Mulberry Bark Alleviates Effect of STZ Inducing Diabetic Mice through Negatively Regulating FoxO1

Abstract

Dysfunction of insulin secretion and hyperglycaemia were commonly found due to damaged β cells of pancreas. In our previous research, it was found that mulberry branch bark powder (MBBP) was effective in treating diabetes in mice which were induced by STZ and high fat diet. The present study was designed to evaluate the protective effect of MBBP on STZ-induced β cells injury and investigate underlying mechanisms. By preventive administration of branch bark powder, the damage caused by STZ injection was found to be alleviated. In MBBP feed groups, pathological weight loss was inhibited, fasting blood glucose was controlled, the incidence of diabetes decreased, and blood lipid level and antioxidant capacities were restored. The PI3K/AKT/FoxO1 signal pathway was found to be activated by key proteins expression and gene testing. In liver, the increased PI3K and phosphorylated AKT, the phosphorylated, and inactivated FoxO1, which regulates the expression of gluconeogenic gene and explains the effect of relieving insulin resistance of MBBP. Therefore, the MBBP improves the tolerance of pancreas to the toxicity of STZ involving the PI3K/AKT/FoxO1 signalling pathway.

The Synergistic Influence of Polyflavonoids from Citrus aurantifolia on Diabetes Treatment and Their Modulation of the PI3K/AKT/FOXO1 Signaling Pathways: Molecular Docking Analyses and In Vivo Investigations

“…However, the supplementation of hesperidin, diosmin, and the LPE-polyflavonoids remarkably orchestrated the PI3K, p-AKT, FOXO1, and AMPK gene expressions in comparison to those in the diabetic rats. Similar observations were previously demonstrated by Qiu et al [87], who reported that diabetic rats exhibited lower gene expressions of PI3K, p-AKT, and FOXO1 in their pancreatic and liver tissues. It is well known that the mechanism of insulin fundamentally relies on the sequential activations and correlated interactions of the PI3K, p-AKT, and FOXO1 signals to lessen the glucose in blood [88].…”

Network Pharmacology Prediction and Metabolomics Validation of the Novel Targets of Morus alba L. against High-Fat Diet-Induced Diabetes Mellitus in C57/6J Mice

“…Te bark from the mulberry branches was scraped, dried, and crushed into powder. Te powder was weighed and blended with a regular diet to get a 10% MBBP diet for mice, which was optimized according to previous research [9].…”

“…Mice were randomly assigned to 3 groups: the normal control group (normal), the high-fat diet and STZ injection group (model), and the 10% MBBPtreated group (treated). Te dose of 10% MBBP is the effective dose determined in the previous study [9]. Te mice in the normal group were fed a normal laboratory diet.…”

“…Its extracts and active components have many positive biological efects such as inhibition of alphaglucosidase, antioxidant efect, neuroprotective activity, and anticancer properties [6][7][8]. In our previous research, mulberry branch bark powder (MBBP) demonstrated efective hypoglycemic action [9,10], but the mechanisms and targets have not been fully elucidated.…”