Submitted to: Planta Medica
Publication Type: Peer reviewed journal
Publication Acceptance Date: 2/1/2000
Publication Date: N/A
Citation: Interpretive Summary: The lignan podophyllotoxin is a plant-derived natural product that is used for the production of certain anticancer drugs. The main commercial source of podophyllotoxin is a plant found in the Himalayas, Podophyllum emodii, which is in danger of extinction as a result of over-collection and lack of cultivation. Given the increasing medicinal importance of podophyllotoxin, alternative and renewable sources of this compound need to be developed. Rhizomes and leaves of the American mayapple, P. peltatum, have been found to contain up to 0.54% podophyllotoxin, along with varying amounts of related compounds. We describe here a new method for the extraction of podophyllotoxin that takes advantage of the presence of highly active and stable enzymes in dry tissues of P. peltatum. The new extraction method increases the yield of podophyllotoxin by over 300%, relative to that obtained by traditional extraction protocols. The leaves of P. peltatum can thus be a rich source of podophyllotoxin and may be used instead of the rhizomes, making the destruction of the plant unnecessary. Adoption of the new method may lead to the use of cultivated P. peltatum as the source of raw material.
Technical Abstract: A method has been developed for the extraction of podophyllotoxin from Podophyllum peltatum L. as part of ongoing efforts to find renewable sources of this compound. The new procedure consists of incubating the powdered plant material in dilute phosphate buffer prior to ethanol extraction. Using this procedure, rhizomes and leaves of P. peltatum yield at least 300% more podophyllotoxin than previously reported. The leaves of P. peltatum were found to be a richer source of podophyllotoxin than the rhizomes, yielding up to 1.9%, on a dry-weight basis. Large amounts of (- and (-peltatin were also obtained. The increased yield is the result of the action of highly stable (-glucosidases that retain their activity long after the plant tissues are dried, and become activated upon re-hydration of the material. In situ, the enzymes were equally active at various pH, and showed varying but generally little susceptibility to high temperatures, exposure to mild organic solvents, and dilute anionic detergent. Commercial application of the new method may make the sustainable cultivation of P. peltatum an economically viable alternative to the destructive collection from wild-growing populations.