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蜜橘素通过上调 Nrf-2 信号通路抑制胶原诱导性关节炎大鼠的氧化应激和炎症。

Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats.

机构信息

Department of Orthopedic Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Pharmacology. 2019;104(3-4):187-195. doi: 10.1159/000501163. Epub 2019 Jul 25.

Abstract

BACKGROUND/AIMS: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats.

METHODS

TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1β [IL-1β], -IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism.

RESULTS

TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1β, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway.

CONCLUSION

TAN might have potential as a therapeutic agent for the treatment of RA.

摘要

背景/目的:橘红(TAN)是一种主要存在于橘子皮中的植物化学物质,也是一种重要的中草药,具有多种生物学特性,尤其是抗氧化和抗炎作用。然而,其作用机制尚不清楚。基于这些发现,本研究旨在评估 TAN 对牛型 II 胶原诱导性关节炎大鼠的抗氧化和抗炎作用。

方法

TAN(50mg/kg)每日口服一次,共 14 天。通过生化测定(关节弹性蛋白酶、髓过氧化物酶、脂质过氧化终产物[MDA]、抗氧化酶,如超氧化物歧化酶、过氧化氢酶、谷胱甘肽)、一氧化氮和炎症细胞因子(白细胞介素-1β[IL-1β]、-IL-10、肿瘤坏死因子-α[TNF-α]、干扰素-γ[IFN-γ]和前列腺素 E2[PGE2])评估治疗效果。TAN 对类风湿关节炎(RA)的保护作用表现为关节炎评分降低。此外,还评估了 Nrf-2 信号通路,以阐明其分子机制。

结果

TAN 通过降低氧化应激损伤和调节炎症细胞因子表达,对 RA 具有治疗作用,包括抑制 MDA 产物的积累,降低 IL-1β、TNF-α、IFN-γ和 PGE2 水平,增强 IL-10 和抗氧化酶活性,从而激活 Nrf-2 信号通路。

结论

TAN 可能具有作为治疗 RA 的治疗剂的潜力。

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