Sesquiterpenoids from antidiabetic Psacalium decompositum block ATP sensitive potassium channels

The hypoglycemic effect of root and rhizome aqueous decoction of Psacalium decompositum (Asteraceae), a medicinal herb from Mexico, has been experimentally demonstrated, leading to the identification of several hypoglycemic sesquiterpenoids, such as cacalol, and the mixture of 3-hydroxycacalolide, and epi-3-hydroxycacalolide; however, the mechanism of action of these compounds is unknown.

To establish whether cacalol, cacalone epimer mixture and cacalol acetate may block adenosine triphosphate-sensitive potassium channels (K(ATP) channels) in a similar way to the antidiabetic drug glibenclamide.

Cacalol, cacalone epimer mixture, and cacalol acetate were tested on the diazoxide-induced relaxation of male rat aortic rings precontracted with phenylephrine (3.2x10(-6)M).

Cacalol (10(-5)M), cacalol acetate and the cacalone epimer mixture (10(-4)M) inhibited the diazoxide effect, in a similar manner and concentration as glibenclamide (10(-5)M). Cacalone epimer mixture exerted this effect in a concentration-dependent manner (P<0.01). Cacalol (10(-4)M), irreversibly inhibited the diazoxide-induced relaxation, and displayed activity at a lower concentration (10(-5)M) than cacalone epimer mixture and cacalol acetate.

These results suggest that the studied compounds block K(ATP) channels in a similar way to glibenclamide in rat aorta. However, controversial data indicate that Psacalium decompositum sesquiterpenoids are less effective than glibenclamide in lowering plasma glucose levels, suggesting that cacalol and cacalone epimer mixture, as well as cacalol acetate, may display a higher affinity to SUR2 subunit of K(ATP) channels in aortic smooth muscle than to SUR1 subunit in pancreatic beta-cells.