Scutellarin Exerts Hypoglycemic And Renal Protective Effects In Db/db Mice Via Nrf2/HO-1 Signaling Pathway

Diabetes mellitus is a metabolic disease characterized by defects in insulin secretion and hyperglycemia,and the number of diabetes patients in China currently ranks first in the world.Moreover,various medical treatments have side effects of varying degrees,and the treatment of insulin injection also makes patients suffer.Therefore,a safe and effective,low-pain diabetes treatment has become an urgent problem to be solved.SCU is a flavonoid compound extracted from Erigeron breviscapus,the molecular formula is C₂₁H₁₈O₁₂.According to reports,SCU has a variety of pharmacological activities,such as anti-oxidation,anti-inflammatory,neuroprotection and anti-tumor.However,there are few studies on the effect of SCU on diabetes.This article takes SCU as the research object,selects db/db mice as the animal model of diabetes,and db/m mice as the blank control,systematically analyzes and evaluates the possibility of developing SCU as a new drug for diabetes treatment and kidney protection,and further studies its Mechanism.SCU was given to db/db mice for 8 consecutive weeks by intragastric administration.The body weight and fasting blood glucose were measured and recorded every week during the experiment.The results showed that SCU treatment effectively reduced the body weight of db/db mice and Blood sugar level.Using metabolic cages to measure and analyze the food intake and water intake of mice,the results showed that the treatment of SCU successfully reversed the high level of food and water intake of db/db mice.Pathological section results showed that SCU reversed the pathological phenomena of lipid accumulation in hepatic vesicles of db/db mice,steatosis of hepatocytes,glomerular hypertrophy and irregular islet shape.The results of RT-PCR further verified the renal protection of SCU.SCU reduced the mRNA overexpression of kidney injury markers in the kidneys of db/db mice,including RAGE,NGAL and KIM-1,macrophage marker CD11b and T cell marker CD3.The results of cytokine determination experiments showed that the serum GHbA1c of db/db mice administered with SCU was significantly reduced.SCU administration also increased the serum INS level and PK activity in mice.This provides an experimental basis for the hypoglycemic effect of SCU.On the other hand,SCU also has a certain regulating effect on blood lipids in db/db mice:SCU administration restored the levels of TG and TCHO in the serum of db/db mice to normal levels,and HDL-C levels were significantly increased.Combined with the results of antibody chip measurement,it was found that SCU can exert inflammation inhibitory effects by reducing the levels of proinflammatory cytokines GSK,ICAM-2 and IL-1?and IL-2,and increasing the level of inflammation-inhibiting cytokine IL-4.In addition,SCU reduced the concentration of ROS and MDA in the serum and kidney of db/db mice,and increased the levels of SOD,GSH-Px and CAT.Western blot results showed that SCU up-regulated the expression of Nrf2,thereby increasing the expression levels of HO-1,SOD1 and SOD2,and CAT in the kidney.Comprehensive experimental results found that SCU may play a role in lowering blood sugar and protecting kidneys in db/db mice by regulating the Nrf2/HO-1 signaling pathway.