Xanthones from <i>Swertia mussotii</i> as Multitarget‐Directed Antidiabetic Agents

Abstract

Abstract Oxidative stress has been suggested to play a causative role in the development of obesity‐induced insulin resistance and type 2 diabetes. Given the antioxidant potency of previously reported xanthones isolated from Swertia mussotii . These natural products were further evaluated against other targets in diabetes, aldose reductase and α‐glucosidase, in order to identify novel multitarget‐directed antidiabetic agents. Among the 14 xanthones screened, 1,3,7,8‐tetrahydroxyxanthone ( 6 ), 1,3,5,8‐tetrahydroxyxanthone ( 7 ), and 2,3,6,8‐tetrahydroxyxanthone‐7C‐(β‐ D ‐glucoside) ( 12 ) were confirmed as good antioxidants and α‐glucosidase inhibitors. Xanthone 7 was also confirmed as a potent inhibitor of aldose reductase (ALR2). Xanthone 7 was the most active α‐glucosidase and ALR2 inhibitor, with IC 50 values of 5.2±0.3 μ M and 88.6±1.6 n M , respectively, while compound 12 was shown to be the most active antioxidant. Given the overall profile, xanthone 7 is considered to be the most promising multitarget antidiabetic agent, and may have potential for the treatment of both diabetes and diabetic complications.