Paederia foetida

Paederia foetida: A Comprehensive Reference

1. Identity, Taxonomy, and Natural Source

Paederia foetida Linn. is a widespread plant of the Rubiaceae family distributed in temperate and tropical Asia. It is known by numerous common names, including Chinese Fever Vine (Bengali: Gandhavadulia, Gondabadali, Gondhal; English: King's Tonic, Skunkvine, Stinkvine). The plant is locally known as "Gandhavadulia" or "GandhaPrasarini" in South Asia, and its English name is "skunkvine." Its Chinese local name is Jishiteng, and it is described as a perennial vine plant of the Rubiaceae family that has been utilized for both medicinal and edible purposes in China for over three centuries.

The plant has a distinct characteristic of emitting a strong and sulfurous odor on crushing and bruising of its leaves or stems. It is a climbing plant widely distributed in Bangladesh, India, Japan, Malaysia, Myanmar, Nepal, Thailand, Vietnam, Cambodia, and China. Paederia foetida Linn., also known as Paederia scandens, is the lectotype species of the Paederia genus.

Plant Parts Used and Common Preparations

Phytochemical investigations of P. foetida leaves suggest the presence of glycosides, flavonoids, alkaloids, carbohydrates, amino acids, and volatile oils. All parts of the plant — leaves, stems, roots, aerial parts, and twigs — have been subjected to pharmacological investigation. Common preparations reported in the literature include:

• Aqueous (water) extracts — prepared by decoction or infusion of leaves or aerial parts.
• Ethanolic and methanolic extracts — standardized laboratory preparations most commonly used in pharmacological assays.
• Hydroalcoholic (e.g., 70% ethanol) extracts — used in both traditional preparations and formal toxicity studies.
• Volatile/essential oil — obtained from aerial parts by steam distillation.
• The leaves are used as a culinary spice in traditional cooking in North Eastern and Eastern India; in Hainanese cuisine, the leaves are ground into flour and mixed with rice to form noodles used in a sweet soup.

2. Traditional and Historical Use

The plant has a long history of usage in Chinese, Ayurvedic, and other traditional systems of medicine for numerous ailments. P. foetida, which grows mainly in China, Bangladesh, India, and Mauritius, has been used in folk medicine for the treatment of inflammation, piles, and diarrhea.

South Asian (Ayurvedic and Ethnobotanical) Traditions

In India, it has been used for rheumatism and stiffness of the joints; a poultice of leaves has been applied to the abdomen to relieve distention and flatulence; the juice of the root has been used for piles, liver, and spleen ailments. In Ayurveda, it has been employed for asthma, bowel problems, diarrhea, diabetes, rheumatism, and seminal weakness.

Among the ethnic tribes of northeastern India, Paederia foetida has been used as both food and medicine, with many of its therapeutic properties relating to the gastrointestinal system. Different tribal communities of North East to Southern India use the plant as a vegetable and to treat different stomach disorders like diarrhoea and dysentery, stomach swelling, to clean the stomach, gastritis, loose motion, indigestion, and abdominal pain.

The plant has been traditionally used to treat sores, rheumatic joint conditions, night blindness, digestive problems, and toothache. In addition, P. foetida is considered good for women after childbirth. It was used traditionally to reduce bloating and was used by women after giving birth.

Chinese Traditional Medicine

P. foetida has been widely used in Chinese traditional medicine (CTM) for the treatment of dyspepsia, jaundice, pains, diarrhea, and other conditions. In China, it has been utilized for both medicinal and edible purposes for over three centuries.

Broader Ethnomedicinal Scope

The plant has been used as a treatment for ailments including hepatic disorders, rheumatoid arthritis, constipation, diabetes, coughs, asthma, itches, wounds, stomachache, diarrhoea, dysentery, pain, typhoid, pneumonia, toothache, cancer, flatulency, body ache, and bone fractures. It has long been used as a traditional medicine in subtropical countries for the treatment of rheumatism, diarrhoea, inflammation, piles, snake bites, toothaches, and a variety of other ailments.

3. Phytochemistry: Key Constituents and Active Compounds

A total of 217 phytoconstituents comprising glycosides, anthraquinones, phenolic derivatives, terpenoids, phytosterols, and other miscellaneous compounds have been identified in this species. A 2026 review by Tian et al. in European Food Research and Technology identified 208 phytochemical constituents including volatile oils, phenolic compounds, terpenoids and their derivatives, and fatty acids.

Iridoid Glycosides (Primary Bioactive Class)

Among the various types of isolated compounds, iridoid glycosides are the major type of phytoconstituents of P. foetida. In 1969, four new iridoid glycosides — paederoside, paederosidic acid, scandoside, and deacetylasperuloside — along with asperuloside were isolated from fresh leaves and stems of P. foetida using a continuous counter-current extraction method. The aerial parts of the plant contain iridoid glucosides including asperuloside, scandoside, and paederoside.

The four iridoid glycosides — paederosidic acid, paederoside, paederosidic acid methyl ester, and asperuloside — are considered to be the main bioactive constituents. Paederoside B, an iridoid glucoside containing sulfur, has been isolated from the stems of P. foetida.

Other Phytochemical Classes

Phytochemical investigations have reported that Paederia foetida contains paederolone, paederone, β-sitosterol, paederoside, asperuloside, and their related glucosides. The leaves of the plant are also rich in carotene, vitamin C, keto-alcohol, and alkaloid. P. foetida also contains friedelin, campesterol, ursolic acid, hentriacontane, hentriacontanol, ceryl alcohol, palmitic acid, and methyl mercaptan. Additional constituents include ellagic acid, epifriedelinol, terpenoids, alkaloids paederine (α-paederine and β-paederine), volatile compounds, and an essential oil.

The chloroform extract of P. foetida has afforded scopoletin, stigmasterol, γ-sitosterol, and ergost-5-en-3-ol. Scopoletin was isolated from this species for the first time in one comparative study. Eighteen flavonol derivatives have been detected in P. foetida, predominantly occurring as glycosides.

Quantitative phytochemical analysis of the plant indicates the presence of 36 important chemical constituents including methyl-mercaptan, phenolic compounds, a high percentage of minerals, ursolic acid, β-sitosterol, oleanolic acid, and arachidic acid.

4. Mechanisms of Action

Anti-inflammatory Pathway

Although P. foetida has been traditionally used as an anti-inflammatory medicinal plant, its molecular mechanisms of action were poorly understood until computational studies examined the interactions of its phytochemicals with the NF-κB p65 protein. Molecular docking results revealed that several compounds exhibited favorable binding energies with key amino acid residues of NF-κB p65, and among the tested compounds, quercetin and asperuloside demonstrated strong binding affinity and multiple hydrogen bonds within the transcriptionally active region of NF-κB p65. This in silico evidence — while preliminary — suggests a plausible mechanism whereby P. foetida constituents suppress pro-inflammatory gene expression by inhibiting the NF-κB transcriptional pathway.

Antidiabetic Mechanisms

Studies have evaluated the enzymatic inhibition activity of P. foetida twig extracts, testing three different extracts for their α-amylase and α-glucosidase inhibition potential. The chloroform extract exhibited α-amylase and α-glucosidase inhibition activity (IC₅₀ = 14.83 and 257.2 µg/mL, respectively), and scopoletin from both locations had IC₅₀ values of 0.052 and 0.057 µM for α-amylase and α-glucosidase inhibition, respectively.

Sedative / Anticonvulsant Mechanisms

Paederosidic acid isolated from the whole plant showed significant anticonvulsant and sedative effects in animal models; maximum electroshock and pentylenetetrazole-induced seizures were used to assess anticonvulsant activity, while pentobarbital sodium-induced sleeping time and locomotor activity tests assessed sedative effect. It also lowered glutamic acid and elevated gamma-aminobutyric acid (GABA) levels in the brain, and the expression of glutamic acid decarboxylase 65 (GAD 65) was up-regulated in the test groups.

Gastroprotective Mechanisms

The traditional claim of P. foetida as a gastroprotective agent has been supported by experimental observations; the gastroprotective activity may be mediated by Nrf2-mediated antioxidant and anti-secretory effects. The roots of Paederia foetida are said to have anti-ulcer properties, possibly attributable to the suppression of H₂ receptors, which inhibit gastric acid release.

Antinociceptive Mechanisms

A petroleum ether fraction of a methanol extract of P. foetida at doses of 20, 40, and 80 mg/kg showed anti-nociceptive activity in mice against both chemical nociception and thermal nociception; the petroleum ether fraction produced anti-nociception possibly related to glibenclamide-sensitive K⁺-ATP channels.

Antioxidant Mechanisms

The extract of Paederia foetida contains antioxidant compounds that can scavenge free radicals such as DPPH; phenolic compounds protect various organs from damage by scavenging free radicals. Antihyperlipidemic activity has been attributed to possible lowering of lipid profile levels and decreasing the intercalated disc space in the heart, while antioxidant activity has been attributed to inhibition of lipid peroxidation and increases in SOD, GPx, and CAT enzyme activities.

Urate-Lowering Mechanisms

Computational docking results have demonstrated binding interactions between three structurally distinct iridoid glycosides and key urate-regulating proteins (URAT1, GLUT9, and ABCG2). These in silico findings suggest potential mechanisms by which the iridoid glycosides of P. foetida may reduce serum uric acid levels, although these mechanisms require further in vivo and human validation.

5. Scientific Evidence by Area of Use

Note on evidence quality: The substantial majority of available evidence for Paederia foetida is derived from in vitro cell assays, animal models (primarily rodents), and computational/molecular docking studies. As of 2026, no large-scale randomized controlled trials in humans have been published for this plant. Evidence is therefore characterized as preliminary to moderate across all areas.

5.1 Gastrointestinal System — Antidiarrheal Activity

Although P. foetida is used as a remedy for diarrhoea and dysentery in Asia, formal antidiarrheal investigation has utilized a 90% ethanol extract in castor oil– and magnesium sulphate–induced diarrhea models in mice; the extract significantly increased the latent period of diarrhoea in both models, and the purging index value was lowered within 1 hour of the study at doses of 100, 250, and 500 mg/kg. The effect continued up to a 6-hour period only at 500 mg/kg, and the plant notably reduced the purging index value in a dose-dependent manner in magnesium sulphate-induced diarrhoea; P. foetida in general reduced gastrointestinal motility. The results suggest that Paederia foetida showed antidiarrheal activity by inhibiting intestinal motility and justify its use in traditional medicine.

A more recent in vivo study tested the plant in a rat model of enteropathogenic Escherichia coli–induced diarrhea. The 400 mg/kg BW dose demonstrated the most consistent antidiarrheal effects across evaluated parameters. Evidence level: Animal/preclinical only. No human clinical trials are available.

5.2 Gastrointestinal System — Gastroprotective / Anti-ulcer Activity

The methanol extract of P. foetida leaves at two dose levels was investigated for gastroprotective potential using indomethacin-pylorus ligation, alcohol-induced, and water immersion stress–induced models in rats; the extract at 100 mg/kg and 200 mg/kg body weight showed 72% and 78% ulcer protection, respectively, when compared to negative control, whereas the reference drug showed 82% protection in the indomethacin-pylorus ligation model. The extract also showed protective effect against 70% ethanol– and stress-induced gastric ulcer models. About 84% protection, compared to cimetidine (85%), was seen in western blot analysis of stomach tissue from pylorus-ligated rats. Evidence level: Preclinical (animal models) only.

5.3 Anti-inflammatory and Analgesic / Antinociceptive Activity

Phytochemical studies have revealed the presence of iridoids, flavonoids, volatile oil, and other metabolites, which possess versatile bioactivities including antinociceptive and anti-inflammatory activities.

The hexane and methanol extracts of P. foetida at a dose of 300 mg/kg body weight showed significant antinociceptive activity with 37.42% and 25.18% inhibition in the number of writhing, respectively. In a study assessing analgesic and neuropharmacological potential of aqueous, ethanol, and ethyl acetate extracts of the plant leaf at a dose of 400 mg/kg body weight, using acetic acid–induced writhing and formalin-induced persistent pain tests, the results showed that the ethanolic extracts significantly inhibited the nociceptive response in both tests, while the other two extracts showed mild response. Evidence level: Animal models only; no human trials.

5.4 Antidiabetic and Antihyperlipidemic Activity

There is evidence that reactive oxygen species (ROS), which are capable of oxidizing cellular proteins, nucleic acids, and lipids, increase in patients with diabetes, and that the onset of diabetes is closely associated with oxidative stress mainly through oxidation, nonenzymatic protein glycation, and oxidative degradation of glycated proteins.

In vitro enzymatic studies show promising results: the chloroform extract exhibited α-amylase and α-glucosidase inhibition, and scopoletin had IC₅₀ values of 0.052 and 0.057 µM for inhibition of these starch-digesting enzymes, respectively. GC-MS metabolomics revealed the presence of 12 bioactive compounds including dl-α-tocopherol, n-hexadecanoic acid, stigmasterol, and α-monostearin as putative antidiabetic metabolites.

In streptozotocin-induced diabetic rats, the leaf extract of P. foetida was reported to show antihyperglycemic activity through possible systematic effects involving both pancreatic and extra-pancreatic mechanisms. Evidence level: In vitro and animal model studies only; no human trials.

5.5 Antitussive Activity

The antitussive (anti-cough) activity of P. foetida has been evaluated in a non-rodent model: an ethanolic extract was tested in non-anesthetized cats (Nosáľová et al., 2007, Acta Veterinaria Brno, 76: 27–33). The plant has been documented to possess antitussive activity. Evidence level: Preclinical animal study; no human clinical data.

5.6 Hepatoprotective Activity

Plant extract has been shown to exhibit ameliorative effects on hepatotoxin-induced liver damage in the Sprague Dawley rat model. Additional research reveals that it has moderate hepatoprotective activity based on its therapeutic effect against liver disorders. Related iridoid glycosides from the Paederia genus have been reported to exert hepatoprotective effects by regulating nitric oxide synthase. Evidence level: Preclinical (animal) studies only; no human trials.

5.7 Antihyperuricemic and Renoprotective Activity

The urate-lowering effects of three iridoid glycosides (paederosidic acid, paederosidic acid methyl ester, and paederoside) isolated from Paederia foetida and their protection against hyperuricemia-induced kidney injury were investigated in a rat model; a hyperuricemia rat model was established using intraperitoneal potassium oxonate and intragastric adenine for 2 weeks, and rats in the pharmaceutical intervention groups received corresponding drug treatments at 40 mg/kg/day for 7 days. The results showed that the three compounds reduced serum urate, creatinine, and blood urea nitrogen levels, and urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Evidence level: Animal models and molecular docking; no human trials.

5.8 Sedative and Anxiolytic Activity

Billah et al. (2015) used hole cross, open field, and elevated plus maze tests in mice to investigate the sedative-anxiolytic effect of water, ethanol, and ethyl acetate extracts of P. foetida leaves at 400 mg/kg; the aqueous extract showed a slight sedative effect, whilst the other two extracts showed little sedative and anxiolytic properties. Asperuloside, a naturally occurring iridoid glycoside derived from P. foetida, has demonstrated promise as a neuroprotective agent by modulating key signaling pathways, including restoring mitochondrial function and promoting neuronal survival. Evidence level: Preliminary animal data only.

5.9 Antimicrobial Activity

Extracts, essential oils, and compounds isolated from P. foetida exhibit broad spectrum biological activities including antimicrobial activity. These findings are based on in vitro assays measuring inhibitory activity against various pathogen strains. Evidence level: In vitro only.

5.10 Anthelmintic Activity

The plant has been found to exhibit anthelmintic activity. Early observations of effects on gastrointestinal helminths in bovine animals were reported by Roychoudhury et al. in 1970. Evidence level: Preliminary animal/preclinical evidence; no robust human trials.

5.11 Anticancer / Cytotoxic Activity

Paederoside, an iridoid glycoside isolated from the Paederia genus, showed significant inhibitory effects on Epstein-Barr virus early antigen activation by tumor promoters, with an inhibition rate of 89.5% (higher than genipin at 62.1%), suggesting it could be a potential cancer chemopreventive candidate; however, further work is needed regarding its anti-tumor mechanism of action in vivo. Growing evidence shows many of its active constituents to be effective in cancer and inflammatory diseases. Evidence level: In vitro and preliminary animal data; no human trials.

6. Body Systems and Health Areas of Association

The extracts, essential oils, and compounds isolated from P. foetida exhibit a broad spectrum of biological and pharmacological activities including analgesic, anti-inflammatory, anti-arthritic, antimicrobial, hepatoprotective, anti-diabetic, antioxidant, gastrointestinal, antihyperuricemic, anthelmintic, cytotoxic, renoprotective, cardiotonic, wound healing, sedative, anxiolytic, and anticonvulsant activities. The following body systems are most prominently associated with this plant in the scientific literature:

• Gastrointestinal system: diarrhea, dysentery, gastric ulcer, dyspepsia, flatulence, gastroprotection, intestinal motility.
• Hepatorenal system: hepatoprotection against toxin-induced liver damage; renoprotection and uric acid excretion in hyperuricemia.
• Musculoskeletal/Inflammatory system: rheumatism, arthritis, joint pain, anti-inflammatory and analgesic effects.
• Metabolic system: blood glucose modulation, lipid profile modulation, α-amylase and α-glucosidase inhibition.
• Respiratory system: antitussive (cough suppression).
• Central nervous system: sedative, anxiolytic, anticonvulsant properties via GABAergic pathways.
• Immune/Antimicrobial: antibacterial, anthelmintic, antifungal activities.
• Oncology (preliminary): cytotoxic and chemopreventive potential in vitro.

7. Dosage Forms and Dosages Reported in Studies

No standardized human dosage for Paederia foetida supplements has been established, and no dosage has been approved or validated by regulatory authorities such as the FDA, EMA, or WHO. The following dosages are reported only as used in the cited preclinical studies:

• Antidiarrheal activity in mice using 90% ethanol extract: 100, 250, and 500 mg/kg body weight (administered orally in castor oil– and magnesium sulphate–induced diarrhea models).
• Antidiarrheal effects in an EPEC rat model: 400 mg/kg body weight demonstrated the most consistent effects.
• Gastroprotective activity in rats: 100 mg/kg and 200 mg/kg body weight of methanol extract.
• Antinociceptive activity in mice: hexane and methanol extracts at 300 mg/kg body weight.
• Anticonvulsant and sedative effects in mice and rats: paederosidic acid at 5, 10, 20, and 40 mg/kg intraperitoneally.
• Urate-lowering effect in rats: iridoid glycosides at 40 mg/kg/day for 7 days.
• Anti-nociceptive activity in mice: petroleum ether fraction of methanol extract at 20, 40, and 80 mg/kg.
• Subchronic oral toxicity study (OECD guideline, Swiss albino mice): hydroalcoholic extract at doses of 100, 300, and 1000 mg/kg body weight.
• Acute and sub-acute toxicity study in Wistar albino rats: methanol extract at acute doses of 500, 1000, and 2000 mg/kg (14 days) and sub-acute doses of 500, 1000, and 1500 mg/kg (28 days).
• Acute oral toxicity evaluated using OECD Guideline 423 at doses of 400, 2,000, and 10,000 mg/kg body weight in rats.

8. Safety Considerations

Preclinical Toxicology Data

In a 2025 toxicological study, the methanol extract (PFME) exhibited a favorable safety profile, with no adverse effects detected at doses up to 2000 mg/kg in acute toxicity studies and 1000 mg/kg/day in sub-acute toxicity studies, thereby establishing this dosage as the No-Observed-Adverse-Effect Level (NOAEL).

Because the toxicity of a plant following repeated exposure is of higher clinical significance, a subchronic toxicity study was conducted; a sub-chronic oral toxicity study of the hydroalcoholic leaf extract (HAPF) was done according to the OECD guideline. This study was conducted as an in vivo safety assessment according to OECD guideline 408.

Although the pharmacological potential of P. foetida has been widely reported, data on systemic safety, particularly after acute and subchronic oral exposure, are still relatively limited and fragmented. Some toxicological studies indicate good tolerability at low to moderate doses, but biochemical and histopathological alterations begin to appear at higher doses or repeated exposure. This gap becomes even more relevant in the modern context, where herbal extracts are often consumed in concentrated forms as supplements or phytopharmaceutical preparations, which may result in supratherapeutic exposures compared to traditional uses.

Hepatic Considerations

The liver is a primary target organ in oral toxicity studies because of its central role in xenobiotic metabolism and detoxification. Paederia foetida is a medicinal plant widely used traditionally for digestive disorders, inflammatory conditions, and complaints associated with liver function. While lower doses appear hepatoprotective, higher doses require careful monitoring, as biochemical and histopathological alterations begin to appear at higher doses or with repeated exposure.

Absence of Human Clinical Trial Safety Data

Paederia foetida has long been utilized in traditional medicine, necessitating comprehensive safety assessments and precise dosage recommendations to avert potential adverse effects in human use. No randomized controlled human trials with formal safety monitoring have been published for this plant as of the date of this article. All existing safety data are from animal models and cannot be directly extrapolated to humans.

Potential Drug Interactions

Available scientific references reveal that the biological properties of P. foetida have been evaluated by modern pharmacological studies; however, bioguided isolation of active constituents responsible for the medical uses, as well as study of their structure–activity relationship and mode of actions, is urgently needed. Based on known pharmacological activities — hypoglycemic, anticoagulant/thrombolytic, and sedative — there is a theoretical basis for interactions with antidiabetic agents, anticoagulants, and CNS-active medications, but no human pharmacokinetic or drug interaction studies are available to characterize these.

Pharmacokinetics of Key Constituents

The pharmacokinetics and action mechanisms of the iridoid glycosides remain poorly characterized; however, a method of simultaneous determination of four iridoid glycoside components in rat plasma by LC-MS/MS has been established. A total of seven compounds including three iridoid glucosides and four of their metabolites were identified in rat urine samples, and six compounds including four iridoid glucosides and two of their metabolites were identified in rat serum samples after administration. No human pharmacokinetic data are available.

9. Research Gaps and Current Status

Available scientific references reveal that the biological properties of Paederia species have been evaluated by modern pharmacological studies; however, bioguided isolation of active constituents responsible for the medical uses, as well as study of their structure–activity relationship and mode of actions, is urgently needed. P. foetida is promising as a remedy for lifestyle-related conditions, especially treatment of ulcers; its utility highlights the need for proper evaluation of tribal plants as medicines, and the species could be considered for development of new drugs.

The plant's first comprehensive evaluation of its potential applications in functional food development provides a basis for future research and utilization in nutraceutical industries. The body of evidence remains almost entirely preclinical, and progression to human clinical trials is required before any efficacy claims can be validated for health supplement use.

References

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