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陈年红蒜提取物通过诱导血红素加氧酶-1 降低脂多糖诱导的 RAW264.7 巨噬细胞一氧化氮的产生和急性肺炎症。

Aged red garlic extract reduces lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages and acute pulmonary inflammation through haeme oxygenase-1 induction.

机构信息

Department of Physiology, Gyeongsang National University School of Medicine, Jinju, South Korea.

出版信息

Acta Physiol (Oxf). 2012 May;205(1):61-70. doi: 10.1111/j.1748-1716.2012.02425.x. Epub 2012 Mar 9.

Abstract

AIM

It is known that garlic has antioxidative and anti-inflammatory properties. Aged red garlic (ARG), a novel aged garlic formulation, has higher antioxidant effects than fresh raw garlic. This study was performed to examine the anti-inflammatory effects of ARG extract (ARGE).

METHODS

The anti-inflammatory effects of ARGE were evaluated in the lipopolysaccharide (LPS)-treated Raw 264.7 macrophages and acute lung inflammatory mice. NO production was determined by the Griess method, and iNOS, HO-1 and COX-2 expressions were measured using Western blot analysis. Histology and inflammation extent of lung were analysed using haematoxylin-eosin staining and immunohistochemistry.

RESULTS

ARGE treatment markedly reduced LPS-induced nitrite production in RAW 264.7 macrophages and reduced inducible nitric oxide synthase (iNOS) expression. Treatment of cells with ARGE led to a significant increase in haeme oxygenase-1 (HO-1) protein expression, which was mediated by stimulating the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Treatment with zinc protoporphyrin, a selective inhibitor of HO-1, significantly reversed the ARGE-mediated inhibition of nitrite production (P < 0.05). In LPS-induced inflammatory mice, ARGE treatment down-regulated iNOS and COX-2 expressions, while it up-regulated HO-1 expression.

CONCLUSION

These results show that ARGE reduces LPS-induced nitric oxide production in RAW 264.7 macrophages through HO-1 induction and suggest that ARGE may have potential effects on prevention and treatment of acute inflammatory lung injury.

摘要

目的

已知大蒜具有抗氧化和抗炎特性。陈年红蒜(ARG)是一种新型的陈年大蒜制剂,其抗氧化效果高于新鲜生蒜。本研究旨在研究 ARG 提取物(ARGE)的抗炎作用。

方法

在脂多糖(LPS)处理的 Raw 264.7 巨噬细胞和急性肺炎症小鼠中评估 ARGE 的抗炎作用。通过格里斯法测定 NO 产生,通过 Western blot 分析测定诱导型一氧化氮合酶(iNOS)、HO-1 和 COX-2 的表达。用苏木精-伊红染色和免疫组织化学分析肺组织学和炎症程度。

结果

ARGE 处理显著降低了 LPS 诱导的 Raw 264.7 巨噬细胞中亚硝酸盐的产生,并降低了诱导型一氧化氮合酶(iNOS)的表达。ARGE 处理导致血红素加氧酶-1(HO-1)蛋白表达显著增加,这是通过刺激核因子红细胞 2 相关因子 2(Nrf2)的表达介导的。用血红素加氧酶-1 的选择性抑制剂锌原卟啉处理可显著逆转 ARGE 介导的亚硝酸盐产生抑制(P <0.05)。在 LPS 诱导的炎症小鼠中,ARGE 处理下调了 iNOS 和 COX-2 的表达,而上调了 HO-1 的表达。

结论

这些结果表明,ARGE 通过 HO-1 诱导降低了 LPS 诱导的 RAW 264.7 巨噬细胞中一氧化氮的产生,并表明 ARGE 可能对预防和治疗急性炎症性肺损伤具有潜在作用。

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