Cissus vitiginea (Vitaceae) - Wild grapes

Nov 6, 2025

29 min read

Updated: Jul 30

Cissus vitiginea is a woody deciduous climber of the Vitaceae, the grape family, scrambling over scrub vegetation and low trees across the dry deciduous forests of the Indian subcontinent and Southeast Asia. It is a plant of arid resilience: its stems swell with water stored against the long dry season, its leaves are shed to reduce transpiration, and its roots dig deep into rocky substrates. The stem yields a tough, fibrous bast used traditionally for cordage, while the fruits, though meagre and astringent, are consumed by rural communities and wildlife alike. In the Ayurvedic and folk medical systems of India, the root powder and stem paste are applied to fractures, sprains, and inflammatory joint conditions, a practice that has earned the plant its vernacular reputation as a bone-setter. Research from 2025 and 2026 is now interrogating these traditional applications at the molecular level: a methanolic extract of the stem has demonstrated dose-dependent acceleration of fracture healing in a rat tibial defect model, with histomorphometric evidence of increased callus formation and upregulated Runx2 and osteocalcin expression. The same extract exhibited significant COX-2 and 5-LOX inhibition in vitro, providing a mechanistic basis for its anti-inflammatory action in arthritis. Triterpenoids and stilbenoids isolated from the root bark have shown selective cytotoxicity against osteosarcoma cell lines while sparing normal osteoblasts, a finding with implications for bone cancer therapy.

1. Taxonomic Insights

Species: Cissus vitiginea L.

Family: Vitaceae, the Grape Family.

Genus: Cissus.

Basionym: Cissus vitiginea L., Species Plantarum 1: 117 (1753).

Taxonomic Note: The species has been subject to considerable nomenclatural confusion. It has been synonymized under Cissus repanda Vahl, Vitis vitiginea (L.) Wight & Arn., and Cissus angulata Lam. The currently accepted name is Cissus vitiginea L., though regional floras may still reference the synonyms. The genus Cissus is the largest in the Vitaceae, with over 350 species distributed pantropically, and its taxonomy remains fluid pending comprehensive molecular phylogenetic revision.

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Botanical Description

Cissus vitiginea is a large, deciduous, tendril-climbing shrub with a woody stem, often scrambling to 10 metres or more over supporting vegetation. The stem is stout, terete (cylindrical), and swollen at the nodes. Young branches are densely covered with soft, rusty-brown, woolly hairs (tomentose), becoming glabrous and greyish-brown with age. The bark is fibrous and can be peeled in strips, revealing a green inner layer rich in chlorophyll, a xerophytic adaptation allowing photosynthesis during the leafless dry season.

Key Identification Features:

Leaves are simple, alternate, broadly ovate to orbicular, 8 to 20 centimetres long and 7 to 18 centimetres wide. The leaf base is deeply cordate (heart-shaped), the margin is sharply and irregularly toothed (dentate-serrate), and the apex is acute to acuminate. The upper surface is dark green and sparsely hairy to glabrous, while the lower surface is densely white- or rusty-tomentose, a soft, felt-like pubescence that gives the underside of the leaf a characteristic pale colour. Venation is palmate-reticulate, with 5 to 7 prominent veins radiating from the petiole insertion. The petiole is 3 to 10 centimetres long, tomentose. Tendrils are leaf-opposed, simple (unbranched), and robust, coiling around supports to anchor the climbing stems.

The inflorescence is a leaf-opposed, compound, umbellate cyme, 5 to 15 centimetres across, densely hairy. Flowers are small, 3 to 4 millimetres in diameter, greenish-yellow to creamy white, and functionally unisexual (the plant is polygamodioecious, bearing male, female, and sometimes bisexual flowers on separate plants). The calyx is cup-shaped and obscurely 4-lobed. Petals are 4, free, and reflexed at anthesis. Stamens are 4 and inserted opposite the petals. The disc is well-developed, 4-lobed, and nectariferous. The ovary is superior, 2-locular, with a short, subulate style and a small, capitate stigma.

The fruit is a globose to obovoid berry, 6 to 10 millimetres in diameter, green when immature and turning purplish-black to deep red at maturity. It contains 1 to 2 (rarely 3) seeds. The seed is pyriform (pear-shaped), 5 to 7 millimetres long, with a smooth, hard testa and two prominent ventral ridges enclosing a deep pit, a diagnostic feature for distinguishing Cissus seeds from those of other Vitaceae genera.

Distribution: Native to the Indian subcontinent (India, Pakistan, Nepal, Bangladesh, Sri Lanka), Myanmar, and Thailand. It is widely distributed across the dry deciduous forests, scrublands, and thorn forests of peninsular India, from the foothills of the Himalayas to the Deccan Plateau and the Eastern and Western Ghats, ascending to 1,200 metres altitude. It is also reported from dry zones of Southeast Asia. It is not widely cultivated but persists in forest fragments, hedgerows, and village commons.

Conservation Status: The species has not been assessed by the IUCN Red List. Given its wide distribution across the Indian subcontinent and its tolerance of disturbed habitats and dry conditions, it is not considered threatened. However, habitat loss due to deforestation and agricultural expansion is reducing local populations, particularly in densely populated regions. No specific conservation measures are in place. Germplasm is not conserved in major international gene banks, representing a gap for a species with emerging medicinal significance.

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Etymology

The generic name Cissus is derived from the Greek kissos, meaning ivy, an allusion to the climbing habit shared by many members of the genus. The specific epithet vitiginea is Latin, meaning "resembling a vine" or "of the vine" (from vitis, the grapevine, and the adjectival suffix -gineus), a reference to the grape-like leaves and climbing growth that make the plant superficially similar to the cultivated grape, Vitis vinifera. The Hindi vernacular "jangli angoor" translates directly to "wild grape," echoing the Latin binomial.

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2. Common Names

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3. Related Plants from the Vitaceae Family

The Vitaceae is a medium-sized family of about 900 species in 14 genera, predominantly tropical and subtropical lianas and climbers. The family is defined by its tendril-climbing habit, swollen nodes, and small, 4- to 5-merous flowers with a well-developed nectariferous disc. The berries are the characteristic fruit, and the seeds have a distinctive ventral morphology used in taxonomic identification.

Cissus quadrangularis (Hadjod, Asthisamharaka): The most famous medicinal species of the genus and the closest botanical relative with an overlapping pharmacological profile. It is a succulent, quadrangular-stemmed climber, also used traditionally as a bone-setter. It contains ketosteroids and stilbenoids that have demonstrated bone-healing and anti-osteoporotic activity in clinical trials. C. vitiginea is often used as a substitute or adulterant for C. quadrangularis in herbal markets, and their comparative pharmacology is an important area of study.

Cissus verticillata (Insulin Plant, Princess Vine): A Neotropical species widely used in Caribbean and South American traditional medicine for diabetes, inflammation, and respiratory conditions. It shares the genus's richness in stilbenoids and triterpenoids.

Vitis vinifera (Grape): The most economically important member of the family, the source of table grapes, wine, and raisins. Grape seeds and skins contain resveratrol and proanthocyanidins with antioxidant, cardioprotective, and anticancer activities. The medicinal chemistry of Vitis provides a template for investigating the stilbenoid content of Cissus species.

Parthenocissus quinquefolia (Virginia Creeper): A temperate ornamental climber, widely planted for its brilliant autumn foliage. Its tendrils are adhesive-tipped rather than twining, a morphological distinction within the family.

Ampelocissus latifolia (Wild Grape): An Indian relative with edible fruits and traditional medicinal uses for wounds and skin diseases, often confused with Cissus vitiginea in rural areas. The two are distinguished by the compound leaves and branched tendrils of Ampelocissus.

Cayratia trifolia (Fox Grape): Another Indian Vitaceae climber with trifoliolate leaves, used in traditional medicine for ulcers and wounds. It is a common associate of C. vitiginea in dry deciduous forests.

Leea species: Once placed in a separate family (Leeaceae) but now phylogenetically nested within the Vitaceae. Leea indica and Leea macrophylla are used in Ayurvedic medicine for wounds, diabetes, and as cardiotonics, sharing some pharmacological overlap with Cissus.

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4. Medicinal Uses: Summary of Primary and Secondary Actions

Primary Actions:

Bone Healing (Osteogenic Activity): Cissus vitiginea is primarily known as a traditional bone-setter. The stem and root, prepared as a paste, are applied externally over fractures and sprains, and a decoction is taken internally. Animal studies now confirm that methanolic extracts of the stem accelerate fracture healing, with increased callus volume, higher bone mineral density at the fracture site, and upregulated expression of the osteogenic transcription factor Runx2 and its downstream target osteocalcin. The bone-healing activity is attributed to triterpenoids and stilbenoids that stimulate osteoblast proliferation and differentiation.

Anti-inflammatory: Extracts of the stem and root inhibit the cyclooxygenase (COX-2) and 5-lipoxygenase (5-LOX) enzymes, the two principal pathways of arachidonic acid metabolism that generate prostaglandins and leukotrienes, respectively. This dual inhibition provides a mechanistic basis for the traditional use of C. vitiginea in inflammatory joint conditions, rheumatoid arthritis, and gout. The anti-inflammatory potency is comparable to that of Cissus quadrangularis, supporting its use as a substitute species.

Antioxidant: The stem and leaves contain phenolic compounds, flavonoids, and stilbenoids with significant radical-scavenging activity in DPPH, ABTS, and FRAP assays. The antioxidant capacity correlates with total phenolic content and provides a mechanistic underpinning for the plant's protective effects on cartilage and bone, tissues vulnerable to oxidative stress-induced degeneration.

Analgesic: Animal studies using the hot-plate and acetic acid-induced writhing models demonstrate dose-dependent analgesic activity of stem extracts, supporting the traditional use for painful conditions including fractures, sprains, and arthritis.

Antimicrobial: Stem and leaf extracts show moderate to strong activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The activity is attributed to phenolic compounds, triterpenoids, and stilbenoids. This supports the traditional application of the leaf paste to infected wounds and skin conditions.

Anti-arthritic: Beyond general anti-inflammatory activity, C. vitiginea extracts have shown specific chondroprotective effects in vitro, reducing the expression of matrix metalloproteinases (MMPs) that degrade cartilage collagen and proteoglycans. This positions the plant as a candidate for development as a disease-modifying agent for osteoarthritis.

Secondary Actions:

Antidiabetic: Preliminary animal studies suggest a blood-glucose-lowering effect of leaf extracts in alloxan-induced diabetic rats. The mechanism (insulin sensitization, alpha-glucosidase inhibition, or beta-cell protection) is not characterized.

Hepatoprotective: Root extracts have shown protection against carbon tetrachloride-induced hepatotoxicity in rat models, reducing serum transaminases and preserving hepatic glutathione levels.

Anthelmintic: The stem and root are used traditionally as an anthelmintic. In vitro studies on earthworm paralysis time provide weak supportive evidence.

Antipyretic: Leaf and stem decoctions are used in traditional medicine to reduce fever. Animal studies using brewer's yeast-induced pyrexia show a modest antipyretic effect.

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Medicinal Parts

Stem: The most widely used and commercially significant part. The stem is the primary source of the osteogenic and anti-inflammatory compounds. It is harvested, dried, powdered, and applied as a paste for fractures, or decocted for internal consumption. The fibrous bark is stripped before use.

Root: Also used for fracture healing and inflammatory conditions, often considered more potent than the stem. The root bark is particularly rich in triterpenoids and stilbenoids. Unsustainable root harvesting poses a conservation concern for wild populations.

Leaves: Applied as a paste to wounds, boils, and skin infections. The leaf decoction is taken internally for fever and digestive complaints. The leaves have lower concentrations of the bioactive triterpenoids than the stem and root.

Fruits: Edible but astringent, consumed by rural communities and used in traditional medicine for digestive disorders. The fruit is not a major medicinal part.

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5. Phytochemistry

5.1 Triterpenoids

Triterpenoids are the dominant bioactive class in Cissus vitiginea and are likely the primary mediators of the osteogenic and anti-inflammatory activities.

Friedelin: A pentacyclic triterpene ketone widely distributed in the Vitaceae. It has demonstrated anti-inflammatory, analgesic, and antipyretic activities in animal models. Friedelin is present in the stem bark and root.

Epifriedelanol: The hydroxylated derivative of friedelin, with similar biological activities. It has shown gastroprotective and anti-ulcer activity in some studies, relevant to the traditional use of the plant for gastric complaints.

Beta-sitosterol: A common phytosterol with anti-inflammatory, cholesterol-lowering, and mild estrogenic activity. It is present in the stem and root and may contribute to the bone-healing effect through estrogen receptor-mediated stimulation of osteoblast activity.

Lupeol: A pentacyclic triterpene with potent anti-inflammatory activity, acting through inhibition of NF-κB and suppression of COX-2 and iNOS expression. Lupeol is present in the stem bark.

Alpha-amyrin and Beta-amyrin: Pentacyclic triterpenes with anti-inflammatory and analgesic activities. They are common constituents of the leaf and stem wax.

5.2 Stilbenoids

Stilbenoids are polyphenolic compounds characteristic of the Vitaceae, most famously resveratrol from Vitis vinifera. Their presence in Cissus vitiginea is of significant pharmacological interest.

Resveratrol: The parent stilbenoid, with antioxidant, anti-inflammatory, cardioprotective, and anticancer activities. It activates SIRT1 (sirtuin 1), an NAD+-dependent deacetylase involved in cellular stress resistance and longevity. Resveratrol is reported from the stem and root of C. vitiginea.

Piceatannol: A hydroxylated analogue of resveratrol, with more potent antioxidant and anti-inflammatory activity. It inhibits COX-2, 5-LOX, and IκB kinase, blocking NF-κB activation. Piceatannol has been isolated from the root bark and is likely a major contributor to the anti-inflammatory and anti-arthritic activity.

Viniferins: Resveratrol oligomers (dimers, trimers) with enhanced bioactivity compared to the monomer. Epsilon-viniferin and delta-viniferin have been reported from related Cissus species and are likely present in C. vitiginea, though specific isolation studies are lacking.

5.3 Flavonoids and Phenolic Acids

Quercetin and Kaempferol: Flavonol glycosides present in the leaves and stems, contributing to the antioxidant and anti-inflammatory activity.

Catechin and Epicatechin: Flavan-3-ols found in the stem bark, with antioxidant and collagen-stabilizing properties, potentially contributing to the bone-healing effect.

Gallic Acid, Ellagic Acid, and Chlorogenic Acid: Phenolic acids present in the leaves and stem, providing antioxidant and antimicrobial activity.

5.4 Vitamins and Minerals

The stem and root contain calcium, phosphorus, and magnesium, minerals relevant to bone mineralization. While the concentrations are insufficient to explain the bone-healing activity solely through mineral supplementation, the presence of bioavailable calcium and magnesium may contribute to the overall effect when combined with the osteogenic triterpenoids and stilbenoids.

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6. Mechanisms of Action

6.1 Osteogenic Activity and Fracture Healing

The acceleration of fracture healing by Cissus vitiginea extracts operates through multiple, synergistic mechanisms. Triterpenoids, including friedelin, epifriedelanol, and lupeol, stimulate the proliferation and differentiation of mesenchymal stem cells into osteoblasts, the bone-forming cells. This effect is mediated, at least in part, through the activation of the Wnt/beta-catenin signaling pathway and the upregulation of Runx2, the master transcription factor for osteoblast differentiation. Runx2, in turn, drives the expression of bone matrix proteins including osteocalcin, osteopontin, and type I collagen.

Stilbenoids, particularly resveratrol and piceatannol, activate SIRT1 and estrogen receptor-alpha (ER-alpha) in osteoblasts, promoting cell survival, differentiation, and mineralization. Resveratrol also suppresses the differentiation of osteoclasts, the bone-resorbing cells, through inhibition of RANKL-induced NF-κB and NFATc1 signaling. This dual action, promoting bone formation and suppressing bone resorption, tilts the remodeling balance toward net bone gain.

The anti-inflammatory activity of the extract, through COX-2 and 5-LOX inhibition, reduces the production of prostaglandins and leukotrienes at the fracture site. While acute inflammation is necessary for the initiation of fracture healing, excessive or prolonged inflammation impairs callus maturation and remodeling. The extract appears to modulate, rather than suppress, the inflammatory phase, accelerating the transition to the reparative phase. The 2025 study confirmed these effects histologically: treated animals showed a larger, more organized callus with a higher proportion of mineralized tissue and stronger biomechanical properties.

6.2 Anti-inflammatory Activity: Dual Inhibition of COX-2 and 5-LOX

The arachidonic acid cascade is the central pathway generating pro-inflammatory lipid mediators. COX-2 metabolizes arachidonic acid to prostaglandins (PGE2, PGI2), while 5-LOX metabolizes it to leukotrienes (LTB4, LTC4). Most non-steroidal anti-inflammatory drugs (NSAIDs) inhibit only the COX pathway; leukotriene production continues unchecked, and in some cases, arachidonic acid is shunted toward the 5-LOX pathway, a phenomenon called the leukotriene shunt. Dual COX/LOX inhibitors offer a superior anti-inflammatory profile by blocking both arms of the cascade.

Cissus vitiginea extracts inhibit both COX-2 and 5-LOX in vitro, with IC50 values in the low microgram per millilitre range. The responsible compounds are likely the stilbenoids piceatannol and resveratrol, which directly bind to and inhibit both enzymes, and the triterpenoids lupeol and beta-sitosterol, which suppress the NF-κB-mediated transcriptional upregulation of COX-2. This dual inhibition is pharmacologically significant and positions C. vitiginea as a candidate for development as a natural anti-inflammatory with a potentially superior gastrointestinal safety profile compared to conventional COX-selective NSAIDs. The traditional use for arthritis, where both prostaglandins and leukotrienes contribute to joint inflammation and cartilage degradation, is mechanistically validated by this profile.

6.3 Chondroprotection and Anti-arthritic Activity

Osteoarthritis is characterized by the progressive degradation of articular cartilage, driven by matrix metalloproteinases (MMPs) and aggrecanases produced by chondrocytes under the influence of pro-inflammatory cytokines (IL-1β, TNF-α). Cissus vitiginea extracts have been shown to reduce MMP-3 and MMP-13 expression in IL-1β-stimulated chondrocytes in vitro. The mechanism involves the inhibition of NF-κB and MAP kinase (ERK, p38, JNK) signaling pathways by stilbenoids and triterpenoids, reducing the transcription of MMP genes. Simultaneously, the extracts upregulate the expression of tissue inhibitors of metalloproteinases (TIMPs), restoring the MMP/TIMP balance. This dual modulation, suppressing catabolic enzymes and enhancing their natural inhibitors, constitutes a chondroprotective mechanism that addresses the underlying disease process, not just the symptoms, of osteoarthritis. Animal studies in monoiodoacetate (MIA)-induced arthritis models show reduced cartilage loss and improved joint architecture scores with C. vitiginea treatment, confirming the in vitro findings in a whole-organism context.

6.4 Antimicrobial Activity

The antimicrobial activity of C. vitiginea extracts is attributed to the combined action of phenolics, stilbenoids, and triterpenoids. These compounds disrupt bacterial cell membranes, increasing permeability and causing leakage of intracellular contents. Piceatannol and resveratrol also inhibit bacterial DNA gyrase and topoisomerase IV, enzymes essential for DNA replication. The activity against Staphylococcus aureus, including some methicillin-resistant strains, is noteworthy and supports the traditional application of leaf and stem paste to infected wounds and skin conditions. The triterpenoids friedelin and lupeol contribute to the antimicrobial profile through a less specific, membrane-active mechanism.

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7. Traditional and Ethnobotanical Uses

7.1 Bone Fractures and Dislocations (Asthibhagna)

Formulation: Stem or root paste, applied externally; stem or root decoction, taken internally.

Preparation and Use: This is the signature traditional use of Cissus vitiginea. The fresh stem or root is washed, and the outer bark is scraped away. The inner tissue is pounded or ground into a fine paste, often mixed with a small amount of lime (calcium hydroxide) or turmeric paste. This paste is applied directly over the fracture site after the bone has been set and immobilized with splints of bamboo or wood. The paste dries to a hard, protective cast, providing both pharmacological and mechanical support. A decoction of the dried stem or root powder, typically 5 to 10 grams boiled in 200 millilitres of water and reduced to half, is administered orally once or twice daily to accelerate healing from within. This practice is widespread among traditional bone-setters (vaidyas) across rural India, from Rajasthan to Tamil Nadu.

Scientific Validation: The 2025 fracture healing study in rats, demonstrating accelerated callus formation, increased Runx2 and osteocalcin expression, and improved biomechanical strength, provides strong preclinical validation for this ancient practice. The combined internal and external application, a defining feature of the traditional protocol, is pharmacologically rational: external application provides local anti-inflammatory and antimicrobial activity at the wound site, while internal consumption delivers systemic osteogenic compounds.

7.2 Arthritis, Joint Pain, and Gout (Sandhivata, Amavata)

Formulation: Stem powder with warm water or milk; stem paste applied to swollen joints.

Preparation and Use: The dried stem is powdered and mixed with warm water or milk to form a thick paste or a drinkable slurry. This is consumed once or twice daily, often on an empty stomach, for the relief of joint pain, swelling, and stiffness. For acutely inflamed joints, the same paste is applied externally as a poultice. The treatment is typically continued for several weeks. In some traditions, the root powder is preferred for arthritis, being considered more potent.

Scientific Validation: The dual COX-2/5-LOX inhibition, the chondroprotective activity demonstrated in vitro, and the analgesic effect in animal models all support this use. The anti-arthritic mechanism addresses both inflammation and cartilage degradation, the two hallmarks of the disease.

7.3 Wound Healing and Skin Infections (Vrana)

Formulation: Leaf or stem paste.

Preparation and Use: Fresh leaves or young stems are crushed into a paste and applied directly to cuts, abrasions, boils, and skin infections. The paste is covered with a clean cloth and changed daily. The astringent and antimicrobial properties of the plant are valued for wound management.

Scientific Validation: The in vitro antimicrobial activity against S. aureus and other wound pathogens, combined with the anti-inflammatory and antioxidant properties, provides a rational basis for this use. The tannins present in the leaves contribute an astringent effect that contracts tissues and reduces exudation.

7.4 Fever, Cough, and Respiratory Complaints

Formulation: Leaf decoction or stem infusion.

Preparation and Use: A decoction of the leaves or stem is prepared and consumed warm to reduce fever, particularly in the dry, hot season when fevers are common. For cough, the stem infusion is taken with honey.

Scientific Validation: The antipyretic activity demonstrated in animal models and the anti-inflammatory effects on respiratory mucosa provide partial validation. The demulcent properties of the mucilaginous stem may soothe throat irritation.

7.5 Regional Ethnomedicinal Applications Summary

India (Ayurveda and Folk Medicine): The plant is classified as kashaya (astringent), tikta (bitter), and ushna (hot) in Ayurveda. It is used primarily for fractures (asthi bhagna), joint disorders (sandhivata), and wounds (vrana). It is considered an asthisandhaniya (bone-joining) herb, a specific category in Ayurvedic pharmacology. In the folk medicine of Rajasthan, Gujarat, and Maharashtra, it is a first-line remedy for fractures in both humans and livestock. The tribal communities of the Western Ghats and the Deccan use the stem paste for snakebites, though this use is not pharmacologically validated.

Pakistan: In the traditional medicine of Punjab and Sindh, the plant is used for bone fractures, joint pain, and as a tonic for weakness.

Sri Lanka: The stem is used in traditional Sinhala medicine for fractures and sprains. The leaves are applied to wounds.

Thailand: Regional folk medicine uses the stem for bone healing and inflammation, a tradition likely transmitted through cultural exchange with India.

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8. Healing Recipes, Teas, Decoctions, and Practical Applications

8.1 Traditional Bone-Setting Paste for Fracture Support

Purpose: To be applied externally over a properly set and splinted fracture to reduce inflammation, provide antimicrobial protection, and deliver osteogenic compounds locally.

Preparation and Use: Harvest a section of mature Cissus vitiginea stem, approximately 20 centimetres long and 2 to 3 centimetres in diameter. Wash thoroughly. Scrape away the outer, fibrous bark with a knife, revealing the pale greenish-white inner tissue. Using a clean mortar and pestle, pound the inner stem tissue into a fine, homogeneous paste. If the paste is too dry, add a few drops of water or fresh aloe vera gel. Some traditional practitioners add a pinch of turmeric powder for its additional anti-inflammatory and antimicrobial properties. The paste is applied in a thick layer (approximately 5 to 10 millimetres) over the fracture site, which must already have been reduced (aligned) and immobilized by a qualified bone-setter or medical professional. The paste is then wrapped with a clean cotton cloth and left to dry and harden, forming a natural cast. The application is renewed every three days, at which time the fracture site is inspected. This is a traditional external application only and must not replace professional medical fracture management.

Scientific Validation: The osteogenic triterpenoids (friedelin, lupeol) and the anti-inflammatory stilbenoids (piceatannol, resveratrol) are released from the paste and absorbed percutaneously. The antimicrobial activity prevents infection at any break in the skin. The drying paste provides mechanical immobilization. The 2025 fracture study supports the pharmacological rationale, though the external paste component specifically has not been tested in isolation. This traditional preparation should be used as an adjuvant to, not a replacement for, conventional orthopedic care.

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8.2 Stem Decoction for Internal Fracture Healing Support

Purpose: To be consumed internally to provide systemic delivery of osteogenic and anti-inflammatory compounds during fracture recovery.

Preparation and Use: Take 5 to 10 grams of dried Cissus vitiginea stem powder (or 15 to 20 grams of fresh, chopped stem). Place in a pot with 400 millilitres of water. Bring to a boil, then reduce heat and simmer until the liquid is reduced by half, to approximately 200 millilitres. Strain the decoction through a fine cloth. Allow to cool to a comfortably warm temperature. Divide into two doses of 100 millilitres each. Consume one dose in the morning on an empty stomach and one dose in the evening, half an hour before a meal. Continue for the duration of fracture healing, typically four to eight weeks depending on the bone and the severity of the fracture. The decoction is bitter and astringent. Honey may be added to improve palatability.

Scientific Validation: The 2025 study demonstrating accelerated callus formation and upregulated osteogenic gene expression used an orally administered methanolic extract. This decoction, while an aqueous preparation that will extract a different profile of compounds (fewer non-polar triterpenoids, more polar phenolics and some stilbenoids), is the traditional internal preparation and is consistent with the validated approach. For optimal extraction of triterpenoids, traditional methods that incorporate a small amount of ghee or oil during decoction (a form of lipophilic extraction) may be more effective, a traditional pharmaceutical insight.

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8.3 Poultice for Inflammatory Joint Pain

Purpose: To provide local anti-inflammatory and analgesic relief for acutely swollen, painful joints in arthritis or after a sprain.

Preparation and Use: Prepare a paste as described in 8.1, using fresh Cissus vitiginea stem or root. Warm the paste gently by placing it in a clean cloth and steaming it briefly, or by mixing it with a small amount of warm sesame oil. Apply the warm paste to the swollen, painful joint (knee, ankle, wrist). Cover with a clean cotton cloth and leave in place for 2 to 4 hours. Repeat twice daily. Wash the skin gently with warm water between applications.

Scientific Validation: The dual COX-2/5-LOX inhibition provides a strong mechanistic basis for the anti-inflammatory effect. The warmth of the poultice enhances local blood flow and the percutaneous absorption of the bioactive compounds. The analgesic activity, demonstrated in animal models, supports pain relief. This is a safe external application for symptomatic relief.

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8.4 Leaf Paste for Minor Wounds and Skin Infections

Purpose: To clean, protect, and promote the healing of minor cuts, scrapes, and superficial skin infections.

Preparation and Use: Gather a handful of fresh, undamaged Cissus vitiginea leaves. Wash them thoroughly with clean water. Crush or pound the leaves into a smooth, green paste. Apply a thin layer of the paste directly to the cleaned wound. Cover with a clean gauze or cloth. Leave in place for 6 to 8 hours, then remove, clean the wound gently, and reapply fresh paste. Discontinue if any signs of irritation or worsening infection appear.

Scientific Validation: The in vitro antimicrobial activity and the astringent action of the leaf tannins support this use. The leaf paste is appropriate for minor, superficial wounds. Deep, heavily contaminated, or infected wounds require professional medical care, and the leaf paste should not delay or replace such care.

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9. Clinical Significance and Evidence Summary

9.1 Evidence Hierarchy by Activity

Bone Healing (Osteogenic Activity): Moderate evidence from in vitro studies and animal models. The 2025 rat tibial defect study provides the most comprehensive validation to date, with histomorphometric, gene expression, and biomechanical endpoints. The mechanism (Runx2 and osteocalcin upregulation, COX-2/5-LOX inhibition) is partially characterized. Human clinical trials are entirely absent. The extensive traditional evidence base across multiple cultures provides strong supportive, though not confirmatory, evidence.

Anti-inflammatory: Moderate evidence. COX-2 and 5-LOX inhibition is demonstrated in multiple in vitro assays with defined IC50 values. The responsible compounds (piceatannol, resveratrol, lupeol) are identified, and their inhibitory mechanisms are characterized. Animal models of inflammation confirm the in vitro findings. Human data are absent.

Antioxidant: Strong evidence in vitro. Multiple assays demonstrate radical-scavenging activity, with total phenolic and flavonoid content correlating with activity. In vivo antioxidant biomarkers have not been studied in humans.

Analgesic: Moderate evidence from animal models. The hot-plate and acetic acid writhing tests demonstrate both central and peripheral analgesic activity. Human data are absent.

Antimicrobial: Moderate evidence in vitro. Activity against common wound pathogens is demonstrated. The clinical relevance of this activity for wound healing has not been tested in controlled trials.

Anti-arthritic and Chondroprotective: Moderate evidence from in vitro studies (chondrocyte cultures, MMP inhibition assays) and animal models (MIA-induced arthritis). The mechanism of MMP/TIMP modulation is well characterized in vitro. Human clinical trials are absent.

Antidiabetic, Hepatoprotective, Anthelmintic, Antipyretic: Preliminary evidence from animal models and in vitro assays. These activities are not the primary traditional uses of the plant and have been less intensively studied.

9.2 Comparison with Cissus quadrangularis

The bone-healing activity of Cissus quadrangularis (hadjod) is more extensively studied than that of C. vitiginea, with multiple animal studies and a few small human clinical trials supporting its efficacy in accelerating fracture healing and reducing bone loss in osteoporosis. C. quadrangularis contains ketosteroids (particularly beta-ecdysone) that are not reported from C. vitiginea and that are believed to be major contributors to its osteogenic activity. C. vitiginea, by contrast, relies more heavily on its triterpenoid and stilbenoid profile. Direct comparative studies of the two species are needed to determine whether C. vitiginea is a pharmacologically equivalent substitute or whether it has distinct advantages (for example, in anti-inflammatory activity due to its stilbenoid content). In the herbal market, C. quadrangularis is the preferred and more expensive species, and C. vitiginea is frequently used as an adulterant or lower-cost alternative. Quality control methods to distinguish the two species in powdered form are needed.

9.3 Safety and Toxicology Summary

No systematic toxicity studies of Cissus vitiginea have been published. Traditional use over centuries suggests a wide margin of safety for the stem and leaf preparations at conventional doses. The fruits are consumed as food, albeit in small quantities due to their astringency. No adverse events have been reported in the animal studies published to date. However, the absence of formal toxicity data, including acute, sub-chronic, and genotoxicity studies, is a significant gap in the evidence base. The presence of oxalate crystals in the plant tissues, common in the Vitaceae, warrants caution in individuals predisposed to kidney stones. The plant's safety during pregnancy and lactation has not been established.

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10. Safety and Toxicology

10.1 Toxicity Profile

Acute Toxicity: No published data exist for C. vitiginea. Extrapolation from the closely related C. quadrangularis, for which the oral LD50 in rodents is greater than 2,000 mg/kg, suggests low acute toxicity. The long history of traditional internal use supports a benign acute toxicity profile at traditional doses.

Sub-chronic and Chronic Toxicity: Not studied. The potential for cumulative effects of stilbenoids, triterpenoids, or oxalates with prolonged high-dose consumption is unknown. Traditional use is typically for weeks to a few months (the duration of fracture healing or an arthritis flare), not for years.

Genotoxicity and Carcinogenicity: Not studied. Resveratrol and other stilbenoids are generally considered non-genotoxic and have shown chemopreventive activity in some contexts, but this cannot be extrapolated to the whole plant extract without specific data.

Renal Safety: The presence of calcium oxalate crystals in Vitaceae tissues raises a theoretical concern for individuals predisposed to oxalate kidney stones. Adequate hydration during treatment is advisable.

10.2 Contraindications and Precautions

Pregnancy and Lactation: Safety has not been established. Traditional bone-setters may use the plant during pregnancy, but in the absence of safety data, it should be avoided during pregnancy and lactation. Some triterpenoids have demonstrated uterine stimulant activity in other plant species.

Known Hypersensitivity: Individuals with known allergy to grapes (Vitis vinifera) or other Vitaceae should exercise caution. Cross-reactivity is plausible but undocumented.

Surgery: The plant's potential effects on bleeding (antiplatelet activity of stilbenoids) and bone metabolism have not been characterized. Discontinuation two weeks before elective surgery is a conservative precaution.

10.3 Potential Drug Interactions

Anticoagulants and Antiplatelet Drugs (Warfarin, Aspirin, Clopidogrel): Stilbenoids, particularly resveratrol, have demonstrated antiplatelet activity in vitro and in some human studies. While the concentrations achieved with traditional C. vitiginea preparations are unknown, a theoretical interaction exists. Patients on anticoagulant therapy should exercise caution and monitor INR if they choose to use the plant.

NSAIDs and Corticosteroids: The plant's own anti-inflammatory activity could theoretically be additive with that of conventional anti-inflammatory drugs. The clinical significance is unknown. Co-administration may increase the risk of gastrointestinal irritation, though the plant's COX/LOX inhibition profile suggests a potentially gastroprotective, rather than gastro-irritant, effect.

Hypoglycemic Agents: If the preliminary antidiabetic activity is confirmed, additive effects with insulin or oral hypoglycemics are possible. Blood glucose monitoring is advised for diabetic patients using the plant.

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11. Quality Control Parameters

11.1 Marker Compounds for Standardisation

For a plant with an emerging pharmacological profile and no established pharmacopoeial monograph, quality control must begin with the identification and quantification of the bioactive markers most relevant to the primary traditional use.

Triterpenoid Fraction: Total triterpenoid content, measured spectrophotometrically or gravimetrically, provides a general quality index. Individual triterpenoids (friedelin, epifriedelanol, lupeol, beta-sitosterol) can be quantified by HPLC-DAD or GC-MS after derivatization. Friedelin is a suitable single marker compound for standardisation, being characteristic of the genus and present in pharmacologically relevant concentrations.

Stilbenoid Content: Resveratrol and piceatannol should be quantified by HPLC-DAD or LC-MS/MS. Piceatannol, with its potent dual COX/LOX inhibitory activity, is a functionally relevant marker for anti-inflammatory quality.

Total Phenolic and Flavonoid Content: The Folin-Ciocalteu and aluminium chloride colorimetric methods provide simple, low-cost quality parameters that correlate with antioxidant activity.

11.2 Recommended Analytical Methods

HPLC-DAD with a C18 reversed-phase column is suitable for the simultaneous quantification of resveratrol, piceatannol, and the major phenolic acids. A gradient elution of water:acetonitrile (both with 0.1 percent formic acid) provides adequate separation. For triterpenoids, which lack strong chromophores, HPLC with evaporative light scattering detection (ELSD) or GC-MS after silylation are preferred. HPTLC fingerprinting provides a rapid, visual, and cost-effective method for species authentication and for distinguishing C. vitiginea from C. quadrangularis and other substitutes. DNA barcoding using the chloroplast markers rbcL and matK is a definitive method for species identification of powdered or processed material.

11.3 Suggested Specifications

For dried stem powder intended for medicinal use, moisture content should be less than 10 percent, and total ash should be less than 12 percent. Acid-insoluble ash should be less than 2 percent. Total triterpenoid content, expressed as friedelin equivalents, should be not less than 0.5 percent by weight. Total stilbenoid content, expressed as resveratrol equivalents, should be not less than 0.1 percent. Heavy metal concentrations (lead, cadmium, mercury, arsenic) must comply with national pharmacopoeial limits. Microbial load (total aerobic count, yeast and mould, absence of E. coli and Salmonella) must meet food safety standards if the product is for internal consumption.

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12. Cultivation and Sustainability

12.1 Growth Requirements

Climate: Cissus vitiginea is adapted to tropical and subtropical dry climates. It thrives in regions with a distinct dry season of 6 to 8 months and annual rainfall of 500 to 1,500 millimetres. It is highly drought-tolerant, surviving the dry season by shedding its leaves and photosynthesizing through its green bark.

Soil: It tolerates a wide range of well-drained soils, including rocky, sandy, and lateritic substrates. It is not tolerant of waterlogged conditions. It often colonizes stony outcrops, hedgerows, and forest margins, demonstrating a preference for free-draining, base-rich soils.

Propagation: The plant is propagated from seed and from stem cuttings. Seeds have a hard testa and benefit from scarification (nicking or abrading the seed coat) to break dormancy. Stem cuttings, 20 to 30 centimetres long with 2 to 3 nodes, root readily during the rainy season when planted directly into moist soil. This is the preferred method for cultivation, as it is faster and more reliable than seed propagation and preserves the desirable traits of the parent plant.

12.2 Harvesting and Post-Harvest Processing

The stem is harvested during the dry season, when the concentration of secondary metabolites is presumed to be highest. Stems of 2 to 4 centimetres diameter and at least one year of age are selected. The stem is cut into sections, the outer bark is stripped away, and the inner tissue is sliced and dried in the sun or in a low-temperature dryer (below 50 degrees Celsius) to preserve the heat-sensitive stilbenoids. Dried stem pieces are stored in airtight containers protected from light and moisture.

12.3 Sustainability and Conservation

The primary sustainability concern with Cissus vitiginea is the harvesting of roots, which destroys the plant. The stem, when harvested sustainably by cutting above ground level and leaving the rootstock to regenerate, is a renewable resource. However, increasing commercial demand for bone-healing herbs, combined with confusion with the more expensive C. quadrangularis, is placing pressure on wild populations. The development of cultivation protocols, the encouragement of stem over root harvesting, and the establishment of sustainable wild-harvesting quotas are needed. The plant's absence from major germplasm collections is a conservation gap.

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13. Species and Varietal Comparison

Cissus vitiginea vs. Cissus quadrangularis (Hadjod, Asthisamharaka)

These two species are the most important medicinal members of the genus in the Indian subcontinent and are frequently confused or substituted. Their comparison is essential for quality control, clinical use, and conservation.

Morphology: C. quadrangularis is unmistakable. Its stem is fleshy, quadrangular (four-angled), with distinct constrictions at the nodes. It is a succulent climber, often leafless, and its appearance is radically different from the woody, terete stem of C. vitiginea. In the dried and powdered form, however, the two are difficult to distinguish visually. Microscopic examination of the powder reveals characteristic calcium oxalate crystals and vascular bundle arrangement that differ between the species. C. vitiginea has broad, simple, cordate leaves; C. quadrangularis has small, trilobed leaves that are soon deciduous.

Phytochemistry: C. quadrangularis is characterized by the presence of ketosteroids (beta-ecdysone, 20-hydroxyecdysone) that are not reported from C. vitiginea. These phytoecdysteroids have osteogenic, anabolic, and adaptogenic activities. C. vitiginea appears to have a higher stilbenoid content, particularly piceatannol, giving it a potentially stronger anti-inflammatory profile. Both species contain triterpenoids (friedelin, lupeol, beta-sitosterol), flavonoids, and phenolic acids.

Pharmacology: Both are used traditionally as bone-setters and for arthritis. The clinical evidence base for C. quadrangularis is more developed, with small human trials supporting its efficacy in fracture healing and in reducing bone loss in postmenopausal osteoporosis. C. vitiginea has comparable preclinical evidence for bone healing but lacks human data. The choice between them in the herbal market is often driven by cost and availability rather than by differentiated clinical indications.

Conservation Status: C. quadrangularis is more widely cultivated and less threatened by wild harvesting. C. vitiginea is predominantly wild-harvested and faces greater conservation pressure, particularly in regions where root harvesting is practiced.

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14. Research Gaps and Future Directions

14.1 Critical Research Gaps

Human Clinical Trials: The single most significant gap is the complete absence of human clinical data for any of the traditional indications. A randomized, double-blind, placebo-controlled trial of C. vitiginea stem extract as an adjuvant to standard fracture management, with radiographic, functional, and biochemical endpoints, would be the definitive study. A trial in knee osteoarthritis, with pain, function, and cartilage biomarkers as endpoints, is a second priority.

Systematic Toxicity Studies: Acute, sub-chronic, and chronic toxicity studies in two animal species, genotoxicity (Ames test, micronucleus assay), and reproductive toxicity are required before the plant can be recommended for clinical use beyond the traditional context.

Pharmacokinetics: The absorption, distribution, metabolism, and excretion of the key triterpenoids and stilbenoids from C. vitiginea are unknown. Bioavailability studies are essential for rational dose determination and for understanding the relationship between in vitro bioactivity and in vivo efficacy.

Comparative Pharmacology with C. quadrangularis: A head-to-head comparison of the two species in standardized preclinical models of fracture healing and arthritis would clarify whether they are interchangeable or have distinct therapeutic profiles.

Sustainable Cultivation: Agronomic protocols for the commercial cultivation of C. vitiginea, including optimal planting density, irrigation, fertilization, and harvest age, do not exist. Developing these protocols is a prerequisite for shifting supply from wild harvesting to cultivation.

14.2 Future Research Priorities

Isolation and Characterization of Osteogenic Compounds: Bioassay-guided fractionation using the Runx2 reporter gene assay or osteoblast mineralization assay to identify the most potent osteogenic compounds in the stem extract is a logical next step. These compounds could serve as lead molecules for drug development or as high-value standardisation markers.

Stilbenoid Profiling: A comprehensive LC-MS/MS profiling of the stilbenoid content of C. vitiginea, including the identification of resveratrol oligomers (viniferins) that may have enhanced bioactivity, is warranted. This could reveal novel compounds with therapeutic potential.

Formulation Development: The development of standardized extracts (aqueous, hydroalcoholic, methanolic) with defined concentrations of marker compounds, and their incorporation into topical (gel, cream, patch) and oral (tablet, capsule) formulations, is a necessary step toward clinical testing and commercialization.

Adulterant Detection: The development of a validated HPTLC or DNA barcoding method for distinguishing C. vitiginea from C. quadrangularis and other Cissus species in powdered form would address a significant quality control gap in the herbal market.

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15. Commercial Applications

15.1 Herbal Medicine and Nutraceutical Industry

Cissus vitiginea is commercially available in the Indian herbal market, primarily as dried stem pieces and stem powder, and as an ingredient in multi-herb formulations for bone health (asthi sandhaniya yogas) and arthritis. It is sold as a lower-cost alternative or substitute for Cissus quadrangularis. Standardized extracts for the nutraceutical market, with defined triterpenoid and stilbenoid content, are a significant commercial opportunity, particularly given the growing global market for natural bone health products driven by the aging population and the increasing prevalence of osteoporosis. A standardized extract positioned as a dual-action bone health ingredient (promoting bone formation and reducing inflammation) could capture market share in the joint health and sports medicine sectors.

15.2 Topical and Cosmeceutical Applications

The anti-inflammatory and wound-healing properties of the stem and leaf extracts lend themselves to the development of topical formulations. Gels or creams containing standardized C. vitiginea extract for the relief of joint and muscle pain, sports injuries, and inflammatory skin conditions are plausible products. The antioxidant stilbenoids have anti-aging potential, and the extract could be explored as an ingredient in cosmeceutical formulations for photoaging and skin protection, following the trajectory of resveratrol from grape.

15.3 Veterinary Medicine

In rural India, C. vitiginea is widely used by traditional livestock healers for fractures and joint injuries in cattle, buffalo, and working equines. A standardized, low-cost veterinary formulation for fracture support and arthritis in large animals has a clear market in regions where traditional veterinary medicine remains the primary accessible care.

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16. Related Plants for Further Study

Cissus quadrangularis (Hadjod, Asthisamharaka): The most closely related medicinal species, with a more developed clinical evidence base for bone healing and osteoporosis. Comparative studies are the highest research priority for understanding the therapeutic niche of C. vitiginea.

Cissus verticillata (Insulin Plant): A Neotropical species with a distinct medicinal profile focused on diabetes and metabolic syndrome. Its pharmacology, rich in stilbenoids and flavonoids, provides a comparative counterpoint to the bone-focused pharmacology of the Asian species.

Cissus sicyoides (syn. C. verticillata): Used in Brazilian and Caribbean traditional medicine for diabetes, inflammation, and epilepsy. Its traditional use as an anticonvulsant is a unique indication within the genus.

Vitis vinifera (Grape): The genomic and phytochemical model for the Vitaceae. Resveratrol, first isolated from grapevine, is the benchmark against which Cissus stilbenoids are measured. The vast literature on resveratrol's pharmacology provides hypotheses and methodologies for investigating Cissus.

Parthenocissus tricuspidata (Boston Ivy): A temperate Vitaceae with traditional use in East Asian medicine. Its stilbenoid profile and anti-inflammatory activity have been investigated, providing a Northern Hemisphere comparison to the tropical Cissus.

Ampelocissus latifolia and Ampelocissus tomentosa: Indian Vitaceae with edible fruits and traditional medicinal uses that overlap partially with Cissus vitiginea. Their phytochemistry and pharmacology are understudied relative to Cissus.

Leea indica and Leea macrophylla: The phylogenetically basal members of the Vitaceae, used in Ayurveda for wounds, diabetes, and cardiac conditions. Their chemistry (which includes unique anthocyanidins and triterpenoids) and pharmacology represent the broader metabolic capacity of the family.

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17. Reference Literature

Primary Research

Accelerated fracture healing by Cissus vitiginea stem extract through Runx2-mediated osteoblast differentiation in a rat tibial defect model (2025) reports histomorphometric, gene expression, and biomechanical evidence of accelerated and enhanced fracture healing, with molecular characterization of the osteogenic mechanism.

Dual COX-2/5-LOX inhibition by Cissus vitiginea extract and isolated stilbenoids: mechanistic basis for traditional anti-arthritic use (2025) provides enzyme kinetics, molecular docking data, and in vitro chondroprotection assay results for the stem extract and purified piceatannol.

Piceatannol and resveratrol from Cissus species: chemistry, biological activity, and therapeutic potential (2023) in Phytochemistry Reviews provides a comprehensive overview of stilbenoids in the genus, including isolation methodology and pharmacological data.

Cissus quadrangularis: a comprehensive review of its phytochemistry, pharmacology, and clinical evidence (2022) in the Journal of Ethnopharmacology serves as the benchmark review for the genus and a comparative reference for C. vitiginea.

Traditional bone-setting practices of the Bhil and Meena tribes of Rajasthan: an ethnomedicinal survey (2018) in the Indian Journal of Traditional Knowledge documents the use of C. vitiginea by traditional practitioners, including preparation methods and clinical observations.

Key Monographs and Floras

Flora of India, Volumes 5 and 9 (2000, 2019) by the Botanical Survey of India provides the authoritative botanical description, distribution maps, and taxonomic notes for Cissus vitiginea and related species.

Indian Medicinal Plants: An Illustrated Dictionary (2007) by C.P. Khare includes entries for Cissus vitiginea and C. quadrangularis with traditional uses and Ayurvedic classifications.

The Ayurvedic Pharmacopoeia of India, Part I, Volume IV (2004) includes the monograph for Cissus quadrangularis (Asthisamharaka), which provides the quality standards that should be adapted for C. vitiginea.

Database on Medicinal Plants Used in Ayurveda, Volume 3 (2001) by the Central Council for Research in Ayurveda and Siddha provides traditional formulations and indications for Cissus species.

Vitaceae in Flora of Thailand (2010) provides the regional botanical context for the species in Southeast Asia.

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18. Disclaimer

Cissus vitiginea is a traditional medicinal plant. Its use for fracture healing, arthritis, and other conditions is supported by centuries of traditional practice and by preclinical scientific evidence, but it has not been evaluated in human clinical trials. It is not an approved drug for any indication.

This information is for educational and academic purposes only and is not a substitute for professional medical advice, diagnosis, or treatment.

Fractures and joint injuries require professional medical assessment and management. Cissus vitiginea preparations should only be used as an adjuvant to, not a replacement for, conventional orthopedic care under the supervision of a qualified healthcare practitioner.

The safety of C. vitiginea during pregnancy, lactation, and in children has not been established. Use in these populations is not recommended.

Individuals with known allergy to grapes or other Vitaceae, individuals with a history of kidney stones, and individuals on anticoagulant or antiplatelet medications should exercise caution and consult a qualified healthcare practitioner before use.

Do not discontinue or alter prescribed medications without consulting your doctor.

Ensure proper botanical identification of the plant material. Confusion with other Cissus species is possible, and the pharmacological profiles may differ.

Always consult a qualified healthcare practitioner before using any plant for medicinal purposes.

PREHEALING

Cissus vitiginea (Vitaceae) - Wild grapes

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