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姜黄素、四氢姜黄素和八氢姜黄素在脂多糖刺激的RAW264.7巨噬细胞中的抗炎和抗氧化活性比较

Comparation of Anti-Inflammatory and Antioxidantactivities of Curcumin, Tetrahydrocurcuminand Octahydrocurcuminin LPS-Stimulated RAW264.7 Macrophages.

作者信息

Xie Qing-Feng, Cheng Juan-Juan, Chen Jin-Fen, Feng Yu-Chao, Lin Guo-Shu, Xu Yang

机构信息

The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China.

出版信息

Evid Based Complement Alternat Med. 2020 Dec 22;2020:8856135. doi: 10.1155/2020/8856135. eCollection 2020.

Abstract

Curcumin (CUR) possesses pronounced anti-inflammatory and antioxidant activities. Generally, the clinical application of CUR is restricted due to its apparent unstability and poor absorption, and the biological activities of CUR may be closely associated with its metabolites. Tetrahydrocurcumin (THC) and octahydrocurcumin (OHC) are two major hydrogenated metabolites of CUR with appreciable biological potentials. Here, we comparatively explored the anti-inflammatory and antioxidant activities of CUR, THC, and OHC in lipopolysaccharide- (LPS-) induced RAW264.7 macrophages. The results revealed that CUR, THC, and OHC dose-dependently inhibited the generation of NO and MCP-1 as well as the gene expression of MCP-1 and iNOS. Additionally, CUR, THC, and OHC significantly inhibited NF-B activation and p38MAPK and ERK phosphorylation, while substantially upregulated the Nrf2 target gene expression (HO-1, NQO-1, GCLC, and GCLM). Nevertheless, zinc protoporphyrin (ZnPP), a typical HO-1 inhibitor, significantly reversed the alleviative effect of CUR, THC, and OHC on LPS-stimulated ROS generation. These results demonstrated that CUR, THC, and OHC exerted beneficial effect on LPS-stimulated inflammatory and oxidative responses, at least partially, through inhibiting the NF-B and MAPKs pathways and activating Nrf2-regulated antioxidant gene expression. Particularly, THC and OHC might exert superior antioxidant and anti-inflammatory activities to CUR in LPS-stimulated RAW264.7 cells, which can be further explored to be a promising novel effective agent for inflammatory treatment.

摘要

姜黄素(CUR)具有显著的抗炎和抗氧化活性。一般来说,CUR的临床应用因其明显的不稳定性和低吸收率而受到限制,并且CUR的生物活性可能与其代谢产物密切相关。四氢姜黄素(THC)和八氢姜黄素(OHC)是CUR的两种主要氢化代谢产物,具有可观的生物潜力。在此,我们比较研究了CUR、THC和OHC在脂多糖(LPS)诱导的RAW264.7巨噬细胞中的抗炎和抗氧化活性。结果显示,CUR、THC和OHC呈剂量依赖性地抑制NO和MCP-1的生成以及MCP-1和iNOS的基因表达。此外,CUR、THC和OHC显著抑制NF-κB激活以及p38MAPK和ERK磷酸化,同时大幅上调Nrf2靶基因表达(HO-1、NQO-1、GCLC和GCLM)。然而,典型的HO-1抑制剂锌原卟啉(ZnPP)显著逆转了CUR、THC和OHC对LPS刺激的ROS生成的缓解作用。这些结果表明,CUR、THC和OHC至少部分地通过抑制NF-κB和MAPKs通路以及激活Nrf2调节的抗氧化基因表达,对LPS刺激的炎症和氧化反应发挥有益作用。特别是,在LPS刺激的RAW264.7细胞中,THC和OHC可能比CUR具有更强的抗氧化和抗炎活性,这可进一步探索作为一种有前景的新型炎症治疗有效药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3efb/7772021/9d0f5324efb6/ECAM2020-8856135.001.jpg

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