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

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. Sirti, 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 Sirtl 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-alpha. Importantly, BBR potently reversed LPS-induced down-regulation of Sirtl. Consistently, the inhibitory effects of BBR on proinflammatory cytokines expression was largely abrogated by Sirti inhibition either by EX527, a Sirtl inhibitor or Sirtl siRNA. Further mechanistic studies revealed that BBR-induced inhibition of NF-kappa B is Sirt1-dependent, as either pharmacologically or genetically inactivating Sirtl enhanced the I kappa B alpha degradation, IKK phosphorylation, NF-kappa B 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-kappa B signaling via Sirt1-dependent mechanisms.