Wushenziye Formula Inhibits Pancreatic β Cell Apoptosis in Type 2 Diabetes Mellitus via MEK‐ERK‐Caspase‐3 Signaling Pathway

Abstract

Background Wushenziye formula (WSZYF), composed of Radix Polygoni Multiflori Preparata, Mori fructus, Mori folium, and Cassiae semen, is effective in the treatment of type 2 diabetes mellitus (T2DM). Aim In this study, we aimed to explore the effects and the underlying mechanisms of WSZYF on inhibiting pancreatic β cell apoptosis and improving insulin resistance (IR) in T2DM. Methods A T2DM model was induced by Goto-Kakizaki diabetes prone rats. Cell apoptosis model was induced in MIN6 cells. Results In vivo, WSZYF decreased fasting blood glucose (FBG), insulin concentration, insulin resistance index, triglyceride (TG), total cholesterol (TC), and free fatty acids (FFA) in T2DM rats. Meanwhile, WSZYF ameliorated impairments in the morphology and structure of pancreatic tissues. In vitro, WSZYF enhanced cell viability and promoted insulin secretion in the apoptosis model of MIN6 cells. Furthermore, WSZYF modulated the expressions of apoptosis-related molecules by increasing the expressions of MEK1/2, p-MEK1/2, ERK1/2, and p-ERK1/2 and decreasing the cleaved-caspase-3 expression. Conclusion These findings indicate that WSZYF may become a new drug candidate in the treatment of T2DM and its antidiabetic mechanism is probably inhibiting pancreatic β cell apoptosis by modulating the MEK-ERK-Caspase-3 signaling pathway.

Prevention of Oxidative Stress-Induced Pancreatic Beta Cell Damage by Broussonetia kazinoki Siebold Fruit Extract via the ERK-Nox4 Pathway

“…Horiuchi Y et al reported that the Erk pathway plays an important role in regulating cell proliferation, differentiation, and apoptosis [51]. In addition, reduction in Erk pathway signaling has been reported to inhibit beta cell apoptosis [52], and specific blockade of the Erk pathway improves insulin resistance in diabetic mice [53]. Previous reports including our results suggested that the activation of Erk is a critical step in the regulation of STZ-or angiotensin II-induced Nox4 expression [54,55].…”

Total Astragalus saponins can reverse type 2 diabetes mellitus-related intestinal dysbiosis and hepatic insulin resistance in vivo

“…Dysregulation of glycogen synthesis or glucogenesis and increased gluconeogenesis caused by hepatic IR are the main causes of fasting hyperglycemia in T2DM patients ( 56 – 58 ). This in turn causes glucotoxicity and impairs islet structure and function ( 59 ). INS in the liver binds to the INS receptors tyrosine kinases, phosphorylates IRS-1, and activates the AKT, thereby decreasing hepatic glucose production and promoting glycogen synthesis.…”

Taraxacum officinale Extracts Alleviate Anhedonia and Depression by Inhibiting UPRmt and Mitophagy in the Hippocampi of T2DM Rats

“…After 6 weeks, the rats were allowed to fast for 12 h. Then streptozotocin (STZ), 28 mg/kg of body weight was injected intraperitoneally to induce T2DM (Zhang et al, 2019). Rats with fasting plasma glucose (FPG) ≥11.1 mmol/L (Tian et al, 2018) and reduced sucrose preference rate (SPR) were randomly divided into three groups: model group (MG) [ n = 6], metformin treatment group (MTG) [ n = 6], and T. officinale extract-treated group (TETG) [ n = 6]. Rats included in the MTG and TETG were intragastrically administered metformin (100 mg/kg/day) and T. officinale water extract (1500 mg/kg/day), respectively (State Pharmacopoeia Commission 2020).…”