AKT-targeted anti-inflammatory activity of the methanol extract of Chrysanthemum indicum var. albescens

Abstract

Ethnopharmacological relevance: Wild chrysanthemum (Chrysanthemum indicum) is one of well-known medicinal plants traditionally used in Korea and China. As a variant of wild chrysanthemum, white wild chrysanthemum (Chrysanthemum indicum var. albescens) is also ethnopharmacologically applied to treat various symptoms such as inflammatory diseases.

Aim of study: Although the anti-inflammatory activity of Chrysanthemum indicum has been reported, the anti-inflammatory activity and underlying molecular mechanism of white wild chrysanthemum are poorly understood.

Materials and methods: The effects of Chrysanthemum indicum var. albescens methanol extract (Civ-ME) on the production of inflammatory mediators, expression of pro-inflammatory genes, cell viability, and the activities of intracellular signaling molecules and transcription factors were investigated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Results: Civ-ME suppressed the production of both nitric oxide (NO) and prostaglandin E₂ (PGE₂) without cytotoxicity in LPS-stimulated RAW264.7 cells. Civ-ME was found to reduce the mRNA levels of inflammatory genes such as inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α and reduced NF-κB-mediated transcriptional activation. Civ-ME inhibited the nuclear translocation of NF-κB (p65 and p50), and its upstream signaling composed of IκBα and IKKα/β. An NF-κB luciferase reporter gene assay and an in vitro kinase assay confirmed that AKT1 and AKT2 might be direct pharmacological targets of Civ-ME. In addition, luteolin was identified by HPLC analysis as the main active pharmacological components of Civ-ME.

Conclusion: Civ-ME exerts an anti-inflammatory effect by targeting AKT1 and AKT2 in the NF-κB signaling pathway in macrophage-mediated inflammatory responses.

Keywords: AKT; Anti-inflammatory activity; Chrysanthemum indicum var. albescens; Macrophage; NF-κB.