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降香黄檀 9-羟基-6,7-二甲氧基二氢卡瓦胡椒醇通过血红素加氧酶-1 抑制脂多糖刺激的小鼠 BV2 小胶质细胞中 NF-κB 相关神经炎症反应

Inhibitory effect of 9-hydroxy-6,7-dimethoxydalbergiquinol from Dalbergia odorifera on the NF-κB-related neuroinflammatory response in lipopolysaccharide-stimulated mouse BV2 microglial cells is mediated by heme oxygenase-1.

机构信息

Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Republic of Korea.

出版信息

Int Immunopharmacol. 2013 Nov;17(3):828-35. doi: 10.1016/j.intimp.2013.08.024. Epub 2013 Sep 19.

DOI:10.1016/j.intimp.2013.08.024
PMID:24055019
Abstract

The heartwood of Dalbergia odorifera T. Chen (Leguminosae) is an important source of traditional Korean and Chinese medicines. 9-Hydroxy-6,7-dimethoxydalbergiquinol (HDDQ), a compound isolated from D. odorifera, has various biological activities. The aim of this study was to determine the efficacy of HDDQ in modulating the regulation of anti-inflammatory activity through the upregulation of heme oxygenase (HO)-1 in BV2 microglia. HDDQ inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), and the production of cyclooxygenase (COX)-2 and COX-2-derived prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated mouse BV2 microglia. HDDQ also reduced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production, and suppressed the phosphorylation and degradation of IκB-α and the nuclear translocation of p65 in mouse BV2 microglia in response to LPS. Furthermore, HDDQ upregulated HO-1 expression via nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in mouse BV2 microglia. Using tin protoporphyrin (SnPP), an HO activity inhibitor, we verified that the inhibitory effects of HDDQ on the proinflammatory mediators NO, PGE2, TNF-α, and IL-1β, and nuclear factor kappa B (NF-κB) DNA-binding activity are associated with the induction of HO-1 expression. Our data suggest that HDDQ has therapeutic potential against neurodegenerative diseases caused by neuroinflammation.

摘要

降香油(Dalbergia odorifera T. Chen,豆科)的心材是传统韩国和中药的重要来源。从降香油中分离得到的 9-羟基-6,7-二甲氧基二氢巴马汀(HDDQ)具有多种生物活性。本研究旨在确定 HDDQ 通过上调 BV2 小胶质细胞中血红素加氧酶(HO)-1 的表达来调节抗炎活性的功效。HDDQ 抑制诱导型一氧化氮合酶(iNOS)、iNOS 衍生的一氧化氮(NO)、环氧化酶(COX)-2 和 COX-2 衍生的前列腺素 E2(PGE2)的蛋白表达,在脂多糖(LPS)刺激的小鼠 BV2 小胶质细胞中。HDDQ 还减少肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的产生,并抑制 LPS 刺激的小鼠 BV2 小胶质细胞中 IκB-α的磷酸化和降解以及 p65 的核易位。此外,HDDQ 通过核因子 E2 相关因子 2(Nrf2)的核易位上调 HO-1 的表达。用血红素加氧酶(HO)活性抑制剂锡原卟啉(SnPP),我们验证了 HDDQ 对促炎介质 NO、PGE2、TNF-α 和 IL-1β以及核因子κB(NF-κB)DNA 结合活性的抑制作用与 HO-1 表达的诱导有关。我们的数据表明,HDDQ 具有针对神经炎症引起的神经退行性疾病的治疗潜力。

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