Mulberry Leaf Flavonoids Inhibit Liver Inflammation in Type 2 Diabetes Rats by Regulating TLR4/MyD88/NF- κB Signaling Pathway

Abstract

The incidence of liver-related complications in type 2 diabetes mellitus (T2DM) is rapidly increasing, which affects the physical and mental health of T2DM patients. Mulberry leaf flavonoids (MLF) were confirmed to have certain effects on lowering blood glucose and anti-inflammation. In this study, the high-fat diet (HFD) + STZ method was used to establish T2DM rat model and the MLF was administered by gavage for eight weeks. During the experiment, body weight and blood glucose level were measured at different time points. The pathological changes of rat liver were observed by H&E staining. The serum glucolipid metabolic indicators of serum, fasting insulin (FINS), and inflammatory factors levels were detected by ELISA. The expression levels of toll-like receptor 4 (TLR4), TNF receptor-associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF- κB alpha (I κΒα), p-I κΒα, and nuclear factor kappa-B (NF- κB)/p65 protein in liver tissue were measured by Western Blot. After 8 weeks' MLF treatment, the blood glucose of rats showed a downward trend; glycolipid metabolism level and insulin resistance were improved, which suggested that MLF could improve the disorder of glucose and lipid metabolism. The pathological damage and inflammation of the liver in T2DM rats were significantly improved, the levels of related serum inflammatory factors were reduced, and the expression of liver tissue-related proteins was downregulated. Our results indicated that MLF could reduce blood glucose and inhibit the development of liver inflammation. The mechanisms may be associated with the activation of TLR4/MyD88/NF- κB signal pathway to reduce the levels of inflammatory factors in serum.