Medicinal Plants in Dermatology: Podophyllotoxin
Learn about the history, composition, and modern applications of a scientifically proven plant-derived therapy for skin conditions.
This post is part of a series where I break down the topics covered in our recently published review article on plants used in dermatology. Today, we’re covering podophyllotoxin from mayapple plants.
Israyilova, A., T.V. Peykova, B. Kittleson, P.C. Sprowl, T.O. Mohammed, C.L. Quave. (2025) From Plant to Patient: A Historical Perspective and Review of Selected Medicinal Plants in Dermatology. JID Innovations, 5:1: 100321
Discovery and Composition
Podophyllotoxin, a natural compound found in plants of the Podophyllum genus, commonly known as mayapple, is most abundant in Podophyllum emodi. Historically, extracts rich in podophyllotoxin were used in traditional medicine for treating parasitic infections and poisonings. In the 1940s, it was successfully used to treat venereal warts.
History as a Drug
Introduced into the U.S. Pharmacopoeia in 1820, it was initially used to treat venereal warts. Today, podophyllotoxin creams (0.15–0.5%) and gels, such as FDA-approved Podofilox, are used to treat anogenital warts, offering the convenience of self-application. Podophyllotoxin has also shown promise in managing molluscum contagiosum, viral infections like herpes and measles, and keratoacanthoma. In New Zealand, it is available by prescription as a 0.15% w/w cream (Wartec) and 5 mg/ml solution (Condyline) for external genital warts. Beyond skin applications, podophyllotoxin derivatives has been explored for diverse conditions, including tropical diseases like malaria, autoimmune disorders, mental illnesses, and neurological diseases. While effective for some conditions, challenges like limited penetration in thick skin coatings can reduce its efficacy for cutaneous warts.
Mode of Action
Podophyllotoxin works by disrupting cell division and metabolism. It inhibits topoisomerase II, causing DNA breaks, and prevents mitosis by binding to tubulin, a key protein in cell division. This action leads to the necrosis of wart tissue and interferes with cellular metabolism and energy production. The active compounds in podophyllin resin include podophyllotoxin and related molecules, some of which show potent anticancer and antiviral properties.
Podophyllotoxin's unique structure, including its chiral centers and functional groups, contributes to its effectiveness. Modifying specific parts of its structure can influence its activity, drug resistance, and water solubility. It has demonstrated strong anticancer effects, particularly by blocking microtubule assembly and inducing programmed cell death in cancer cells. Studies have shown its ability to reduce tumor cell viability in bladder cancer and leukemia, highlighting its potential for therapeutic advancements in cancer treatment.
Uses in Dermatology Today
Genital Warts
Podophyllotoxin is used to treat genital warts, including those caused by HPV, a sexually transmitted virus. HPV can infect the genital and anal areas, with over 70 subtypes identified, some linked to cancer risk. Podophyllotoxin has proven effective in clinical trials, clearing 74% of genital warts compared to 18% with placebo, and is included in FDA-approved treatments like Wartec and Condylox.
Podophyllotoxin is applied topically, often with benzoin tincture, and is more effective and affordable than similar clinical treatments. Side effects include redness, stinging, and swelling but are less severe than with other therapies. Classified as category-C for pregnancy, it is contraindicated during this time. Beyond warts, podophyllotoxin shows promise in treating psoriasis, rheumatoid arthritis, and certain viral infections, thanks to its anti-inflammatory and immune-modulating properties.
Podophyllotoxin Analogs in Cancer and Emerging Treatments
Podophyllotoxin structural derivatives, including etoposide and teniposide (see figure above for chemical structures), are key anticancer agents used to treat lung cancer, Wilms’ tumor, genital tumors, and lymphomas. Combination therapies, like mixing podophyllotoxins with cisplatin, have shown promise against neuroblastomas and genital infections. Etoposide, a semi-synthetic derivative, was explored in clinical trials for treating severe COVID-19 cytokine storms, though results were inconclusive.
Efforts to improve these treatments include modifying podophyllotoxin’s structure, especially at its C-4 position, to counter drug resistance. Synthetic production is gaining attention due to the limited natural availability of mayapple plants, which are threatened by habitat loss and climate change. Biosynthesis and plant cell cultures are being explored as sustainable solutions to meet the growing demand for these effective medications. Podophyllotoxin's versatility highlights its importance in both cancer therapy and emerging medical applications.
I hope you enjoyed learning a bit about this important plant-derived medicine!
Yours in health, Dr. Quave
Cassandra L. Quave, Ph.D. is a Guggenheim Fellow, CNN Champion for Change, Fellow of the National Academy of Inventors, recipient of The National Academies Award for Excellence in Science Communication, and award-winning author of The Plant Hunter. Her day job is as professor and herbarium curator at Emory University School of Medicine, where she leads a group of research scientists studying medicinal plants to find new life-saving drugs from nature. She hosts the Foodie Pharmacology podcast and writes the Nature’s Pharmacy newsletter to share the science behind natural medicines. To support her effort, consider a paid or founding subscription to Nature’s Pharmacy or donation to her lab research.
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