Podophyllum

Podophyllum peltatum, more commonly known as the mayapple, belongs to the family Berberidaceae (Barberry). Its name is derived from its structure and literally means "foot leaf plant with umbrella-shaped leaves". A young mayapple resembles an umbrella because of its single stem with one or two large, rounded leaves trailing down, while an older mayapple usually consists of a single stem that branches into two, each with one or two large, rounded leaves trailing down, and a flower growing in the fork with a thin stalk and 6-9 white petals. This plant is a native to Northern American woods.

The stems grow to 30–40 cm tall, with palmately lobed umbrella-like leaves up to 20–40 cm diameter with 3–9 shallowly to deeply cut lobes. The plants produce several stems from a creeping underground rhizome; some stems bear a single leaf and do not produce any flower or fruit, while flowering stems produce a pair or more leaves with 1–8 flowers in the axil between the apical leaves. The flowers are white, yellow or red, 2–6 cm diameter with 6–9 petals, and mature into a green, yellow or red fleshy fruit 2–5 cm long.

All the parts of the plant, excepting the fruit, are poisonous. Even the fruit, though not dangerously poisonous, can cause unpleasant indigestion.

The substance they contain(podophyllotoxin or podophyllin) is used as a purgative and as a cytostatic.Posalfiin is a drug containing podophyllin and salisalic acid that is used to treat the planter wart.

Kingdom:

Plantae

Division:

Magnoliophyta

Class:

Magnoliopsida

Order:

Ranunculales

Family:

Berberidaceae

Genus:

Podophyllum
L.

   Historically, this plant was widely used as a Chinese herbal medicine because it is a wild Asian plant (Becker, 2000). It was used to treat snakebites, general weakness, poisons, condyloma accuminata, lymphadenopathy, and certain tumors (Chang, et al, 1992). It was also used by the Penobscot Indians to treat cancer (Duke, 1995). In the early 19th century, it was used as a laxative, a liver cleanser, and a treatment for syphilis (Cures from the Earth 1991, Chang, et al 1992).

Chemical analysis of the mayapple reveals the presence of several lignans, which has been shown to have anti-cancer effects. The starting material of etoposide (Vepeside), an FDA approved cancer drug, is podophyllum and has been used to treat testicular cancer as well as small-cell lung cancer by inhibiting replication of cancer cells (Dickson 1995, Becker 2000, Henderson 2000). Scientists are using a new extraction method and intend to continue and perfect the use of the mayapple in anti-cancer drugs (Becker, 2000).

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 Besides this, it also shows antiviral activities by interfering with some critical viral processes. Availabilityof podophyllotoxin from plants has its limitations because of its intense collection from nature and lack of organized cultivation. The chemical synthesis of podophyllotoxin is considered to be very complicated as yet. The use of biotechnological approaches for the production of podophyllotoxin using cell cultures, organ cultures, and biotransformation route or by manipulating biosynthetic pathway proves to be an attractive alternative for production of podophyllotoxin.

Safety

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.

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.

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.

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 forgenital 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 rheumatoi 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

1. 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. 

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ishit r kothari

ishit r kothari (show bio)