Effect Of Curcumin And Its Analogues On The Expression Of Inflammatory Factors In Brain Tissue Of Diabetic Mice

Object:This study was to investigate the effect of curcumin and its analogues H8 on the expression of inflammatory factors in the brain of type 2 diabetic mice,and to provide experimental evidence for the treatment of diabetic encephalopathy.Methods : The experiment was divided into two parts: the first part is the cell experiment.The cytotoxicity of curcumin and its analogue H8 was detected by CCK-8 method.Lipopolysaccharide(LPS)-induced monocyte-macrophage(j774a.1)was used to construct the inflammatory cell model,and intervened by curcumin or H8,the mRNA levels of TNF-? and IL-6 were tested by qPCR.the secretion levels of TNF-? and IL-6 in culture supernatant were detected by ELISA.The second part is animal experiments,the experiment was divided into five groups: db/m mice were used as a control group,db/db mice in other treatment groups,including diabetic group,Curcumin group(curcumin,5 mg/ kg),H8-L group(h8-l,5 mg/ kg)and H8-H group(h8-h,10 mg/ kg).Except for control group and diabetic group.The mice were fed with curcumin and H8 for 8 weeks.The control group and the diabetic group were fed the same volume of saline at the same time.After 8 weeks,Morris water maze was used to detect the Learningand Memory ability.HE staining and immunohistochemistry were used to detect the morphological changes of brain tissue and the expression of TNF-?,IL-6 and IL-17 in mice.Results:1.H8 had almost no cytotoxicity in the experimental concentration range,and the curcumin had significant cytotoxicity at about 40 ?mol/L,and the cell survival rate was significantly lower than that of the control group(P<0.001).2.Both Curcumin and H8 were able to inhibit the expression of TNF-? and IL-6,among which H8 had better inhibitory effect on inflammatory cytokines than curcumin.3.Compared with the diabetic group,the escape latency of the H8 group was significantly shorter than that of the diabetic group,and the shortened H8 group was more obvious and the number of crossing the platform increased significantly(P<0.05).4.HE staining showed that the brain tissue of diabetic group had obvious pathological changes,and the pathological morphology of brain tissue was improved after high dose of H8 treatment.5.Immunohistochemical staining showed that compared with diabetes groups,the levels of IL-6,TNF-? and IL-17 in brain tissue of curcumin group(5 mg/kg)and high dose H8 group(10 mg/kg)were significantly decreased.(P<0.05,P<0.01)Conclusions:Curcumin and its analogues H8 are able to inhibit the expression of inflammatory factors to play a significant anti-inflammatory effect,in which H8 anti-inflammatory effect is more obvious.And both of them can improve the learning and memory ability of diabetic mice,in which the role of high concentration of H8 more obvious.