Podophyllum (Podophyllum hexandrum, Podophyllum peltatum)

Category

Herbs & Supplements

Synonyms

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.

Background

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.

Evidence

DISCLAIMER: 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.
Grade: B

Leukoplakia (HIV-related): 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.
Grade: C

Rheumatoid arthritis: 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.
Grade: C

Uterine cancer: 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.
Grade: C

Tradition

WARNING: DISCLAIMER: The below uses are based on tradition, scientific theories, or limited research. 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 healthcare provider. There may be other proposed uses that are not listed below.
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).

Dosing

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.

Safety

DISCLAIMER: Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.

Allergies

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.

Interactions

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.

Attribution

This information is based on a systematic review of scientific literature, and was peer-reviewed and edited by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Jessica Clubb, PharmD (Northeastern University); Nicole Giese, MS (Natural Standard Research Collaboration); Erica Seamon, PharmD (Nova Southeastern University); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Wendy Weissner, BA (Natural Standard Research Collaboration); Lisa Wendt, PharmD (Albany College of Pharmacy).

Bibliography

DISCLAIMER: 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.

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.

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.

Frasca T, Brett AS, Yoo SD. Mandrake toxicity. A case of mistaken identity. Arch Intern Med 9-22-1997;157(17):2007-2009.

Goel HC, Prasad J, Sharma A, et al. Antitumour and radioprotective action of Podophyllum hexandrum. Indian J Exp Biol 1998;36(6):583-587.

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.

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.

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.

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.

Moraes RM, Bedir E, Barrett H, et al. Evaluation of Podophyllum peltatum accessions for podophyllotoxin production. Planta Med 2002;68(4):341-344.

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.

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.

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.

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.

Wollina U. Er:YAG laser followed by topical podophyllotoxin for hard-to-treat palmoplantar warts. J Cosmet.Laser Ther. 2003;5(1):35-37.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.