Modulation of Inflammatory Mediator Production and Signaling Pathways in Macrophages by a Traditional Polyherbal Mixture

초록

Chronic inflammation contributes to numerous diseases, pointing to the need for safer and more effective anti-inflammatory agents, particularly those derived from natural sources. A traditional polyherbal mixture (PHM), composed of 13 medicinal plants and historically used for respiratory ailments, was evaluated for its anti-inflammatory potential. Lipopolysaccharide (LPS)- stimulated RAW264.7 murine macrophages were used as an established in vitro model of inflammation. Distilled water extract (DE) and 70% ethanol extract (EE) of PHM were prepared and applied to cells concurrently with LPS stimulation. Cytotoxicity and cell response, nitric oxide (NO) production, proinflammatory cytokine secretion, and corresponding gene expression levels were measured, and the activation status of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways was assessed via Western blot analysis of key phosphorylated proteins. Both PHM DE and EE exhibited low cytotoxicity at concentrations effective for anti-inflammatory activity. The extracts significantly inhibited LPS-induced NO production and cytokine secretion in a dose-dependent manner, consistent with the suppressed mRNA expression of Nos2 and these cytokines. Notably, DE generally demonstrated more potent anti-inflammatory activity than EE. Mechanistically, PHM treatment suppressed the LPS-induced activation of key signaling components within the NF-κB and MAPK pathways. The PHM demonstrates significant in vitro anti-inflammatory activity in LPS-stimulated macrophages, mediated in part through the suppression of these signaling pathways. These findings provide a scientific basis for the traditional use of PHM and suggest its potential as a therapeutic candidate for managing inflammatory conditions.

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