IngredientsTylophorine is the principal bioactive alkaloid of Tylophora indica (Burm. f.) Merr., a perennial climbing plant. T. indica is taxonomically included in the kingdom Plantae, phylum Tracheophyta, class Magnoliopsida, order Gentianales, and family Apocynaceae. The plant is also classified under the older family designation Asclepiadaceae in much of the pharmacological literature. The accepted botanical synonyms of T. indica (Burm. f.) Merr. according to The Plant List and Medicinal Plant Names Services include Tylophora indica var. indica, Tylophora indica var. glabra (Decne.) H. Huber, and Tylophora indica var. intermedia M.A. Rahman & Wilcock.
In the latter half of the 19th century, it was called Indian ipecacuanha, as the roots of the plant have often been employed as an effective substitute for ipecac. Common names recorded across its native range include ananthamool, antamul, and lataksiri in Sanskrit and regional Indian languages.
The plant can be found at an elevation of 1,260 m in the sub-Himalayan tract and central peninsular India, and is observed growing in plains and hilly land in various Indian states including Assam, Bengal, and Orissa. Tylophora asthmatica (a common synonym) is a medicinal perennial vine found in eastern, central, and southern India, Sri Lanka, Thailand, Malaysia, and Borneo.
Tylophorine (C₂₄H₂₇NO₄) is a bioactive secondary metabolite present in T. indica. It contains organonitrogen heterocyclic and organic heteropentacyclic compounds. Its IUPAC name is (13aS)-2,3,6,7-tetramethoxy-9,11,12,13,13a,14-hexahydrophenanthro[9,10-f]indolizine. It has a tertiary base with a 2,3,6,7-methoxyl-substituted phenanthrene ring system joined with an indolizidine ring at its 9,10-position. The molecular formula is C₂₄H₂₇NO₄ and the molecular weight is 393.194 g/mol.
Tylophorine and its analogs are phenanthroindolizidine alkaloids, several of which have been isolated from the Tylophora genus of plants. The family Asclepiadaceae produces phenanthroindolizidine alkaloids as major secondary metabolites, and these compounds are considered extremely important phytochemicals due to their intense cytotoxic effects.
While T. indica is the most studied source, tylophorine and closely related phenanthroindolizidine alkaloids have been identified across the genus Tylophora, which comprises over fifty plant species. The tylophorine alkaloids, originating from the plant Tylophora indica, of the genus Tylophora (which comprises over fifty plant species), have primarily been reported for their anti-asthmatic, immunostimulant, respirative soothing, and digestive properties. Tylophorine has also been isolated from Tylophora ovata, Tylophora atrofolliculata, and other species within the family.
A diverse range of phytochemical constituents have been isolated and identified from T. indica, namely the alkaloids tylophorine, tylophorinine, and tylophorinidine. UPLC-MS studies have yielded preliminary identification of 32 metabolites, with tylophorine, tylophorine B, tylophorinine, and tylophorinidine being the predominant metabolites. The plant also elaborates a wider series of phenanthroindolizidine alkaloids including tylocrebrine, septicine, antofine, isotylocrebrine, and dehydrotylophorine, as well as several N-oxide derivatives.
The structural relationships among the principal alkaloids have been elucidated. The IUPAC name of tylophorinidine (C₂₂H₂₂NO₄) is (13aS,14S)-3,7-dimethoxy-9,11,12,13,13a,14-hexahydrophenanthro[10,9-f]indolizine-6,14-diol, with a molecular weight of 365.4 g/mol.
The presence of a crystalline alkaloid, tylophorine, in roots was first reported by Hooper (1891) using characteristic color reactions. Tylophorine and tylophorinine were isolated from T. indica, and their chemical structures were confirmed using X-ray studies by Govindachari and colleagues (1957, 1960, 1965).
T. indica has been used in the form of various preparations including powder, decoction, pulp, paste, and extract, alone or in combination with other herbs. In modern dietary supplement contexts, the plant is encountered as dried leaf powder in capsule form, alcoholic (ethanolic) tinctures, and standardized extracts. Doses of 250 mg one to three times daily, standardized to 0.1% tylophorine per dose, have been reported in various studies. Tylophora leaf at 200 to 400 mg of the dried leaf per day, or 1 to 2 ml of tincture per day, has been cited for use in asthma.
According to historical records, T. indica was first chronicled in two classical texts of Ayurveda — the Charaka Samhita and Sushruta Samhita — written around 1000 B.C. These ancient texts therefore represent among the earliest documented medicinal applications of the plant from which tylophorine is derived.
T. indica has been traditionally used in India, Bangladesh, and Sri Lanka in the form of various preparations like powder, decoction, pulp, paste, and extract — alone or in combination with other herbs — against various ailments including skin disorders, inflammation, cough, asthma, diarrhea, cancer, and microbial infections.
The leaves of the plant have been extensively used in the treatment of various inflammatory and allergic disorders like bronchial asthma, bronchitis, and whooping cough. Tylophora indica (family Apocynaceae) is a perennial climbing plant that has been used in the Ayurvedic system of medicine.
The plant has been traditionally used as a folk remedy in certain regions of India for the treatment of bronchial asthma, bronchitis, rheumatism, and dermatitis. Tylophora indica is an extensively used Indian traditional medicine to cure various human ailments, acting as a folk remedy for the treatment of bronchial asthma, inflammation, bronchitis, allergies, rheumatism, and dermatitis.
The use to induce vomiting led to tylophora's inclusion in the Bengal Pharmacopoeia of 1884. This pharmacopoeial listing marks one of the earliest formal recognition of the plant in an official compendium, reflecting both its emetic properties (attributed to the alkaloid content) and its established use in regional medicine.
Ethnobotanical surveys have attributed this plant to be antiasthmatic, antiepileptic, antivenom, contraceptive, diuretic, antidysenteric, and other uses. Some of these claimed potentials (antiasthmatic and antidysenteric) have been supported by different investigations including animal models and clinical trials, but conventional uses such as contraceptive and anti-venom remain in need of further scrutiny.
The major constituent in tylophora is the alkaloid tylophorine. Laboratory research has shown this isolated plant extract 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.
The major alkaloid tylophorine found in T. indica possesses several properties, including immunosuppressive, antitumour, antifeedant, antibacterial, antifungal, antiamoebic, diuretic, and hepatoprotective activities. In addition, tylophorine provides positive stimulation to the adrenal cortex.
One of the most rigorously characterized mechanisms of tylophorine and its analogs is inhibition of eukaryotic protein synthesis. The ability of chemically related compounds including emetine and cryptopleurine to inhibit translocation has been known since the 1970s. Chemically related cephaeline, tylophorine, tylocrebrine, tubulosin, DCB-3503, and YXM-110 also inhibit translocation and presumably bind to the same region of the 40S ribosomal subunit.
Studies using the tylophorine analog DCB-3503 have elucidated this mechanism in detail. DCB-3503 suppresses the expression of pro-oncogenic or pro-survival proteins with short half-lives, including cyclin D1, survivin, β-catenin, p53, and p21, without decreasing their mRNA levels. A proteasome inhibitor reversed the inhibitory effect on expression of these proteins. DCB-3503 inhibited the incorporation of radiolabeled amino acid and thymidine. The mechanism of inhibition of protein synthesis is different from that of cycloheximide, and, in contrast to rapamycin, DCB-3503 does not affect protein synthesis through the mTOR pathway. DCB-3503 treatment shifts the sedimentation profiles of ribosomes and mRNAs towards the polysomal fractions while diminishing monosome abundance, indicative of inhibition of the elongation step of protein synthesis.
Tylophorine possesses antiproliferative action in cancer cells; it rapidly diminishes cyclin D1, reduces protein biosynthesis, and prevents vascular smooth muscle cell proliferation in vitro.
Studies using purified tylophorine on vascular smooth muscle cells confirmed the mechanism: tylophorine inhibited PDGF-BB-induced proliferation of rat aortic vascular smooth muscle cells by arresting cells in G1 phase of the cell cycle with an IC₅₀ of 0.13 µmol/L; the lack of retinoblastoma protein phosphorylation and cyclin D1 downregulation corroborated a G1 arrest.
The molecular mechanism underlying cyclin D1 suppression by the analog DCB-3503 has been characterized further: DCB-3503 preferentially binds to heat shock cognate protein 70 (HSC70), which is a determinant for cyclin D1 translation by binding to the 3'-untranslated region (3'-UTR) of its mRNA. DCB-3503 allosterically regulates the ATPase and chaperone activities of HSC70 by promoting ATP hydrolysis in the presence of specific RNA binding motifs (AUUUA) of cyclin D1 mRNA.
Other involved biomechanisms, including 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.
DCB-3503 could affect cell cycle regulatory proteins and is a potent modulator of NF-κB function. It is a potentially useful compound in the management of cancers in which cyclin D1 overexpression and high NF-κB activity play a pivotal role. Work using related phenanthroindolizidine alkaloids from T. ovata corroborated this pathway: a remarkably effective blockade of nuclear factor kappa B (NF-κB) within 2 hours was demonstrated for O-methyltylophorinidine (IC₅₀ = 17.1 ± 2.0 nM for natural compound). NF-κB inhibition data for analogues indicate a structure-activity relationship. Mechanistically, NF-κB is significantly blocked through the stabilization of its inhibitor protein kappa B alpha (IκBα) under both normoxic and hypoxic conditions.
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.
Using HUVECs (human umbilical vein endothelial cells), it was demonstrated that tylophorine inhibited VEGF-stimulated inflammatory responses including IL-6, IL-8, TNF-α, IFN-γ, MMP-2, and NO secretion. Tylophorine significantly inhibited neovascularization in a sponge implant angiogenesis assay. Molecular docking simulation indicated that tylophorine could form hydrogen bonds and aromatic interactions within the ATP-binding region of the VEGFR2 kinase unit, leading to the conclusion that tylophorine exerts anti-angiogenesis effects via the VEGFR2 signaling pathway.
Plant extracts 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. Various studies have shown that alkaloids of Tylophora indica suppress cellular immune response.
Phenanthroindolizidine alkaloids as a class prevent the synthesis of DNA and proteins, a mechanism documented in the literature since the late 1990s. This class of alkaloids has been reported for downregulation of cyclin-A2 protein, the mechanism by which these alkaloids induce cell cycle arrest at G1 phase. The alkaloids have also been shown to successfully inhibit the proliferation of vascular smooth muscles through cyclin-D1 downregulation.
Human / Clinical Evidence:
Bronchial asthma represents the area with the most substantial human clinical trial data for tylophorine-containing preparations. Seventeen randomised clinical trials on herbal preparations for asthma have been identified in systematic searches, of which five 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 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. One double-blind trial failed to show any effect on asthma for tylophora.
A crossover, double-blind study (Shivpuri et al., 1969) enrolled 110 patients with bronchial asthma. The 110 asthmatic patients took either tylophora or placebo (spinach) leaves, which were cut into small pieces by non-medical staff, put into polythene bags, and given code names by a statistician. Each patient was given one leaf daily for 6 days only. At the end of one week, 62 per cent of the tylophora group had complete to moderate relief in symptoms, as compared with 28 per cent of the placebo group.
In the Cochrane Systematic Review, tylophora showed impressive short-term improvements in clinical outcomes of attack frequency and symptom severity, and moderate improvements in lung function measurements, but positive effects were not evident after 12 weeks. Investigators noted that this herb may not be suitable for chronic use because it is also associated with severe gastrointestinal side effects — sufficient to lead one of the investigators to include an antiemetic agent in the placebo comparator to mask treatment group assignment.
In an earlier systematic review identifying 5 randomized clinical trials, 3 demonstrated moderate improvement of symptoms (1 with improved FEV1), and 2 studies showed no significant improvement compared with placebo for the 2-week trials.
A systematic review of herbal medicines for asthma concluded that no definitive evidence for any of the herbal preparations emerged. Results identified 17 randomised clinical trials, six of which concerned traditional Chinese herbal medicine and eight described traditional Indian medicine, of which five investigated Tylophora indica.
Evidence strength: Clinical evidence from multiple double-blind, randomized controlled trials suggests short-term symptomatic benefit; however, effects are not sustained beyond 12 weeks, methodological quality is variable, and no definitive conclusions have been drawn in systematic reviews. The evidence is preliminary-to-moderate and does not support conclusions about long-term efficacy or clinical equivalence to established asthma therapeutics.
Preclinical Evidence:
Laboratory research has shown that tylophorine isolated from tylophora 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.
An ex vivo study demonstrated that active fractions of T. indica could significantly relax tracheal rings via targeting multiple signalling pathways, including noncompetitive antagonism of histamine and muscarinic receptors, β2-adrenergic stimulation, and activation of soluble guanylyl cyclase. In in vivo studies, active fractions ameliorated airway hyperresponsiveness and decreased broncho-alveolar lavage fluid levels of inflammatory cytokines and immunoglobulin E. These results confirm the traditional use of T. indica as an antiasthmatic agent.
Evidence strength: Evidence for anti-inflammatory and immunomodulatory activity is based on in vitro and animal studies and is mechanistically robust at the preclinical level. No independent human clinical trials have specifically evaluated these endpoints.
Preclinical Evidence (in vitro and in vivo):
Evaluation of (+)-S-tylophorine [DCB-3500 (NSC-717335)] and its analog DCB-3503 (NSC-716802) in the National Cancer Institute tumor screen showed a fairly uniform and potent inhibition of cell growth in all 60 cell lines (GI₅₀ ∼10⁻⁸ m).
All four tylophorine analogs evaluated exerted potent growth-inhibitory effects against HepG2 (human hepatocellular carcinoma) and KB (human nasopharyngeal carcinoma) cell lines. HepG2 cells were more sensitive than KB in terms of loss of clonogenicity. KB variants resistant to etoposide, hydroxyurea, or camptothecin had similar sensitivities to the tylophorine analogs as parental KB cells.
The cytotoxicity of extracts of T. indica was evaluated on HepG2 and MCF-7 cell lines, yielding IC₅₀ values of 75.71 µg/mL and 69.60 µg/mL, respectively.
Tylophorine significantly inhibited neovascularization in a sponge implant angiogenesis assay and also inhibited tumor angiogenesis and tumor growth in vivo.
To better mimic the triple-negative breast cancer (TNBC) microenvironment in vitro, researchers established a 3D co-culture combining the human TNBC cell line MDA-MB-231 with primary murine cancer-associated fibroblasts and type I collagen. One phenanthroindolizidine compound demonstrated superiority against the therapeutic gold standard paclitaxel by diminishing spheroid growth by 40% at 100 nM.
Among all the isolated compounds from T. indica, tylophorinidine 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. Bioactivities were also validated by in vitro kinase receptor inhibition assay. Compound 5 (tylophorinidine) also exhibited the highest activity with lowest IC₅₀ values of 0.6 and 1.3 µM against Aurora-A and Aurora-B enzymes, respectively.
Evidence strength: Anticancer evidence is entirely preclinical — comprising in vitro cell line studies and animal tumor xenograft models. There are no human clinical trials evaluating tylophorine or its analogs as cancer treatments. The preclinical data, while extensive and mechanistically detailed, does not establish clinical efficacy or safety in humans for oncological indications.
Preclinical Evidence:
Tylophorine inhibited the growth of Entamoeba histolytica (polyaxenic and axenic strains), exhibiting amoebicidal activity at non-toxic doses.
Significant antibacterial activity (P<0.05) was observed against Staphylococcus aureus and Staphylococcus epidermidis in alcoholic leaf callus extract. Against these gram-positive bacteria, no significant activity was exhibited by the aqueous leaf callus extract. No activity was observed against gram-positive bacteria in alcoholic or aqueous extracts of root and nodal calli.
Evidence strength: Evidence for antimicrobial and antiamoebic activity is based exclusively on in vitro studies. No clinical trials in humans have been conducted for these indications.
Preclinical Evidence:
Tylophorine is an alkaloid with antiproliferative action in cancer cells. Vascular smooth muscle cell (VSMC) proliferation and neointima formation contribute to restenosis after percutaneous coronary interventions. Researchers examined the potential of tylophorine to inhibit VSMC proliferation and migration and to dissect underlying signaling pathways. Tylophorine inhibited PDGF-BB-induced proliferation of rat aortic VSMCs by arresting cells in G1 phase of the cell cycle with an IC₅₀ of 0.13 µmol/L. The lack of retinoblastoma protein phosphorylation and cyclin D1 downregulation corroborated a G1 arrest. Inhibition of proliferation and cyclin D1 downregulation were species- and stimulus-independent.
Evidence strength: Preclinical only. No human data exist for cardiovascular applications.
Different formulations and dosing regimens have been reported from various studies, but doses of 250 mg one to three times daily, standardized to 0.1% of tylophorine per dose, have been reported.
In the clinical trials for asthma conducted by Shivpuri and colleagues, each patient was given one leaf daily for 6 days only, while another trial used 150 mg of leaf by weight chewed and swallowed daily in the early morning for six days, and yet another trial used a tylophora leaf powder at 350 mg per day.
Tylophora leaf at 200 to 400 mg of the dried leaf per day, or 1 to 2 ml of tincture per day, has been cited in the herbal medicine literature for use in asthma.
Safety data only exist for 6- to 14-day exposures. Short-duration use reflects both the nature of the clinical trials conducted and the documented side-effect profile.
Patients using tylophora may experience temporary nausea and vomiting, soreness of the mouth, and loss of taste for salt, particularly with the fresh leaf and tincture preparations.
Tylophora is associated with severe gastrointestinal side effects — sufficient to lead one investigator to include an antiemetic agent in the placebo comparator to mask treatment group assignment. The incidence of side effects such as nausea, partial diminution of taste for salt, and slight mouth soreness was 16.3% in the Tylophora group and 6.6% in the placebo group in one trial.
Adverse effects mainly seem to be gastrointestinal, including nausea and vomiting, and these seem to be reduced if the leaves are taken in capsule form instead of raw or tincture form.
Safety data only exist for 6- to 14-day exposures. The long-term safety profile of tylophorine in humans has not been formally evaluated. Investigators noted that this herb may not be suitable for chronic use based on the side-effect observations from clinical trials.
In acute oral toxicity studies, the methanolic extract of T. indica was found toxic on rat liver at a dose of 200 mg/kg and higher doses, with an LD₅₀ of 223.6 mg/kg. These preclinical toxicological data indicate a relatively narrow margin between therapeutic and toxic doses in animal models, though direct extrapolation to human therapeutic ranges must be made cautiously.
The safety of tylophora for use during pregnancy and breast-feeding has not been established.
In the latter half of the 19th century, T. indica was called Indian ipecacuanha, as the roots have often been employed as an effective substitute for ipecac. The use to induce vomiting led to its inclusion in the Bengal Pharmacopoeia of 1884. This historical recognition of its emetic potential is consistent with the nausea and vomiting observed in modern clinical trials.
At the time of documentation in available clinical references, there were no well-known supplement or food interactions identified with this supplement. Given its documented immunosuppressive properties and effects on cellular regulatory proteins, potential interactions with immunosuppressive drugs, chemotherapeutic agents, or biologics targeting NF-κB or VEGF pathways represent theoretical concerns that have not been clinically evaluated.
Health conditions that Tylophorine may help support.
Tylophorine is the primary alkaloid of Tylophora indica responsible for its anti-asthmatic properties. It has immunomodulatory effects including suppression of Th2-mediated inflammation and has been studied in relation to asthma, being the active constituent behind tylophora leaf's documented clinical effects in bronchial asthma trials.
Body systems that Tylophorine may help support.
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