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

Xiaodi Fan, Jun Wang, Jincai Hou, Chengren Lin, Alan Bensoussan, Dennis Chang, Jianxun Liu, Bing Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Inflammation 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. Methods: J774A.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. Results: Berberine 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. Conclusion: Berberine 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.

Original languageEnglish (US)
Article number92
JournalJournal of translational medicine
Volume13
Issue number1
DOIs
StatePublished - Mar 15 2015

Keywords

  • AMPK/mTOR
  • Autophagy
  • Berberine
  • Inflammation
  • Macrophage

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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