A herbal formula containing roots of Salvia miltiorrhiza (Danshen) and Pueraria lobata (Gegen) inhibits inflammatory mediators in LPS-stimulated RAW 264.7 macrophages through inhibition of nuclear factor κb (NFκB) pathway

Abstract

Ethnopharmacological relevance: The herbal formula DG, containing roots of Salvia miltiorrhiza (Danshen) and Pueraria lobata (Gegen), has long history in treating cardiovascular diseases. It has been shown to be able to reduce intima-media thickening in coronary patients in our previous clinical study. Since intima-media thickening is the hallmark of atherosclerotic disease, the etiology of which is inflammation of the arterial wall, the mechanism underlying the effect of DG may be related to its anti-inflammatory activities. Aim of study: The present study aims to determine the anti-inflammatory activity of DG and elucidate its underlying mechanisms with regards to its molecular basis of action. Materials and method: The anti-inflammatory effect of DG was studied by using lipopolysaccharide (LPS)-stimulated activation of nuclear factor κB (NFκB) pathway and subsequent production of inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and macrophage chemotactic protein-1 (MCP-1), in mouse RAW 264.7 macrophages. Results: The present study demonstrated that DG could suppress the production of NO and PGE2 through the inhibition of iNOS and COX-2 genes. DG could also inhibit the production of IL-1β, IL-6 and MCP-1, but not TNF-α, through the inhibition of respective mRNA expressions. Further investigations showed the inhibitory effect of DG on activation of IKKα/β and degradation of IκBα, thus preventing nuclear translocation of NFκB. All these results suggested the inhibitory effects of DG on the production of inflammatory mediators through the inhibition of the NFκB pathway. Conclusions: The inhibitory effects of DG on the production of inflammatory mediators by LPS-stimulated RAW 264.7 macrophages, are accomplished by inhibiting the nuclear translocation of NFκB through inactivating IKKα/β and preventing degradation of IκBα. © 2012 Elsevier Ireland Ltd.