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.
Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Jinan University, Huangpu Avenue West 601, Guangzhou 510632 (P.R. China).
Huan-Huan
HH
Zheng
Cui-Ting
CT
Luo
Heru
H
Chen
Juan-Na
JN
Lin
Chun-Ling
CL
Ye
Shuang-Shuang
SS
Mao
Yu-Lin
YL
Li
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use; D011485:Protein Binding; D029967:Swertia / Q000737:chemistry* / Q000378:metabolism; D044004:Xanthones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000737:chemistry / Q000378:metabolism
C574093:1,3,5,8-tetrahydroxyxanthone; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D044004:Xanthones; D006861:Hydrogen Peroxide; D000449:Aldehyde Reductase; D000520:alpha-Glucosidases
aldose reductases; antioxidants; diabetes; multitarget inhibitors; xanthones; α-glucosidases