Podophyllum (Podophyllum hexandrum, Podophyllum peltatum)
Natural Standard Bottom Line Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.
While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.
American mandrake, Araceae (family), bajiaolian, Berberidaceae (family), beta-peltatin, Condylox®, devil's apple, diphyllin, duck's foot, Dysosma pleianthum, epipodophyllotoxin, etoposide 7a, etophos 7b, ground lemon, Hakkakuren, highly purified podophyllotoxin, Himalayan mayapple, hog apple, Indian apple, Indian podophyllum, kampherol, mandrake, mayapple, Podocon-25®, podofilox, Podofin®, podophylli pelati rhizome/resina, podophyllic acid, podophyllin, podophyllinic acid ethylhydrazide, podophyllotoxin, podophyllotoxin-beta-o-benzyliden-glucoside (SP-G), podophyllotoxin derivatives, Podophyllum emodi, Podophyllum hexandrum, Podophyllum hexandrum Royale, podophyllum lignan, Podophyllum peltatum, Podophyllum peltatum L., Podophyllum pleianthum, podophyllum resin, Podophyllum versipelle, Proresid®, quercetin, raccoon berry, semisynthetic podophyllotoxin glycosides, Sinopodophyllum emodi, Syngonium podophyllum, umbrella plant, vegetable mercury, wild lemon, wild mandrake.
Note: Podophyllum should not be confused with Mandragora officinarum, although both are commonly known as mandrake. Podophyllum is potentially toxic when orally ingested.
Podophyllum gets its name from the Greek words podos and phyllon, meaning foot shaped leaves. Podophyllum rhizomes have a long medicinal history among native North American tribes who used a rhizome powder as a laxative or an agent that expels worms (anthelmintic). A poultice of the powder was also used to treat warts and tumorous growths on the skin.
Podophyllotoxin is a plant-derived compound used to produce two cytostatic drugs, etoposide and teniposide. The substance has been primarily obtained from the American mayapple (Podophyllum peltatum). The Himalayan mayapple (Podophyllum hexandrum or Podophyllum emodi) contains this constituent in a much greater quantity, but is endangered in the wild.
Currently, extracts of the podophyllum plant are used in topical medications for genital warts, HIV-related oral hairy leukoplakia, and some skin cancers. Preliminary research also shows that CPH 82, an oral form of Podophyllum emodi composed of two purified semisynthetic lignan glycosides, may be useful in treating rheumatoid arthritis. However, when used orally, podophyllum can be lethal and should be avoided. The drug etoposide (VePesid®) is the semisynthetic derivative of podophyllotoxin, and is approved by the U.S. Food and Drug Administration (FDA) for various types of cancer.
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Warts (genital warts, plantar warts)
Podofilox, an active component of podophyllin resin, is marketed under the brand name Condylox® and is approved by the U.S. Food and Drug Administration (FDA) for the treatment of external genital warts and perianal warts. Preliminary study showed that podophyllum preparation was moderately effective in the treatment of genital warts. Additional study is needed before a firm conclusion regarding efficacy can be made.
Oral hairy leukoplakia is an oral mucosal disease associated with the Epstein-Barr virus (EBV). Podophyllum and its derivatives are known to be active cytotoxic agents, which may be beneficial in the treatment of hairy leukoplakia. Additional study is needed before a firm conclusion regarding efficacy can be made.
Preliminary research suggests that podophyllum may be helpful for rheumatoid arthritis. Research is limited due to the possible adverse effects like severe diarrhea associated with taking podophyllum by mouth. However, additional research is needed before a firm conclusion can be drawn.
Preliminary evidence suggests that podophyllum may inhibit the growth of cancer cells, and may be beneficial as an adjunct to radiation for uterine cancer. Further research is needed before a strong recommendation can be made.
*Key to grades:A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.
Abortifacient (induces abortion), anthelmintic (expels parasitic worms), anti-bacterial, breast cancer, cathartic (relieves constipation), emetic (induces vomiting), fertility, fever, hepatitis, Hodgkin's disease, insecticide, jaundice, laxative, leukemia, liver disorders, mental disorders, non-Hodgkin's lymphoma, skin wounds, snake venom antidote, syphilis, tinea capitis (ringworm).
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Adults (18 years and older):
Various doses have been studied with varying degrees of safety and efficacy. For rheumatoid arthritis, 300 milligrams of CPH 82, composed of two purified semisynthetic lignan glycosides of Podophyllum emodi, has been taken daily and used safely for up to 12 weeks.
When used topically and appropriately, podophyllum has been used safely for up to five weeks. For genital warts, 5 milliliters of 0.5% podophyllin applied on the affected area twice daily, three days a week for five weeks has been used; a 2% podophyllin preparation has also been applied topically to the affected area twice daily, three days a week for five weeks. For HIV-related hairy leukoplakia, topical podophyllum resin 25% solution for 30 days has been used.
Children (younger than 18 years):
There is no proven safe or effective dose for podopyllum in children.
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Avoid in individuals with a known allergy or hypersensitivity to podophyllum.
Side Effects and Warnings
Podophyllum applied on the skin for genital warts and oral hairy leukoplakia appears to be well-tolerated. Generally mild adverse effects include burning sensation, bad or altered taste, and mild pain to severe irritation in topical application. Adverse effects from ingestion by mouth may include gastrointestinal discomfort (diarrhea and abdominal pain).
Systemic absorption of podophyllum resin may result in tachycardia (increased heart rate), hypotension (low blood pressure), hallucinations, confusion, dizziness, and convulsions. These symptoms may be delayed in onset and prolonged in duration. Podophyllum may also cause nausea, vomiting, bloody-watery diarrhea, and a diminished number of neutrophils in the blood (neutropenia). Use cautiously in patients with Crohn's disease or irritable bowel syndrome (IBS).
Podophyllum toxicity may cause muscle paralysis, ataxia (loss of coordination), urinary retention, renal (kidney) failure, and hypotonia (decreased muscle tone). Chronic use of podophyllym as a cathartic (relieves constipation) may cause abnormally low potassium concentrations in the blood (hypokalemia) and metabolic alkalosis.
Podophyllotoxin solution (Wartec®) may cause sweaty palms and feet or rash. Alopecia (hair loss) and gastrointestinal toxicity (nausea, vomiting, stomatitis) has occurred in about 20-30% of patients given recommended dosages of etoposide, a semi-synthetic derivative of podophyllotoxin. Patients receiving oral CPH 82 for rheumatoid arthritis reported gastrointestinal discomfort (diarrhea and abdominal pain).
Use cautiously in patients with cardiovascular, muscular, and neurologic disorders, renal (kidney) insufficiency, liver insufficiency, hypertension (high blood pressure), arrhythmia (abnormal heart rate), or psychosis.
Avoid in patients with gallbladder disease or gallstones. Podophyllum is believed to stimulate the production of bile in the gallbladder.
Pregnancy and Breastfeeding
Podophyllum is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence. Documented cases of birth defects and fetal deaths have been associated with podophyllum used during pregnancy.
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.
Interactions with Drugs
Podophyllum toxicity may cause additive hypotension (low blood pressure) if administered with antihypertensive medications.
Podophyllum interrupts cellular mitosis at metaphase. Podophyllum may interact with drugs that have a similar mechanism, such as paclitaxel, vincristine. Additionally, anticancer agents may cause neutropenia (diminished number of neutrophils in the blood). Concurrent use of podophyllum and antineoplastic agents may cause further bone marrow suppression.
Podophyllum toxicity may cause a worsening of extrapyramidal symptoms that may occur with antipsychotic agents. Caution is advised when taking podophyllum with other agents that could potentiate these symptoms.
Although not well studied in humans, degenerative changes were observed in the liver after ingestion of podophyllum. Caution is advised when taking podophyllum with other potentially liver damaging agents due to the increased risk of liver damage.
Podophyllum has been historically used as a laxative. Concurrent use of podophyllum and other laxatives may result in an additive effect and cause dehydration and electrolyte disturbances (usually fluid depletion and accumulation of electrolytes).
Interactions with Herbs and Dietary Supplements
Podophyllum toxicity may cause additive hypotension (low blood pressure) if administered with antihypertensive (blood pressure lowering) herbs and supplements.
Podophyllum may interrupt mitosis and prevent cell division. Additionally, anticancer agents may cause neutropenia (shortage of white blood cells). Concurrent use of podophyllum and anticancer agents may cause an increase in neutropenia (shortage of white blood cells).
Podophyllum toxicity may cause a worsening of extrapyramidal symptoms and neurologic side effects that may occur with some antipsychotic agents. Caution is advised when taking podophyllum with herbs or supplements that could potentiate these symptoms.
Although not well studied in humans, degenerative changes were observed in the liver after ingestion of podophyllum. Caution is advised when taking podophyllum with other potentially liver damaging herbs due to the increased risk of liver damage.
Podophyllum has been historically used as a laxative. Concurrent use of podophyllum and other laxatives may result in an additive effect and cause dehydration and electrolyte disturbances.
This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.
Agrawala PK, Mittal A, Bala M, et al. Mitochondrial involvement in RP-1 mediated apoptosis in U 87 cells. Biomed.Pharmacother. 2004;58(2):129-135. View Abstract
Camporese A, Balick MJ, Arvigo R, et al. Screening of anti-bacterial activity of medicinal plants from Belize (Central America). J Ethnopharmacol. 2003;87(1):103-107. View Abstract
Chattopadhyay S, Bisaria VS, Panda AK, et al. Cytotoxicity of in vitro produced podophyllotoxin from Podophyllum hexandrum on human cancer cell line. Nat.Prod.Res. 2004;18(1):51-57. View Abstract
Frasca T, Brett AS, Yoo SD. Mandrake toxicity. A case of mistaken identity. Arch Intern Med 9-22-1997;157(17):2007-2009. View Abstract
Goel HC, Prasad J, Sharma A, et al. Antitumour and radioprotective action of Podophyllum hexandrum. Indian J Exp Biol 1998;36(6):583-587. View Abstract
Gupta D, Arora R, Garg AP, et al. Radiation protection of HepG2 cells by Podophyllum hexandrum Royale. Mol.Cell Biochem. 2003;250(1-2):27-40. View Abstract
Kumar IP, Goel HC. Iron chelation and related properties of Podophyllum hexandrum, a possible role in radioprotection. Indian J Exp Biol 2000;38(10):1003-1006. View Abstract
Longstaff E, von Krogh G. Condyloma eradication: self-therapy with 0.15-0.5% podophyllotoxin versus 20-25% podophyllin preparations--an integrated safety assessment. Regul.Toxicol.Pharmacol 2001;33(2):117-137. View Abstract
Mittal A, Pathania V, Agrawala PK, et al. Influence of Podophyllum hexandrum on endogenous antioxidant defence system in mice: possible role in radioprotection. J Ethnopharmacol. 2001;76(3):253-262. View Abstract
Moraes RM, Bedir E, Barrett H, et al. Evaluation of Podophyllum peltatum accessions for podophyllotoxin production. Planta Med 2002;68(4):341-344. View Abstract
Prakash H, Ali A, Bala M, et al. Anti-inflammatory effects of Podophyllum hexandrum (RP-1) against lipopolysaccharides induced inflammation in mice. J Pharm Pharm Sci 2005;8(1):107-114. View Abstract
Prem Kumar I, Rana SV, Samanta N, et al. Enhancement of radiation-induced apoptosis by Podophyllum hexandrum. J Pharm Pharmacol 2003;55(9):1267-1273. View Abstract
Triantos D, Porter SR, Scully C, et al. Oral hairy leukoplakia: clinicopathologic features, pathogenesis, diagnosis, and clinical significance. Clin Infect.Dis. 1997;25(6):1392-1396. View Abstract
White DJ, Billingham C, Chapman S, et al. Podophyllin 0.5% or 2.0% v podophyllotoxin 0.5% for the self treatment of penile warts: a double blind randomised study. Genitourin.Med 1997;73(3):184-187. View Abstract
Wollina U. Er:YAG laser followed by topical podophyllotoxin for hard-to-treat palmoplantar warts. J Cosmet.Laser Ther. 2003;5(1):35-37. View Abstract
Copyright © 2013 Natural Standard (www.naturalstandard.com)
The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
March 22, 2017