Qingre Huoxue Decoction regulates macrophage polarisation to attenuate atherosclerosis through the inhibition of NF-κB signalling-mediated inflammation

摘要

Ethnopharmacological relevance: Atherosclerosis (AS) is a common pathogenesis of cardiovascular diseases. Qingre Huoxue Decoction (QRHX) is an herbal formula used for the prevention and treatment of AS. However, the potential mechanism of QRHX is not clear. @@@ Aim of the study: In our study, RNA sequencing combined with preclinical models were used to analyse the effect and mechanism of QRHX for the treatment of AS. @@@ Materials and methods: For in vivo studies, ApoE(-/-) mice were fed with a high-fat diet to induce AS. We measured weight, blood lipid, inflammatory cytokines, lipid deposition, plaque, and the M1/M2 macrophage. For in vitro studies, RAW264.7 were induced by lipopolysaccharides and treated with different concentrations of QRHX. We focusd on the relationship between QRHX, the NF-kappa B pathway, and macrophage polarisation, and performed simultaneous RNA sequencing both in vivo and in vitro. @@@ Results: In vivo, QRHX decreased weight, improved blood lipid, relieved the degree of lipid deposition, reduced plaque area, decreased the levels of inflammatory cytokines (MCP-1, NLRP3, and TNF alpha), down-regulated the expression of iNOS, and up-regulated the expression of Arg-1. In vitro, QRHX down-regulated M1 markers, iNOS and CCR7, with lower concentrations of IL-1 beta; furthermore, QRHX up-regulated M2 markers, Arg-1, CD163, Ym-1, and Fizz-1, with higher concentrations of IL-4 and IL-10. RNA sequencing of both samples in vivo and in vitro suggested that NF-kappa B was the target pathway of QRHX to regulate macrophage polarisation; this result was validated at the gene and protein levels. @@@ Conclusions: QRHX induced M2 polarisation, reduced an inflammatory response, and played a role in stabilising plaque by mediating the NF-kappa B signalling pathway.

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