Nephroprotective Effect of Equol in Type 2 Diabetic Rats

Type 2 diabetes mellitus (T2DM) is a chronic disease caused by insufficient or inefficient use of insulin, which is commonly seen in adults and is also called adult-onset diabetes mellitus, and its typical symptoms are known as "three more and one less", which refers to drinking more, eating more, urinating more, and weight loss. Type 2 diabetes is a disease with high morbidity and mortality worldwide. Long-term hyperglycemic state, insulin resistance, and metabolic disorders can cause various acute and chronic organ damage in the body. Diabetic kidney disease (DKD) is one of the important complications of diabetes mellitus, the incidence of which is on the rise in China, and has now become the second cause of end-stage renal disease (ESRD)]. Due to the strong renal reserve function, the early symptoms of patients with T2DM complicating renal injury are not obvious, and once clinical symptoms such as proteinuria appear, the renal microstructure has been severely diseased and difficult to reverse, and the treatment is difficult and the prognosis is poor.Therefore, it is important to start the prevention and treatment of T2DM renal injury at an early stage. Equol, a major metabolite of the plant phytoestrogen soy isoflavone genistein, mimics estrogenic effects in vivo, exerting various biological effects such as antioxidative stress and anti-inflammatory responses. It avoids estrogen's side effects. To explore its renal protective effects on type 2 diabetic rats and its impact on renal tissue oxidative stress and inflammatory cytokine levels, experimenters chose 6-week-old SD rats. They were divided into control and T2DM model groups, with the model group further divided into different doses of Equol intervention groups. After 12 weeks of continuous intervention, renal function and nuclear factor E2 in renal tissues were assessed.

In summary, it was shown that serum urea nitrogen (BUN), serum creatinine (CREA) and uric acid (UA) levels were significantly reduced in the Equol intervention group compared with that of the model group, and the levels of MDA,TNFα､IL-6 and IL-1β in the renal tissues were significantly lower than that of the model group, and the microstructures of renal tissues were significantly improved compared with that of the model group, and the expressions of total Nrf2, nuclear Nrf2 and HO-1 proteins were significantly increased compared with that of the model group. The microstructure of renal tissue was significantly improved compared with that of the model group, the total Nrf2, nuclear Nrf2 and HO1 protein expression of renal tissue was significantly increased compared with that of the model group, and the levels of and HO-1 mRNA of renal tissue were significantly higher than that of the model group.

The results showed that Equol was able to decrease the production of Nrf2, inhibit nitric oxide, and inhibit nitric oxide production of Nrf2, Nrf2 and HO-1 mRNA in lipopolysaccharide-induced peritoneal adherent cells and in vitro-cultured RAW264.7 cells. The results showed that estragole can reduce the production of nuclear factor κB in lipopolysaccharide-induced peritoneal adherent cells and RAW264.7 cells in vitro culture, inhibit the expression of nitric oxide synthase gene, reduce the level of nitric oxide, and exert antioxidant and anti-inflammatory effects; estragole can significantly reduce the damage of renal tissues in T2DM rats and help improve renal function; estragole can also significantly reduce the oxidative stress and inflammation in renal tissues of T2DM rats, and increase the antioxidant capacity of renal tissues, thus exerting renal protective effects and slowing down the onset and progression of diabetic renal injury.

参考:

[1] https://baike.baidu.com/item/2%E5%9E%8B%E7%B3%96%E5%B0%BF%E7%97%85/5372831

[2] 沈鑫,程庆砾. 糖尿病与急性肾损伤关系的研究进展[J]. 国际移植与血液净化杂志,2022,20(06)：1-5.

[3] 雌马酚对２型糖尿病大鼠的肾脏保护作用[J].李 硕，倪向敏，徐喆，张贵明，崔涵强，王 建400037重庆，陆军军医大学（第三军医大学）第二附属医院.营养科. DOI:10.16016/j.20970927.202110145