Coagulanolide, a withanolide from Withania coagulans fruits and antihyperglycemic activity

One new withanolide, (17S,20S,22R)-14alpha,15alpha,17beta,20beta-tetrahydroxy-1-oxowitha-2,5,24-trienolide) named coagulanolide (4) along with four known withanolides 1-3 and 5 have been isolated from Withania coagulans fruits and their structures were elucidated by spectroscopic techniques. The compounds 1-5 showed significant inhibition on postprandial rise in hyperglycemia post-sucrose load in normoglycemic rats as well as streptozotocin-induced diabetic rats. The compound 5 also showed significant fall on fasting blood glucose profile and improved the glucose tolerance of db/db mice. Further compound 5 showed antidyslipidemic activity in db/db mice. The median effective dose of the compound 5 was determined to be around 25 mg/kg in streptozotocin-induced diabetic rats, which is comparable to the standard antidiabetic drug metformin. Our results provide further support to explain the traditional use of W. coagulans as antihyperglycemic cum antidyslipidemic agent by the traditional medical practitioners.