Medical attributes of Podophyllum peltatum

Medical Attributes of Podophyllum peltatum - Mayapple

by Kevin Anderson, Colleen Pike, Katrina Toporcer
Wilkes University
Wilkes-Barre, PA

July, 2013

Podophyllum peltatum is a perennial herb that grows to a height of approximately 1’ and is found in deciduous forests throughout North America (PFAF). A member of the Berberidaceae (Barberry family) (wildflower.org), P. peltatum is commonly known as the American mayapple; as well as umbrella plant, Indian apple, hog apple, and American mandrake (Fondren 1998). It has one or two two large umbrella-like leaves from which its name is derived; The Greek words podos and phyllon, mean “foot shaped leaves” while peltatum means “shield-like” (Fondren 1998). A white flower resembling an apple blossom grows in the axil of the two leaves in May, giving the plant the common name Mayapple (wildflower.org). Mayapple is a rhizomatous herb and is usually found growing in large colonies (Fondren 1998).

Mayapple has been used in a variety of ways amongst different cultures. Although the leaves, roots, seeds and unripe fruit of the Mayapple are poisonous, the ripened fruit is edible (wildflower.org). Many Native Americans used Mayapple as an antihelmintic, diuretic and cathartic (Ray 2009). The Penobscot and Cherokee Indians used Mayapple as an external treatment for warts, emetic, hepatic stimulant, and as a laxative (Fondren 1998). Mayapple was also used as a traditional Chinese Herbal to treat snake bites, fatigue, genital warts, and tumors (Chang et al. 1992).

Podophyllum peltatum contains lignans, which are a widely distributed class of dimeric phenylpropanoid derivatives, many of which have medical significance. Leading among these lignans, podophyllotoxin is a cytotoxic inhibitor of an animal’s cell cycle and the primary toxin produced by P. peltatum (Moraes et. al. 2007). Podophyllotoxin and its derivatives exhibit pronounced biological activity mainly as strong antiviral agents, and as antineoplastic drugs (Canel et. al. 2000). Podophyllotoxin is extracted from the plant’s stem and rhizome (Giri & Narusu 2000). The podophyllotoxin derivative etoposide has been successfully utilized in the treatment of a variety of malignant conditions (Canel et. al. 2000). Podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking microtubular assembly. However, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), via inhibition of DNA synthesis (Sinkule 1984). Therefore, etoposide can be utilized as natural medicine due to its inhibition of DNA topoisomerase which is the clinical target for anticancer drugs. DNA topoisomerases are the cellular enzymes that change the topological state of DNA through the breaking and rejoining of DNA strands (Baikar & Malpathak 2010).

Podophyllotoxin derivatives, etoposide, etopohos and teniposide, are the starting material for the semi-synthesis of anti-cancer drugs. These compounds have been used for the treatment of small and large cell lung, refractory testicular, stomach, pancreatic cancers, and myeloid leukemias. These compounds are also precursors to other derivatives that are being tested for rheumatoid arthritis, psoriasis and malaria (Moraes et. al. 2002). P. peltatum combination therapies are currently being implemented with other chemotherapeutic agents that are useful in the fight against viral infections and cancer (Geuerram et.al 2003). Podophyllotoxin shows promise in being a potent candidate for the design and synthesis of more potent, less toxic and more selective compounds in anti-cancer treatment.

Podophyllotoxin is a commonly used remedy for the treatment of genital warts. In a clinical trial of 56 patients, podophyllotoxin treatment was seen as very effective in the removal of warts compared to a placebo group. 73% of the original warts in podophyllotoxin treated patients were resolved compared to only 8% of those in the placebo group (Beutner et. al. 2003). It is effective in wart clearance in about one half of cases, but is associated with a high recurrence rate. Its advantages are that it is safer, inexpensive and can be easily self-administered (Chang & Welton 2004).

As effective as P. peltatum’s constituents may seem to be, podophyllotoxin and its derivatives were shown to have adverse reactions even when used correctly. According to a study of podophyllotoxin for the treatment of genital warts, when the medication was administered correctly, no systemic adverse reactions were evident, although there were some cases where transient inflammation, erosion, pain, and burning were recorded (Beutner et. al. 2003). However if podophyllotoxin is used incorrectly or is accidentally ingested, symptoms may include nausea, vomiting, diarrhea, abdominal pain, thrombocytopenia, abnormal liver function tests, sensory ataxia, altered consciousness and persistent peripheral tingling or numbness (Kao 1992). In a clinical trial of the derivative etoposide, symptoms included decreased white blood cell count and peripheral neuropathies (Mantle, Lennard, & Pickering 2000).

Podophyllum peltatum contains the richest source of podophyllotoxin in the Berberidaceae. Mayapple has been heavily bioprospected and laboratories are currently developing a synthetic remedy to enhance the availability of Mayapple treatment (Moraes et. al. 2002). Mayapple has endured through the centuries as a valuable medicinal herb, and continues to persist and prove its ongoing worth to the medical world today.

LITERATURE CITED

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Beutner, K.R., M.A. Conant, A.E. Friedman-Kien, et al. 2003. Patient-applied podofilox for treatment of genital warts. The Lancet 33:831-834.

Canel, C., R. Moraes, F. Dayan, & D. Ferreira. 2000. Podophyllotoxin. Phytochemistry 54:115-120.

Chang, G.J. & M.L. Welton. 2004. Human papillomavirus, Condylomata acuminata, and anal neoplasia. Clinical Colon Rectal Surgery 17: 221–230.

Chang, L.W., C.M. Yang, C.F. Chen, & J.F. Deng. 1992. Experimental Podophyllotoxin (bajiaolian) poisoning: I. Effects on the nervous system. Biomed Environmental Science 5:283-92.

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Fondren, B.T. 1998. Mayapple. Ethnoleaflets.com. Southern Illinois University Carbondale. http://www.ethnoleaflets.com/leaflets/mayapple.htm. Accessed 22 June 2013.

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Kao, F. 1992. Podophyllotoxin intoxication: Toxic effect of bajiaolian in herbal therapeutics. Human Experimental Toxicology 11:480-487.

Mantle, D., T. Lennard, & A. Pickering. 2000. Therapeutic applications of medicinal plants in the treatment of breast cancer: a review of their pharmacology, efficacy and tolerability. Adverse Drug Reactions and Toxicological Reviews 19:223-240.

Moraes, R., et al. 2000. The American mayapple revisited—Podophyllum peltatum—still a potential cash crop? Economic Botany 54:471-476.

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Moraes, R., F. Dayan., & C. Canel. 2007. The lignans of Podophyllum. Studies in Natural Products Chemistry 26:149-182. Podophyllum peltatum L. Pfaf.org. Plants for a Future. Accessed 22 June 2013. http://www.pfaf.org/user/Plant.aspx?LatinName=Podophyllum+peltatum.

Podophyllum peltatum L. 2012. Wildflower.org. Lady Bird Johnson Wildflower Center. http://www.wildflower.org/plants/result.php?id_plant=POPE. Accessed 22 June 2013.

Ray, L.E. 2009. Podophyllum peltatum and observations on the Creek and Cherokee Indians: William Bartram’s preservation of native American pharmacology. Yale Journal of Biology and Medicine 82:25-36.

Sinkule, J. A. 1984. Etoposide: A semisynthetic epipodophyllotoxin. Chemistry, pharmacology, pharmacokinetics, Adverse effects and use as an antineoplastic agent. Pharmacotherapy 4: 61–71.

Sklanskv, B. D., R.S. Mann-Kaplan, A.F. Reynolds Jr, M.L. Rosenblum, M.D. Walker. 2006. 4′-Demethyl-epipodophyllotoxin-β-D-thenylidene-glucoside (PTG) in the treatment of malignant intracranial neoplasms. Cancer 33: 460–467.

This paper was developed as part of the BIO 368 - Medical Botany course offered at Wilkes University during the summer of 2001. Course instructor was Kenneth M. Klemow, Ph.D. (kklemow@wilkes.edu). The information contained herein is based on published sources, and is made available for academic purposes only. No warrantees, expressed or implied, are made about the medical usefulness or dangers associated with the plant species in question.

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This page posted and maintained by Kenneth M. Klemow, Ph.D., Biology Department, Wilkes University, Wilkes-Barre, PA 18766. (570) 408-4758, kklemow@wilkes.edu.