Anti-inflammatory activity of berberine in non-alcoholic fatty liver disease via the Angptl2 pathway

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. Recent studies have shown that the Angptl2 pathway mediated hepatic inflammatory response plays an important role in the progression of nonalcoholic fatty liver disease. Our study investigated the possible molecular mechanisms of berberine (BBR) in the treatment of the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD via the Angptl2 pathway. Results: At the end of 12 weeks, compared with the control group rats, the high-fat-diet group rats showed obvious pathological and biochemical changes. The levels of pro-infalmmatory cytokines (CCL2, TNF-α) were increased, the infiltration of inflammatory cells (CCR2) was elevated, and the hepatic mRNA and protein levels of Angptl2, NF-κB and Foxo1 were increased to different degrees. Nevertheless, following treatment with BBR, liver tissue pathology, biochemical data, and Angptl2 pathway-related genes expression were significantly ameliorated. Conclusions: Our findings demonstrate that BBR might attenuate the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD through the regulation of the Angptl2 pathway.

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

“…In the present study, the incidence of T2DM was significantly lower in the berberine group than in the IGT group, and 40% of rats in the berberine group reverted to having an NGT. Moreover, treatment with berberine led to significant improvements in blood glucose level, blood lipid levels, and insulin resistance, as supported by the literature (42)(43)(44)(45)(46)(47)(48). To our knowledge, this is the first study to demonstrate that berberine can prevent the progression of prediabetes to T2DM in rats.…”

“…Our previous study found that berberine decreased blood glucose level and insulin resistance in rats with T2DM induced by a highfat diet (31). Previous studies also reported that berberine could improve the blood markers and pathophysiological changes of diabetes in patients and animal models (42)(43)(44)(45)(46)(47)(48). In the present study, the incidence of T2DM was significantly lower in the berberine group than in the IGT group, and 40% of rats in the berberine group reverted to having an NGT.…”

“…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.…”

“…Some studies have showed that the berberine at a low dose of 50mg or 60mg/kg had no significant antidiabetic effect (46,52). Other studies have reported that berberine at a higher dose of 120mg to 300mg had beneficial effects on glucose metabolism with few side effects (25,29,46,48,52,53).Future studies should examine the effect of various doses of berberine on GLP levels in relation to T2DM. Additionally, according to available equations, the dose of 100 mg/kg/day would correspond to a dose of 13.8 mg/kg/day in humans (60 kg) (60).…”

“…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.…”