Study on gentiopicroside regulating the PPAR-γ/Nrf2 signaling pathway to improve oxidative damage in white adipose tissue of the type 2 diabetes mice

LONG Dongmei; ZHOU Maoting; LUO Siyao; LI Huijuan; PENG Xingcan; GUO Nan; WANG Xing

doi:10.13506/j.cnki.jpr.2026.02.004

Abstract：Objective To investigate the effect of gentiopicroside(GPS)on oxidative damage in white adipose tissue of type 2 diabetes mellitus(T2DM)mice and explore its underlying mechanism.Methods After a high-fat diet combined with streptozotocin(STZ)induced a T2DM model in C57BL/6J mice,the mice were randomly divided into a model group,a low-dose GPS group(25 mg·kg-1),and a high-dose GPS group(50 mg·kg-1),and another 10 C57BL/6J mice fed with normal diet were taken as the normal control group,and the drug was given orally once a day for 8 weeks.During the experiment,the basic metabolic indices of the mice were measured.When the mice were sacrificed,the serum and white adipose tissue were collected.Pathological staining was performed on the white adipose tissue.Lipid metabolism-related indices in the serum and oxidative stress-related indices in the white adipose tissue were measured.Western blotting was used to determine the protein expression of peroxisome proliferator-activated receptor γ(PPAR-γ)and nuclear factor E2-related factor 2(Nrf2)in the white adipose tissue.Results GPS significantly reduced the postprandial blood glucose(PBG),fasting blood glucose(FBG),food intake,and water intake in T2DM mice(P﹤0.01).It also significantly improved oral glucose tolerance abnor-malities(P﹤0.01)and enhanced insulin sensitivity in T2DM mice(P﹤0.01).GPS attenuated the pathological morphological abnormalities in white adipose tissue and lipid metabolism disorders in T2DM mice(P﹤0.01),and reduced the white fat weight and white fat index(P﹤0.01).GPS remarkably increased the activity of antioxidant enzymes and the contents of an-tioxidant substances(P﹤0.01),and markedly reduced malondialdehyde(MDA)content(P﹤0.01)in white adipose tissue.Furthermore,GPS increased the expression of PPAR-γ and Nrf2 proteins in white adipose tissue(P﹤0.01).Conclusion GPS may exert its anti-T2DM effect by alleviating oxidative damage in white adipose tissue through regulating the PPAR-γ/Nrf2 signaling pathway.