3β-Hydroxy-5,16-Pregnadien-20-One Exhibits both Hypolipidemic and Hypoglycemic Activities

The increasing incidence of disorders due to metabolic syndrome, which include hyperlipidemias, diabetes and hypertension, has taken serious dimension world over, including in India, and has become a matter of deep concern. Drugs which can inhibit more than one disorder of this syndrome would add much therapeutic value to its management. 3β -Hydroxy-5,16- pregnadien-20-one (80-574, 2), selected based on the structural lead of the presence of a β -enone pharmacophore in/around ring D of Guggulsterone (1), the main active constituent of the phytopharmaceutical Gugulip developed at CDRI, Lucknow from the Ayurvedic herbal drug Gum Guggul, has been found to exhibit both hypolipidemic and hypoglycemic activities in the conventional experimental animal models used for studying these activities. In mode of hypolipidemic action studies in high fat diet-fed rats, compound 80-574 was found to enhance lipolysis of serum lipoproteins, enhance the uptake of LDL by hepatocyte membranes, indicating increased catabolism of LDL, and caused increased faecal excretion of bile acids indicating enhanced mobilization of cholesterol from fatty deposits. Compound 80-574 also exhibited antioxidant activity in in vitro and in vivo experimental models, and protected LDL against oxidation, indicating protection against atherogenesis. Compound 80-574 also exhibited moderate inhibition of cholesterol biosynthesis in liver slices. Treatment with 80-574 also improves glucose tolerance in diabetic rats. With these multiple sites of hypolipidemic action accompanied with its hypoglycemic activity, compound 80-574 appears a promising candidate for the treatment of dyslipidemias and diabetes and thus for management of metabolic syndrome. A synoptic view of the various functional activities exhibited by compound 80-574 is presented in this article.