traditional medicine frequently uses C. trifolia to manage inflammatory conditions like boils. Modern studies have validated this use, showing that the plant's extracts possess significant anti-inflammatory and pain-relieving (analgesic) properties.

Anti-inflammatory Effects: In-vivo studies using the carrageenan-induced paw edema model in rats, a standard test for acute inflammation, have shown that the ethanolic extract of C. trifolia (particularly from the root) can significantly inhibit edema (swelling) in a dose-dependent manner. This effect is often attributed to the inhibition of inflammatory mediators like prostaglandins and histamine, likely due to the high concentration of flavonoids and stilbenes, which are known to inhibit enzymes like cyclooxygenase (COX) and lipoxygenase (LOX)^14,15.

Analgesic Effects: The plant's analgesic properties have been demonstrated using both thermal and chemical pain models. In the "hot plate" test, the extract increased the pain threshold, indicating a centrally acting analgesic effect. In the "acetic acid-induced writhing" test, which models peripheral pain, the extract significantly reduced the number of writhes, suggesting an inhibition of peripheral pain mediators¹⁴. This dual action (central and peripheral) makes it a particularly interesting candidate for pain management.

Antimicrobial and Antiviral Activity:

Antibacterial and Antifungal:

Extracts from various parts of C. trifolia (leaves, stem, and root) have been tested against a broad spectrum of human pathogens. Using the agar well diffusion method, methanolic and ethanolic extracts have shown significant zones of inhibition against Gram-positive bacteria, such as Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa. The plant also exhibits antifungal activity against opportunistic pathogens like Candida albicans and Aspergillus niger. This broad-spectrum activity supports its traditional use in treating skin diseases and infections.^8,16

Antiviral Activity: While less studied than its antibacterial properties, preliminary research has shown potential antiviral effects. Specific stilbene oligomers isolated from C. trifolia have been investigated for their ability to inhibit viral replication, opening a promising new avenue for research¹⁷.

Anticancer and Cytotoxic Activity:

The cytotoxic potential of C. trifolia against various cancer cell lines is a rapidly emerging area of research. The stilbene oligomers, which are characteristic of this plant, are the primary focus of these investigations.

In-Vitro Cytotoxicity: Stilbenes like pallidol and parthenocissin A, isolated from C. trifolia, have demonstrated potent cytotoxic effects against several human cancer cell lines, including breast (MCF-7), colon (HCT-116), and liver (HepG2) cancer cells^17,18.

Mechanisms of Action: The proposed mechanisms for this anticancer effect are multifaceted. These bioactive compounds appear to induce apoptosis (programmed cell death) by activating the caspase signaling cascade. Furthermore, they have been shown to cause cell cycle arrest, effectively stopping the uncontrolled proliferation of cancer cells at different phases (e.g., G1/S or G2/M), thus preventing tumor growth¹⁸. This research, while still largely preclinical, highlights C. trifolia as a valuable source for the discovery of new anticancer lead compounds.

Hepatoprotective Activity:

The liver, being the primary site of metabolism, is highly susceptible to drug- and toxin-induced injury. Several studies have investigated the potential of C. trifolia to protect the liver from such damage.

In-Vivo Models: In animal models where liver damage was induced using hepatotoxins like paracetamol (PCM) or carbon tetrachloride (CCl₄), pretreatment with the ethanolic extract of C. trifolia root showed significant hepatoprotection. This was evidenced by a substantial decrease in elevated liver enzyme markers, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), compared to the toxin-treated control group¹⁹. Histopathological examination of the liver tissues from the extract-treated group also showed a marked reduction in cellular necrosis and fatty infiltration, confirming the protective effect at a cellular level. This protection is strongly linked to the plant's high antioxidant content, which mitigates the oxidative stress caused by the toxins.^19,20

Anti-ulcer Activity:

Traditionally, C. trifolia has been used for gastrointestinal complaints. Scientific studies have validated its anti-ulcer potential using in-vivo models, such as ethanol-induced or pylorus ligation-induced ulcers in rats.

Gastroprotective Effects:

Oral administration of the plant's extract demonstrated a significant reduction in the ulcer index, total acidity, and gastric juice volume, while concurrently increasing the gastric pH and mucus content. The mechanism appears to be twofold: cytoprotective (by enhancing the gastric mucosal barrier, possibly by increasing prostaglandin secretion) and anti-secretory (by reducing the secretion of gastric acid)¹⁵. This validates its traditional use for managing gastric ulcers.

Other Activities:

Preliminary research has indicated a wide range of other potential therapeutic effects for C. trifolia. These include:

Larvicidal Activity:

The leaf extract has shown potent larvicidal activity against mosquito species like Aedes aegypti, the vector for dengue fever. This suggests its potential as a source for natural, eco-friendly insecticides.²¹

Neuroprotective and Cardioprotective Effects:

While this area is still emerging, the potent antioxidant and anti-inflammatory properties of the stilbene compounds (like resveratrol and viniferin) suggest a strong potential for protecting against neurodegenerative diseases and cardiovascular complications. These compounds are known to cross the blood-brain barrier and mitigate oxidative stress in neural tissues, but more direct research using C. trifolia extracts is needed.^9,21

Comparative and Critical Evaluation of Studies:

Although multiple studies confirm the pharmacological potential of Cayratia trifolia, considerable variability exists across reports. Differences in plant parts used (roots, leaves, tubers), extraction solvents (aqueous, ethanolic, ethyl acetate), and dose ranges upto (2000 mg/kg) significantly influence experimental outcomes. ^10,14

Ethanolic extracts generally demonstrate superior bioactivity compared to aqueous extracts, likely due to improved extraction of polyphenolic compounds. Root and tuber extracts show stronger antidiabetic and anti-inflammatory effects than leaf extracts, correlating with higher stilbene content. However, the lack of standardized extraction protocols and phytochemical quantification limits direct comparison across studies.

Furthermore, most investigations rely on acute or short-term models, with limited reproducibility across laboratories. These inconsistencies highlight the need for standardized extract preparation, dose normalization, and multi-center validation studies.

Toxicology and Safety Studies:

For any potential therapeutic agent, especially a traditional medicine, establishing a safety profile is as important as proving its efficacy.

Acute Toxicity Studies:

Acute oral toxicity studies, conducted in accordance with OECD guidelines, have generally found C. trifolia extracts to be safe at high doses. Studies in mice and rats have shown that a single oral dose (up to 2000mg/kg) of the ethanolic or aqueous extract does not produce any signs of toxicity or mortality within the 14-day observation period. This indicates a high LD₅₀ (Lethal Dose, 50%) and a wide margin of safety for acute administration.^10,14

Sub-chronic Toxicity: While acute studies are promising, more long-term (sub-chronic) toxicity studies are needed to evaluate the effects of repeated dosing, which would be more representative of its traditional use.

Clinical Relevance and Translational Challenges:

Despite extensive preclinical evidence supporting the therapeutic potential of Cayratia trifolia, translation into clinical application remains unaddressed. Major challenges include the absence of human clinical trials, lack of standardized herbal formulations, and batch-to-batch variability in phytochemical composition.

Regulatory hurdles, including compliance with Good Manufacturing Practices (GMP) and herbal drug standardization guidelines, further complicate clinical translation. Additionally, pharmacokinetic parameters, herb–drug interactions, and long-term safety profiles remain unexplored.

Future translational research should focus on standardized extracts, bioavailability enhancement, toxicological evaluation under chronic dosing, and well-designed randomized clinical trials to establish safety and efficacy in humans.

CONCLUSION:

This review confirms that Cayratia trifolia (L.) Domin is a medicinal plant of significant therapeutic value, successfully transitioning from a traditional remedy to a scientifically validated pharmacological resource. The plant is a rich reservoir of potent phytochemicals, particularly stilbene oligomers (e.g., pallidol, resveratrol) and flavonoids (e.g., quercetin), which are the primary drivers of its wide-spectrum bioactivity.

Preclinical evidence is most robust for its antidiabetic activity (mediated by $\alpha$-glucosidase inhibition and enhanced peripheral glucose uptake), as well as its potent antioxidant, anti-inflammatory, hepatoprotective, and cytotoxic properties. Acute toxicity studies also indicate a wide margin of safety, supporting its traditional use.

However, despite this wealth of promising preclinical data, the translation of C. trifolia into clinical practice is currently limited. To bridge the gap between traditional use and modern medicine, future research must address four critical areas:

1. Bioactivity-Guided Fractionation: Moving beyond crude extracts to isolate and characterize the specific active compounds responsible for pharmacological effects.

2. Molecular Mechanisms: Elucidating the precise signal transduction pathways (e.g., AMPK or PI3K/Akt for diabetes; caspase cascades for cancer) modulated by these bioactive compounds.

3. Chronic Safety Profiling: Conducting sub-chronic and chronic toxicity studies (e.g., 28-day or 90-day repeated dose) to establish long-term safety.

4. Clinical Trials: Initiating well-designed, randomized, placebo-controlled human clinical trials, which remain the most significant missing link in validating C. trifolia as a therapeutic agent.

Focused, multidisciplinary research in these key areas is essential to finally unlock the full therapeutic potential of this promising indigenous plant.

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Received on 04.01.2026 Revised on 07.02.2026

Accepted on 12.03.2026 Published on 21.04.2026

Available online from April 24, 2026

Res. J. Pharmacognosy and Phytochem. 2026; 18(2):143-148.

DOI: 10.52711/0975-4385.2026.00020

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Pharmacological Activity	*In-Vivo/In-Vitro* Model Used	Key Findings and Validated Mechanisms
Antidiabetic⁹	STZ/Alloxan-induced diabetic rats; Isolated rat hemi-diaphragm	(✓) Reduced blood glucose; Restored insulin levels; (✓) Inhibited α-glucosidase and α-amylase; (✓) Increased peripheral glucose uptake.
Antioxidant ⁸	DPPH and ABTS assays; Diabetic rat models (SOD, Catalase)	(✓) Potent free radical scavenging; (✓) Restored endogenous enzymes (SOD, Catalase) depleted by diabetes.
Anti-inflammatory ¹⁴	Carrageenan-induced paw edema (rats)	(✓) Significantly inhibited edema (swelling); Likely by inhibiting COX/LOX pathways.
Analgesic ¹⁴	Hot plate test; Acetic acid-induced writhing	(✓) Increased pain threshold (central effect); (✓) Reduced writhes (peripheral effect).
Antimicrobial ⁸	Agar well diffusion (S. aureus, E. coli, C. albicans)	(✓) Significant zone of inhibition against Gram-positive, Gram-negative, and fungal pathogens.
Anticancer ¹⁷	Human cancer cell lines (MCF-7, HCT-116, HepG2)	(✓) Potent cytotoxicity from isolated stilbenes; (✓) Induced apoptosis (via caspases); Caused cell cycle arrest.
Hepatoprotective ¹⁹	Paracetamol (PCM) / CCl₄-induced liver damage (rats)	(✓) Significantly reduced AST, ALT, ALP; (✓) Reduced cellular necrosis on histopathology.
Anti-ulcer ²⁰	Ethanol-induced ulcers (rats)	(✓) Reduced ulcer index and total acidity; (✓) Increased gastric mucus (Cytoprotective and Anti-secretory).
Toxicology (Safety) ^10,14	Acute oral toxicity (OECD guidelines)	(✓) Found to be safe (LD₅₀ > 2000 mg/kg); No signs of toxicity or mortality.