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Int Immunopharmacol. 2017 Nov;52:93-100. doi: 10.1016/j.intimp.2017.08.032. Epub 2017 Sep 8.

Berberine suppresses LPS-induced inflammation through modulating Sirt1/NF-κB signaling pathway in RAW264.7 cells.

Author information

1
Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Rd., Nanjing 210023, China.
2
Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Rd., Nanjing 210023, China; Department of Endocrinology, The Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Rd., Nanjing 210029, China.
3
Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Rd., Nanjing 210023, China; Department of Endocrinology, The Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Rd., Nanjing 210029, China. Electronic address: wbshang@njucm.edu.cn.

Abstract

Chronic inflammation is a major contributing factor in the pathogenesis of many diseases. Natural product berberine (BBR) exhibits potent anti-inflammatory effect in vitro and in vivo, while the underlying mechanisms remain elusive. Sirt1, a NAD+-dependent protein deacetylase, was recently found to play an important role in modulating the development and progression of inflammation. Thus, we speculate that Sirt1 might mediate the inhibitory effect of BBR on inflammation. In LPS-stimulated RAW264.7 macrophages, BBR treatment significantly downregulated the expression of proinflammatory cytokines such as MCP-1, IL-6 and TNF-α. Importantly, BBR potently reversed LPS-induced down-regulation of Sirt1. Consistently, the inhibitory effects of BBR on proinflammatory cytokines expression was largely abrogated by Sirt1 inhibition either by EX527, a Sirt1 inhibitor or Sirt1 siRNA. Further mechanistic studies revealed that BBR-induced inhibition of NF-κB is Sirt1-dependent, as either pharmacologically or genetically inactivating Sirt1 enhanced the IκΒα degradation, IKK phosphorylation, NF-κB p65 acetylation and DNA-binding activity. Taken together, our results provide the first evidence that BBR potently suppressed inflammatory responses in macrophages through inhibition of NF-κB signaling via Sirt1-dependent mechanisms.

KEYWORDS:

Berberine; Inflammation; Macrophage; NF-κB; Sirt1

PMID:
28888780
DOI:
10.1016/j.intimp.2017.08.032
[Indexed for MEDLINE]

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