Xanthones from Swertia mussotii as multitarget-directed antidiabetic agents.

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 IC50 values of 5.2±0.3 μM and 88.6±1.6 nM, 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.