Guggulsterone: a Potent Natural Hypolipidemic Agent from Commiphora wightii – Problems, Perseverance, and Prospects

Abstract

Two isomers of guggulsterone, -E and -Z, have been established as bioactive molecules responsible for the lipid- and cholesterol-lowering activities of oleogum-resin of Commiphora wightii (Arnott.)Bhandari (syn. C. mukul). Guggulsterone is a safe and effective natural product for hypercholesterolemia that has been used as such for the past 3000 years in Ayurveda. It is obtained from a very slow growing desert tree endemic to the Thar Desert and has become endangered due to its over exploitation. Oleogum-resin is a complex mixture of several classes of compounds including gum, minerals, essential oils, sterols, flavanones, and sterones. Early chemical and pharmacological work was carried out in India, but after approval by the United States Food and Drug Administration as a food supplement, several reports describe a role for guggulsterone in the excretion of cholesterol, involving the farnesoid X receptor, pregnane X receptor, Cyp-7A1 gene, and the bile salt export pump. Biotechnological approaches have been made to develop micropropagation methods through axillary bud break and somatic embryogenesis, as well as guggulsterone production through cell cultures grown in shake flasks and bioreactors. Field-grown plants show genetic variations, as evident by randomly amplified polymorphic DNA fingerprinting. This review summarizes the research already carried out and that needs to be done to elucidate the biosynthetic pathway, mechanism of action, and biotechnological production of guggulsterone through cell cultures before commercialization of the molecule as a drug.