Tylophora (Tylophora indica): A Comprehensive Reference
1. Identity and Botanical Profile
Accepted Name, Synonyms, and Taxonomy
Tylophora indica (Burm. f.) Merr., commonly known as ananthamool, is a climbing perennial plant widely used in Indian traditional medicine. The genus Tylophora (family Apocynaceae) consists of 63 accepted species distributed across Sri Lanka, Burma, Singapore, Nepal, Laos, Vietnam, and several island territories. The accepted synonyms of T. indica according to The Plant List and Medicinal Plant Names Services are Tylophora indica var. indica, Tylophora indica var. glabra (Decne.) H. Huber, and Tylophora indica var. intermedia M.A. Rahman & Wilcock.
The plant is commonly known as Tylophora asthmatica, Emetic Swallow-wort, and Indian or Country-Ipecacuanha. In India, it is named ananthamul and arkaparni in Ayurveda, whereas it is called damnivel by Gujaratis, nanchchurupan by Tamils, and Mendi by the native people of Orissa. Additional English common names include Indian Ipecac, Indian Ipecacuanha, and Emetic Swallowwort. Other names encountered in the literature include Ananthamul, Antomul, Asclepias asthmatica, Country Ipecacuanha, and Cynanchum indicum.
According to the Indian Biodiversity Portal, T. indica (Burm. f.) Merr. is taxonomically placed in the kingdom Plantae, phylum Tracheophyta, class Magnoliopsida, order Gentianales, and family Apocynaceae.
Morphology and Geographic Distribution
Tylophora indica is the most common species in this genus. It is an annual and perennial, small, slender, climbing, and much-branched young herb. Tylophora indica is a perennial, twining herb with a long hairy stem that climbs with the help of tendrils. Leaves are oblong, ovate to elliptical, arranged in an opposite decussate fashion with 12 mm long petioles. Native to India's monsoon forests, this plant stands out with its milky latex, twisted leaves, and delicate lilac flowers.
The plant grows profoundly in Asia, Africa, Australia, Oceanic Islands, Ceylon, the Malay Islands, and Borneo. It is a perennial climbing plant native to the plains, forests, and hills of southern and eastern India. The plant also inhabits elevations up to 1,260 m in the sub-Himalayan tract.
Plant Parts Used and Common Preparations
The portions of the plant used medicinally are the leaves and roots. Traditionally, T. indica has been used in the form of various preparations, including powder, decoction, pulp, paste, and extract, either alone or in combination with other herbs. The plant is a twining herb that is extensively used in folk medicine as a substitute for ipecac, an expectorant.
2. Traditional and Historical Use
Textual Origins in Ayurveda
T. indica was first chronicled in two classical texts of Ayurveda, the Charaka Samhita and the Sushruta Samhita, written around 1000 B.C. These Ayurvedic texts highlight its therapeutic application in asthma. Tylophora has been used traditionally for thousands of years in the Indian tradition of Ayurvedic medicine for lung and breathing problems.
Pharmacopoeial Recognition
The leaves and roots of Tylophora have been included in the Bengal Pharmacopoeia since 1884. Tylophora indica has been included as an official drug in the Bengal Pharmacopoeia of 1884.
Geographic Reach of Traditional Use
T. indica has been traditionally used in India, Bangladesh, and Sri Lanka in the form of various preparations including powder, decoction, pulp, paste, and extract—alone or in combination with other herbs—against ailments like skin disorders, inflammation, cough, asthma, diarrhea, cancer, and microbial infections. Tylophora is common in the Indian subcontinent and other parts of Asia, such as Sri Lanka, Malaysia, Thailand, Australia, and Africa. Since ancient times, the plants of this genus have been used as medicines to treat diseases such as arthritis, gout, jaundice, constipation, flatulence, hemorrhoids, whooping cough, asthma, congestion, and inflammatory skin.
Therapeutic Roles in Traditional Systems
It is said to have laxative, expectorant, diaphoretic (sweating), and purgative (vomiting) properties in traditional usage. Plants from this genus are used in traditional medicine for treating bronchial asthma, rheumatism, allergies, and dermatitis. In addition, the plant has anti-tumor, anti-oxidant, immunomodulatory, and hypotensive activities. It is also used for treating numerous respiratory difficulties, such as asthma, bronchitis, hay fever, the common cold, and coughs. The leaves and roots have been used to treat jaundice and symptomatic liver disorders.
Ethnobotanical surveys have attributed this plant to be antiasthmatic, antiepileptic, antivenom, contraceptive, diuretic, and antidysenteric. In folk preparations for gouty arthritis, the wet roots or leaves were made into a fine paste and applied over the affected joints. A preparation of root powder (250 mg) was administered along with 50–60 ml of a decoction of Guduchi (Tinospora cardifolia) twice daily in gouty arthritis, and this was found effective in gouty arthritis and chronic skin diseases.
Siddha and Other Regional Traditions
Plants of the genus Tylophora have commonly been used in traditional medicine in various communities, especially in the tropical and subtropical regions. Of the nearly 300 species reported in the genus, eight are primarily used in various forms to treat a variety of bodily disorders. Traditional Siddha medicine in South India also records the use of Tylophora for respiratory and inflammatory conditions, with the Sanskrit name Lataksiri appearing in classical manuscripts.
3. Key Constituents and Phytochemistry
Alkaloid Profile — The Phenanthroindolizidine Class
A diverse range of phytochemical constituents have been isolated and identified from T. indica, primarily alkaloids (tylophorine, tylophorinine, tylophorinidine), flavonoids, and terpenoids. Among compounds from various phytochemical classes, phenanthroindolizidine alkaloids—namely tylophorine and tylophorinidine—have been considered the bioactive components of the plant and are widely investigated.
More recently, rare alkaloids including tyloindicines A, B, C, D, E, F, G, H, I, and J, as well as desmethyltylophorine and methyltylophorinindine, have been reported from this plant. Major alkaloid tylophorine has immunosuppressive, anti-inflammatory, anti-tumor, anti-candidal, and anti-amoebic and anticancerous properties, while the alkaloid tylophorinidine has antileukemic properties. Tyloindicines F, G, H, and I, a group of minor alkaloids, are cytotoxic.
Non-Alkaloid Constituents
Other phytochemicals include flavonoids, saponins, tannins, terpenoids, phytosterols, and a fair concentration of primary metabolites. The non-alkaloidal compounds isolated from T. indica include kaempferol, quercetin, α- and β-amyrins, tetratriacontanol, octaosanyl octacosanoate, sigmasterol, β-sitosterol, tyloindane, cetyl alcohol, wax, resin, tannins, glucose, calcium salts, and potassium chloride.
Distribution within the Plant
Phenanthroindolizidine alkaloids isolated from the roots and leaves are largely explored and are considered to be the most active constituents of the plant. The most critical phytochemicals of Tylophora that are accountable for their medicinal application are phenanthroindolizidine alkaloids, which are present primarily in the aerial parts of plants.
4. Mechanisms of Action
Anti-Inflammatory and Immunomodulatory Activity
Laboratory research has shown that the isolated plant extract tylophorine exerts a strong anti-inflammatory action. Test tube studies suggest that tylophorine is able to interfere with the action of mast cells, which are key components in the process of inflammation. Tylophorine, the major alkaloid obtained from T. indica, has been reported to have anti-inflammatory, antiasthmatic, and antianaphylactic potential in experimental studies.
This class of alkaloids has been reported to downregulate cyclin-A2 protein, the mechanism by which these alkaloids induce cell cycle arrest at G1 phase. The alkaloids have also been shown to inhibit the proliferation of vascular smooth muscles through cyclin-D1 downregulation. Moreover, c-JUN mediation, downregulation of NF-κB signaling, and inactivation of the Akt pathways are also reported as potential biomechanisms involved in the anticancer activity of tylophorine alkaloids.
Mechanistically, NF-κB is significantly blocked through the stabilization of its inhibitor protein kappa B alpha (IκBα) under normoxic as well as hypoxic conditions. Both water and hydroalcoholic extracts of T. indica effectively attenuated lipopolysaccharide-induced microglial activation, migration, and the production of nitrite via regulation of the expression of NF-κB and AP1 as the possible underlying target molecules.
Antiasthmatic Mechanisms
Characterization by LC-MS analysis revealed the presence of five major bioactive compounds that showed good docking interactions with M3 and H1 receptors. The ex vivo study demonstrated that the active fraction of T. indica could significantly relax tracheal rings via targeting multiple signaling pathways, namely non-competitive antagonism of histamine and muscarinic receptors, β2-adrenergic stimulation, and activation of soluble guanylyl cyclase. In in vivo studies, the active fraction ameliorated airway hyperresponsiveness and decreased broncho-alveolar lavage fluid (BALF) levels of inflammatory cytokines and immunoglobulin E (IgE).
Phenanthroindolizidine alkaloids are well known for their cytotoxic activity, which is partly attributed to the inhibition of protein and nucleic acid synthesis. Some of these alkaloids were found to possess anti-cancer activity by inhibiting the overexpression of COX-2 enzyme and NF-κB receptors, the deregulation of which is found to cause tumors.
Antiangiogenic and Anticancer Mechanisms
Tylophorine significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, migration, and tube formation of endothelial cells. It directly inhibited VEGFR2 tyrosine kinase activity and its downstream signaling pathways including Akt, Erk, and ROS in endothelial cells. Tylophorine inhibited VEGF-stimulated inflammatory responses including IL-6, IL-8, TNF-α, IFN-γ, MMP-2, and NO secretion. It significantly inhibited neovascularization in a sponge implant angiogenesis assay and also inhibited tumor angiogenesis and tumor growth in vivo. Molecular docking simulation indicated that tylophorine could form hydrogen bonds and aromatic interactions within the ATP-binding region of the VEGFR2 kinase unit.
PBT-1, a tylophorine-based compound, can induce cell cycle G2/M arrest and apoptosis by interrupting the regulatory proteins in cell cycle progression and by inhibiting the NF-κB signaling pathway via inactivation of Akt. This class of tylophorine compounds has a unique mode of action that differs from that of other known antitumor compounds.
5. Scientific Evidence by Area of Use
5.1 Bronchial Asthma and Allergic Rhinitis
Human / Clinical Evidence
A systematic review (Ernst et al., 2000, Thorax) identified 17 randomized clinical trials involving herbal preparations for asthma; eight described traditional Indian medicine, of which five investigated Tylophora indica. No definitive evidence for any of the herbal preparations emerged; while 17 RCTs were found, five of those in the Indian medicine category specifically investigated Tylophora indica.
One clinical trial with asthma sufferers found that tylophora leaf (150 mg of the leaf by weight) chewed and swallowed daily in the early morning for six days led to moderate to complete relief of their asthma symptoms. In a follow-up trial with asthma patients, an alcoholic extract of crude tylophora leaves in 1 gram of glucose had comparable effects to chewing the crude leaf. Another trial found similar success in reducing asthma symptoms using a tylophora leaf powder (350 mg per day). However, tylophora was not as effective as a standard asthma drug combination.
A 12-week follow-up was conducted in one of the double-blind trials. At the end of one week, 62 percent of the Tylophora group had complete to moderate relief in symptoms, as compared with 28 percent of the placebo group.
One double-blind trial failed to show any effect on asthma for tylophora. The studies from the 1970s suggesting benefits of tylophora for asthma were often criticized for their poor design, and subsequent well-designed trials reported mixed results, indicating a need for further research.
Preclinical Evidence
Extracts of the leaves of T. indica have demonstrated antiasthmatic and antiallergic potential in experimental systems. Plant extracts also inhibited the Schultz-Dale reaction and systemic anaphylaxis in guinea pigs. The extract of T. indica leaves showed inhibition of cellular immune responses in experimental models.
Evidence Strength: Mixed and limited. The positive clinical signals from older double-blind trials are counterbalanced by at least one null result and methodological criticisms of the study designs. No large-scale, rigorously controlled modern RCT has been published. Evidence remains insufficient to draw definitive efficacy conclusions.
5.2 Anti-Inflammatory Activity
Preclinical / Mechanistic Evidence
Tylophora indica has been used traditionally as a remedy for various anti-inflammatory conditions including asthma, bronchitis, hay fever, and rheumatism. The major alkaloid tylophorine is considered responsible for the therapeutic efficacies. Anti-inflammatory activity of phenanthroindolizidine alkaloids was examined in an in vitro system mimicking acute inflammation by studying the suppression of lipopolysaccharide (LPS)/interferon (IFN)-induced nitric oxide production in RAW264.7 cells.
Research on tylophorine derivatives indicates that certain compounds may enhance Foxp3 expression through inhibition of the AKT/mTOR pathway and enhancement of demethylation of the promoter region via inhibition of the ERK pathway and DNMT1 expression; one compound acts on the stability of TNF-α mRNA by decreasing phospho-p38 and reduces differentiation of Th17 cells by attenuating interleukin-6 production.
Human Evidence: No clinical trials specifically evaluating tylophora as an anti-inflammatory agent in inflammatory diseases (outside of asthma) have been identified in the peer-reviewed literature.
Evidence Strength: Preclinical only. The anti-inflammatory mechanisms identified in vitro and in animal models are biologically plausible, but translation to human therapeutic outcomes has not been established.
5.3 Cancer — Anticancer and Antiangiogenic Activity
In Vitro Evidence
Tylophorine was found to be cytotoxic against L1210 and P-388 leukemia cells. Tylophorine hindered S-phase progression and arrested cells at G1 phase in human nasopharyngeal carcinoma (HONE-1), hepatocellular carcinoma (HepG2), and gastric cancer (NUGC-3) cell lines.
The in vitro anti-proliferative activity of isolated phenanthroindolizidine alkaloids was evaluated on three different cell lines: MCF-7 (breast), HepG2 (liver), and HCT-116 (colon). Among all isolated compounds, tylophorinidine (compound 5) was the most active cytotoxic agent with the lowest IC50 values at 6.45, 4.77, and 20.08 μM against MCF-7, HepG2, and HCT-116 cell lines, respectively. Compound 5 also exhibited the highest kinase inhibitory activity with the lowest IC50 values (0.6 and 1.3 μM against Aurora-A and Aurora-B enzymes, respectively).
Research on closely related Tylophora species (such as Tylophora ovata) has demonstrated a strikingly potent NF-κB blockade. The compound O-methyltylophorinidine displayed the most potent capacity to inhibit NF-κB-mediated transcription at IC50 values of 17.1 ± 2.0 nM and 3.3 ± 0.2 nM for the plant-isolated and synthetically prepared forms, respectively.
Tylophorine and related natural compounds exhibit potent antitumor activities. Tylophorine compounds comprise a new class of anticancer agents because of their novel chemical structure combined with the unique spectrum of activity compared with current antitumor drugs, based on NCI tumor cell panel studies.
Human Evidence: No human clinical trials evaluating Tylophora extracts or tylophorine for cancer treatment have been identified in the peer-reviewed literature. All anticancer evidence is in vitro or from animal models.
Evidence Strength: Preclinical only. While mechanistic in vitro and in vivo findings are compelling enough to drive ongoing drug development interest—particularly around VEGFR2 inhibition—no clinical data in humans exist.
5.4 Neuroinflammation
T. indica is a valuable medicinal plant well known in Ayurvedic practices for its immunomodulatory, anti-oxidant, anti-asthmatic, and antirheumatic activities. Both water and hydroalcoholic extracts of T. indica effectively attenuated lipopolysaccharide-induced microglial activation, migration, and the production of nitrite via regulation of the expression of NF-κB and AP1 as the possible underlying target molecules. T. indica may prove to be a potential anti-neuroinflammatory agent and may be further explored as a potential therapeutic candidate for the management of neurodegenerative diseases.
Evidence Strength: Preliminary and preclinical in vitro only. No human data exist in this area.
5.5 Diarrhea and Dysentery
Among the traditional uses of T. indica, the antiasthmatic and antidysenteric properties have been supported by different investigations including animal models and some clinical work, but conventional uses such as its role as a contraceptive and antivenom need further scrutiny. This plant has been in use for the therapy of numerous ailments including cough, bronchitis, diarrhea, dysentery, cancer, arthritis, microbial infections, and epilepsy by Asian populations.
Evidence Strength: Traditional use is well-documented. Preclinical/animal model evidence exists for antidiarrheal activity, but rigorous human clinical evidence is absent.
5.6 Antimicrobial Activity
Different parts of the plant are associated with anti-asthmatic, antibacterial, anti-psoriasis, antimicrobial, antiulcer, antiallergic, antidiarrheal, hypolipidemic, and anxiolytic properties. Pharmacologically, a few plant species from the genus have exhibited broad-spectrum anti-microbial and anti-cancer activity, which has been proven through experimental evaluations.
Evidence Strength: In vitro and preclinical only. No human clinical trials for antimicrobial indications have been published.
5.7 Rheumatism and Joint Conditions
Tylophora indica has long-standing use as a folk remedy for asthma and other respiratory problems, and is also used in conditions like rheumatism and dermatitis. Research has focused on the phytoconstituents of the plant and their potential for targeting rheumatoid arthritis. Animal model and in vitro evidence for anti-arthritic activity exists, but no dedicated human clinical trials for rheumatoid or gouty arthritis specifically using tylophora have been robustly published in the indexed literature.
Evidence Strength: Traditional use well-documented; limited supportive preclinical data; human clinical evidence absent.
6. Body Systems and Health Areas of Association
- Respiratory system: Tylophora is used for treating numerous respiratory difficulties such as asthma, bronchitis, hay fever, the common cold, and coughs.
- Immune system: Certain plants from the genus have found use as anti-inflammatory, anti-tumor, anti-allergic, smooth muscle relaxant, immunomodulatory, and free-radical scavenger agents.
- Gastrointestinal system: Preparations have been used against conditions including diarrhea and dysentery.
- Skin: Skin disorders have been among the traditional indications, and topical preparations have been described.
- Hepatic/biliary: The leaves and roots have been used to treat jaundice and symptomatic liver disorders.
- Musculoskeletal system: Plants of the genus are used to treat arthritis and gout.
- Central nervous system (neuroinflammation): T. indica may prove to be a potential anti-neuroinflammatory agent and may be further explored as a potential therapeutic candidate for the management of neurodegenerative diseases.
- Oncology (experimental): In vitro and in vivo pharmacological studies have revealed its potential as an anticancer agent.
7. Dosage Forms and Reported Dosages
In traditional Ayurvedic practice, the alkaloid of Tylophora in powder form, about 400–500 milligrams, has been given once daily to asthmatic patients for six days to treat asthma.
Traditionally, doses of 250 milligrams one to three times daily, standardized to 0.1% of tylophorine per dose, have been used.
Some clinical trial reports describe using 350 milligrams of Tylophora leaf placed in a capsule, given once daily for seven days.
In one of the pioneering double-blind human trials, each patient was given one leaf daily for six days only.
A dosing reference from clinical practice cited in the peer-reviewed literature describes Tylophora leaf—200 to 400 mg of the dried leaf per day, or 1 to 2 ml of tincture per day—as a range used to treat asthma.
Across studies, gastrointestinal side effects are more common among participants who chew whole leaves rather than dried leaves or powdered extract in capsule form.
8. Safety Considerations and Toxicology
Observed Adverse Effects in Human Studies
Tylophora has caused nausea, vomiting, mouth soreness, and alterations in taste sensation in a significant number of participants in several studies. Tylophora has been reported to cause infrequent nausea, vomiting, change in taste perception, and mouth soreness. Rare instances of drowsiness and respiratory distress have also been reported.
Relationship Between Formulation and Side Effects
Symptoms are more common among participants who chew whole leaves rather than dried leaves or powdered extract in capsule form; however, the therapeutic benefits of the herb are also reduced as side effects decrease.
Preclinical Toxicology
Preliminary studies on animals have found Tylophora extracts to be toxic only in extremely high doses; these extracts were apparently safe in the far smaller doses needed to produce a therapeutic effect. Toxicology studies have shown that T. indica is generally safe; however, it may cause significant toxicities at higher doses. Bembde et al. (2018) reported that a hydroalcoholic extract of T. indica is safe up to doses of 2,000 mg/kg when administered orally, without any observed toxicity in Wistar rats.
Potential Interaction with the Pituitary–Adrenal Axis
Although not well studied in humans, Tylophora may antagonize dexamethasone/hypophysectomy-induced suppression of the pituitary. Caution is advised when taking Tylophora with herbs or supplements with corticosteroid-like effects.
Abortifacient and Reproductive Concerns
Tylophora is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence. Tylophora asthmatica has been reported to have abortion-inducing properties. Many tinctures also contain high levels of alcohol, which should be avoided during pregnancy.
Populations Requiring Caution
Use cautiously in patients with diabetes, congestive heart failure, arrhythmia, hypertension, and edema. Tylophora should be avoided in patients with serious infections, organ transplantation, major systemic disease, or those who have undergone major recent surgery.
Overall Evidence Gaps
Despite its long-standing use in traditional medicine, modern scientific evidence remains inconclusive regarding its anti-inflammatory and antiallergic effects. Additionally, Tylophora can cause side effects such as nausea and mouth soreness, particularly when consumed in certain forms. T. indica is considered an endangered species, and its genetic preservation is a matter of ongoing concern.
References
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