Study of Genetic Variations in Podophyllum Hexandrum and Computational Screening of Podophyllotoxin Analogues

Abstract

Podophyllum hexandrum Royle (Berberidaceae), more popularly known as Indian Mayapple is a herbaceous, rhizomatous species of great medicinal importance. It has long been used by the Himalayan natives and the American Indians. The rhizomes of several Podophyllum species have been found to be the source of podophyllotoxin, 4 -demethyl podophyllotoxin and podophyllotoxin 4-O-glucoside. These compounds have been used for the treatment of lung and testicular cancers as well as certain types of leukemia. Podophyllotoxin is also the precursor of semi synthetic chemotherapeutic drugs such as etoposide, teniposide and etophos. The Indian species P. hexandrum contains three times more podophyllotoxin than its American counterpart P. peltatum. The rhizomes are being indiscriminately harvested in large quantities from the wild to meet the ever increasing demand for the crude drug. As a result of this and a lack of organized cultivation, P. hexandrum has been reported as a threatened species in the Himalayan region. Some of the populations in certain pockets have virtually disappeared owing to anthropogenic activities and overexploitation. As the species is already endangered and exploitation of its underground parts continues to exceed the rate of natural regeneration, it needs immediate attention for conservation. Studies of its population biology and genetic diversity are important for successful development of conservation strategies. Podophyllotoxin content varies greatly between populations of P. hexandrum from the Northwestern Himalayas. Therefore, it would be inefficient, environmentally destructive and economically unsound to randomly harvest Mayapple. For the rapid development of P. hexandrum as an economically viable alternative crop, it would be essential to evaluate the natural populations of P. hexandrum for podophyllotoxin content and agronomic traits in the Himalayan region.