Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway

Abstract

BackgroundInflammation induced by oxidized low-density lipoprotein (ox-LDL) plays an important role in the pathogenesis of atherosclerosis. Recently, roles of autophagy against inflammation in the process of atherosclerosis have drawn increasing attention. Here, we tested the possible molecular mechanisms by which berberine confers an anti-inflammatory effect in macrophages by upregulation of autophagy.MethodsJ774A.1 macrophages were incubated with various doses of ox-LDL for various times. We evaluated the inflammatory factors and autophagy proteins (LC3II/LC3I, and SQSTM1/p62) to ascertain the optimal dose and time. Ox-LDL–induced inflammatory factors and autophagy in J774A.1 cells were tested by the AimPlex multiplex assay, Western blotting, confocal microscopy, and transmission electron microscopy in the presence of berberine or chloroquine (CQ). Adenosine 5’-monophosphate-activated protein kinase (AMPK) inhibitor compound C was used to evaluate the AMPK/mTOR signaling pathway.ResultsBerberine dose- and time-dependently reduced ox-LDL–induced inflammation and increased the ratio of LC3II/LC3I, and SQSTM1/p62 in J774A.1 cells. CQ significantly attenuated the berberine-induced autophagy and anti-inflammation. In addition, berberine increased the ratio of p-AMPK/AMPK and decreased the ratio of p-mTOR/mTOR. AMPK inhibitor compound C abolished berberine-induced autophagy and promoted p-mTOR/mTOR expression in J774A.1 cells.ConclusionBerberine treatment inhibits inflammation in J774A.1 cells by inducing autophagy, which is mediated through activation of the AMPK/mTOR signaling pathway. Importantly, this study provides new insight into berberine’s molecular mechanism and its therapeutic potential in the treatment of atherosclerosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0450-z) contains supplementary material, which is available to authorized users.

Effect of new berberine derivatives on colon cancer cells

“…Although few studies have described the ability of other BBR derivatives to induce autophagy, our data are in agreement with the results obtained with BBR in lung [16], liver [17], and hepatoma [18] cancer cell lines as well as in macrophages [19], adding a piece of information to the field of research aiming at investigating the proautophagic power of BBR [16][17][18][19]. The impact of autophagy on the response of cancer cells to BBR derivatives (and on their cytotoxicity) is still under investigation, in order to define whether this process could ensure cancer cell survival or act as a form of death, given that two opposite roles have been attributed to it [11,12,20,21].…”

Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway

“…Both HSL and ATGL are phosphorylated by AMPK [16]. Studies have found that BBR regulated the metabolism of TG, cholesterol and glucose by regulating the expression of AMPK [17, 18]. In our study, the effects of BBR on p-HSL and ATGL were partially blocked by Compound C, which suggests that AMPK at least partially regulates the effects of BBR on p-HSL and ATGL.…”

Activation of AMPK by chitosan oligosaccharide in intestinal epithelial cells: Mechanism of action and potential applications in intestinal disorders

“…metformin and aspirin) and natural compounds (e.g. resveratrol and berberine) has been shown to ameliorate metabolic syndrome-associated disorders including type II diabetes mellitus, hypertension, dyslipidemia, atherosclerosis and Alzheimer's disease [29][30][31][32][33][34]. Importantly, AMPK activators such as aspirin, metformin and resveratrol have been shown to have potential in extending lifespan of organisms by activating sirtuins, a group of histone/protein deacetylases involved in combating aging [35][36][37].…”