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Abstract Title:

Fisetin inhibits IL-31 production in stimulated human mast cells: Possibilities of fisetin being exploited to treat histamine-independent pruritus.

Abstract Source:

Life Sci. 2018 May 15 ;201:121-129. Epub 2018 Mar 28. PMID: 29604269

Abstract Author(s):

Denis Nchang Che, Byoung Ok Cho, Jae Young Shin, Hyun Ju Kang, Young-Soo Kim, Seon Il Jang

Article Affiliation:

Denis Nchang Che

Abstract:

: Interleukin-31 (IL-31) is a recently discovered cytokine that is tightly linked to the pathogenesis of pruritus seen in atopic dermatitis. Flavonoids, like fisetin, are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions.

AIM: the present study sought to investigate whether fisetin modulates IL-31 and histamine release in human mast cells (HMC-1).

MAIN METHODS: HMC-1 cells were pretreated with fisetin at various doses and stimulated with phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PI) for different time intervals. We evaluated IL-31 production and histamine release and signaling mechanism of the action of fisetin on IL-31 production. We also investigated the effects of fisetin on scratching behaviors in mice.

KEY FINDINGS: Fisetin decreased PI-stimulated mRNA expression and production of IL-31 in HMC-1 cells. Fisetin inhibited PI-induced phosphorylation of mitogen-activated protein kinases that further suppressed nuclear factor (NF-κB) activation and translocation to the nucleus through the inhibition of IκB-α phosphorylation. Fisetin also prevented mast cell release of histamine in HMC-1 cells. Mice in-vivo studies show that fisetin reduced scratching behaviors in mice.

SIGNIFICANCE: These pharmacological actions of fisetin provide new suggestions that fisetin can be of potential use for the treatment of pruritus that cannot be treated with histamine receptor blockers alone.

Study Type : In Vitro Study

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