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通过抑制小鼠中NF-κB p65依赖性炎症反应来改善刺激性接触性皮炎。

ameliorates irritant contact dermatitis by suppressing NF‑κB p65‑dependent inflammatory responses in mice.

作者信息

Kim Yu-Bin, Kang Eun-Jung, Noh Jung-Ran, An Jin-Pyo, Park Jong-Tae, Oh Won Keun, Kim Yong-Hoon, Lee Chul-Ho

机构信息

Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.

Department of Food Science and Technology, Chungnam National University, Daejeon 34134, Republic of Korea.

出版信息

Exp Ther Med. 2023 Aug 2;26(3):446. doi: 10.3892/etm.2023.12145. eCollection 2023 Sep.

Abstract

As a type of contact dermatitis (CD), irritant CD (ICD) is an acute skin inflammation caused by external irritants, such as soap, water and chemicals. (HJ) is a herbal medicine widely distributed in Asian countries and has anti-inflammatory, antimicrobial and antioxidant effects. The current study aimed to investigate the anti-dermatitis effect of HJ on ICD and determine the molecular basis of this effect using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis mice models and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Mice were orally administered HJ and luteolin, the major compound in HJ, and topically administered TPA on the right ear to induce dermatitis. Topical application of TPA induced ear redness, oedema and increased infiltration of neutrophils and macrophages, which ameliorated following HJ and luteolin administration. The gene expression levels of inflammatory cell migrating chemokines, chemokine ligand 3 (CCL3) and chemokine (C-X-C motif) ligand 2 (CXCL2), and pro-inflammatory cytokine, IL-1β, were reduced in the ears of HJ- and luteolin-treated mice. HJ and luteolin also inhibited the gene expression of chemokines, CCL3 and CXCL2, and pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α, in LPS-stimulated RAW264.7 cells. Moreover, HJ and luteolin decreased the expression levels of two key inflammatory enzymes, cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS), and total and active phosphorylation of NF-κB p65. These results suggest that HJ could have a protective effect against ICD by suppressing inflammatory responses; therefore, HJ is a promising therapeutic strategy for ICD treatment.

摘要

作为接触性皮炎(CD)的一种类型,刺激性接触性皮炎(ICD)是由外部刺激物如肥皂、水和化学物质引起的急性皮肤炎症。(HJ)是一种广泛分布于亚洲国家的草药,具有抗炎、抗菌和抗氧化作用。本研究旨在利用12-氧-十四烷酰佛波醇-13-乙酸酯(TPA)诱导的皮炎小鼠模型和脂多糖(LPS)刺激的RAW264.7细胞,研究HJ对ICD的抗皮炎作用并确定其作用的分子基础。给小鼠口服HJ及其主要成分木犀草素,并在右耳局部涂抹TPA以诱导皮炎。局部涂抹TPA可引起耳发红、水肿以及中性粒细胞和巨噬细胞浸润增加,而给予HJ和木犀草素后这些症状有所改善。在经HJ和木犀草素处理的小鼠耳部,炎症细胞迁移趋化因子、趋化因子配体3(CCL3)和趋化因子(C-X-C基序)配体2(CXCL2)以及促炎细胞因子IL-1β的基因表达水平降低。HJ和木犀草素还抑制了LPS刺激的RAW264.7细胞中趋化因子CCL3和CXCL2以及促炎细胞因子IL-1β、IL-6和TNF-α的基因表达。此外,HJ和木犀草素降低了两种关键炎症酶环氧合酶-2(COX2)和诱导型一氧化氮合酶(iNOS)的表达水平以及NF-κB p65的总磷酸化和活性磷酸化水平。这些结果表明,HJ可能通过抑制炎症反应对ICD具有保护作用;因此,HJ是一种有前景的ICD治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/556d/10443058/e1048a552d78/etm-26-03-12145-g00.jpg

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