Bile acids: Can the position of hydroxyl substitution influence antidiabetic potency?

Abstract Numerous analogous compounds exist in natural products, exhibiting subtle structural variations that nonetheless result in distinct biological activities. Hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), and deoxycholic acid (DCA) are analogues belonging to the steroids, and related studies have demonstrated that all three possess antidiabetic effects in reducing hyperglycemia. Diabetes mellitus is a metabolic disease with high morbidity and mortality in recent years. A thorough exploration of the mechanisms underlying compounds with potential antidiabetic properties serves as an essential prerequisite for subsequent research endeavors. However, the mechanism of action regarding them has not been fully verified, and the present study identified one of the antidiabetic mechanisms of action of bile acid analogs at the protein and molecular levels. The results suggested that structural differences due to differences in the position of the hydroxyl substituent alter the antidiabetic capacity. The application of machine learning methods for pharmacokinetic prediction contributes to a better understanding of the nature and in vivo behavior of bile acid analogs. This study endeavors to establish a basic reference and experimental foundation to contribute to the ongoing exploration of the potential role of bile acid compounds in antidiabetic mechanisms.