Berberine chloride ameliorated PI3K/Akt‐p/SIRT‐1/PTEN signaling pathway in insulin resistance syndrome induced in rats

Abstract

The liver is the main organ involved in lipid metabolism process and it helps in drug detoxification. Insulin resistance is considered one of risk reasons which lead to several metabolic diseases. Currently, berberine (BER) occupies a huge challenge against multiple diseases with no toxic effect. The present work was aimed to identify, does BER-chloride has a poisonous influence on the liver? and investigating the outcome of BER-chloride on PI3K/Akt-p/SIRT-1/PTEN pathway during insulin resistance syndrome. The insulin resistance model was achieved in experimental female rats via high-fat diet (HFD). Glucose, insulin, lipid profiles, and hepatic oxidative stress parameters were assessed. PI3K, AKt-p, SIRT-1, and PTEN levels in hepatic tissue were determined at genome and protein levels. Further adiponectin concentration was performed in serum, hepatic, and white adipose tissues. Molecular study of fold alteration in insulin, insulin receptor, and retinol binding protein-4 (RBP4) in liver was done. Practical applicationsObesity syndrome causes multiple obstacles in modern years. The current results revealed elevation the body weight of rats, plasma glucose, homeostatic model assessment, glycated hemoglobin, insulin, and lipid profiles concentrations in a group of rats, which nourished HFD for 8 weeks and this rise, was diminished after 2 weeks from BER-chloride administration. Further, BER-chloride improved transaminases enzymes, pro-oxidant, and antioxidant defense system, PI3K, AKt-p, SIRT-1, and PTEN in the liver, with downregulation of hepatic RBP4. Hence, these data provide a crucial message that BER-chloride enhanced both hepatic function and insulin signaling pathways that might be of therapeutic importance to insulin resistance with no harmful effect on the liver. BER-chloride is predicted to be a drug of choice for obesity complications cure. K E Y W O R D Sberberine chloride, hepatotoxicity, insulin receptor, liver

Berberine Slows the Progression of Prediabetes to Diabetes in Zucker Diabetic Fatty Rats by Enhancing Intestinal Secretion of Glucagon-Like Peptide-2 and Improving the Gut Microbiota

“…Previous studies reported improvements in fatty liver (42)(43)(44)48) and diabetic nephropathy (45-47) with berberine treatment. It is true that berberine can be toxic to the liver and kidneys (64), but the present study used a berberine dosage known to be therapeutic in rats (25,28,29,31,32,48,52,53). Nevertheless, the liver and kidney changes will be examined in future studies.…”

“…In this study, berberine was administered at a dose of 100 mg/kg/d for 3 weeks, based on previous studies in rats (28,31,32,47). The antidiabetic effect of berberine is dose-dependent.…”

“…Berberine possesses a low oral bioavailability, however, it has exhibited the metabolites of berberine showed similar bioactivities and the concentrations of its major metabolites were at relatively high levels (63). Furthermore, in regard to the treatment duration, previous studies have shown that it would take two weeks to get the significant effect of improving insulin resistance (28,31,47), and other previous studies showed more treatment duration of five to eight weeks (25,29,32,46,48,52,53). In present study, it has been shown that 3 weeks was sufficient to reach a plateau in the effects of berberine, at least in rats, but it would have to be verified in humans.…”

“…Berberine, an isoquinoline alkaloid originally isolated from the Chinese herb Coptis chinensis, has been used to treat diarrhea for many years in China (23,24). Recently, researchers have found that berberine improves insulin resistance and endotoxemia in rat models of diabetes and patients with T2DM (25)(26)(27)(28), and these actions may be related to the effects of berberine on the gut microbiota or gut mucosal integrity (29,30). In our previous study, we found that berberine protects the intestinal barrier and mucosal integrity and helps to maintain GLP-2 secretion by intestinal L cells (31).…”

Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review

“…Berberine inhibits the release of MMP-2 from tumor cells and thus inhibits tumor cell destruction of the tissue matrix. Berberine increased the activities of numerous proteins involved in proliferation, such as Janus Kinase 2 (JAK2), Phosphoinositide 3-kinase (PI3K), activator protein-1 (AP-1), and NF-kappaB (Mahata et al, 2011;Fu et al, 2013;Wu et al, 2013;Belanova et al, 2019;El-Zeftawy et al, 2019;Jiang et al, 2019). These proteins decreased IL-8 expression in the TNBC cell line, MDA-MB-231.…”