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γ-谷维素通过调节 MAPK/Nrf2 信号通路保护人肝细胞(L02)免受过氧化氢诱导的氧化损伤。

Gamma-oryzanol protects human liver cell (L02) from hydrogen peroxide-induced oxidative damage through regulation of the MAPK/Nrf2 signaling pathways.

机构信息

Hunan Engineering Research Center of Livestock and Poultry Health Care, Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha, China.

Changsha University of Science & Technology, Changsha, China.

出版信息

J Food Biochem. 2022 Jul;46(7):e14118. doi: 10.1111/jfbc.14118. Epub 2022 Feb 25.

Abstract

Gamma-oryzanol (Orz), a mixture of the ferulic acid ester of triterpene alcohols and phytosterols, was found abundantly in rice bran and rice bran oil which could be available and served as an antioxidant. The present study was to explore the potential protective effects of Orz on oxidative stress and cell apoptosis in human hepatic cells (L02 cells) induced by hydrogen peroxide (H O ). Flow cytometry detection and Hoechst 33258 staining showed that Orz significantly restored cell cycle and ameliorated apoptosis in H O -challenged L02 cells. Orz pretreatment inhibited H O -induced cell apoptosis by increasing the scavenging of hydroxyl radicals (OH·), and efficiently decreasing the production of nitric oxide (NO). Moreover, a loss of total antioxidant capacity (T-AOC) and adenosine triphosphatase (ATPase) were enhanced in H O -mediated L02 cells pretreated with Orz. Furthermore, preincubation with Orz reduced H O -mediated the proapoptotic protein of Bak expression and the phosphorylation of ASK1, p38, JNK, and ERK, and increased the anti-apoptotic protein of Bcl-xl expression and anti-oxidative stress proteins of Nrf2 and HO-1 expression. The findings suggested that Orz exerts the cytoprotective effects in H O -induced L02 cells apoptosis by ameliorating oxidative stress via inhibiting MAPK signaling pathway and activating Nrf2 signaling pathway. PRACTICAL APPLICATIONS: Gamma-oryzanol (Orz), a mixture of the ferulic acid ester of triterpene alcohols and phytosterols, was found abundantly in rice bran and rice bran oil which could be availably served as an antioxidant. In this study, it was found that Orz exerts the cytoprotective effects in H O -induced L02 cell apoptosis by ameliorating oxidative stress via the inhibition of MAPK signaling pathway and the activation of Nrf2 signaling pathway, which provides a theoretical basis for dietary adding natural products to prevent or treat oxidative stress-related diseases.

摘要

γ-谷维素(Orz)是一种三萜醇和植物甾醇的脂肪酸酯混合物,大量存在于米糠和米糠油中,可用作抗氧化剂。本研究旨在探讨 Orz 对过氧化氢(H2O2)诱导的人肝细胞(L02 细胞)氧化应激和细胞凋亡的潜在保护作用。流式细胞术检测和 Hoechst 33258 染色显示,Orz 可显著恢复 H2O2 诱导的 L02 细胞周期,并改善细胞凋亡。Orz 预处理通过增加羟自由基(OH·)的清除,有效减少一氧化氮(NO)的产生,抑制 H2O2 诱导的细胞凋亡。此外,在 Orz 预处理的 H2O2 介导的 L02 细胞中,总抗氧化能力(T-AOC)和三磷酸腺苷酶(ATPase)的损失增加。此外,Orz 预处理可降低 H2O2 介导的促凋亡蛋白 Bak 表达和 ASK1、p38、JNK 和 ERK 的磷酸化,并增加抗凋亡蛋白 Bcl-xl 表达和抗氧化应激蛋白 Nrf2 和 HO-1 表达。研究结果表明,Orz 通过抑制 MAPK 信号通路和激活 Nrf2 信号通路,改善氧化应激,发挥对 H2O2 诱导的 L02 细胞凋亡的细胞保护作用。实际应用:γ-谷维素(Orz)是一种三萜醇和植物甾醇的脂肪酸酯混合物,大量存在于米糠和米糠油中,可用作抗氧化剂。本研究发现,Orz 通过抑制 MAPK 信号通路和激活 Nrf2 信号通路,改善氧化应激,发挥对 H2O2 诱导的 L02 细胞凋亡的细胞保护作用,为添加天然产物预防或治疗氧化应激相关疾病提供了理论依据。

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