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柴胡提取物通过 Nrf2 和 TLRs 信号通路对罗非鱼(Oreochromis niloticus)氧化损伤的抗氧化、抗炎和保肝作用。

Anti-oxidative, anti-inflammatory and hepatoprotective effects of Radix Bupleuri extract against oxidative damage in tilapia (Oreochromis niloticus) via Nrf2 and TLRs signaling pathway.

机构信息

Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxim, 214081, China; International Joint Research Laboratory for Fish Immunopharmacology, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China.

Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, 214081, China.

出版信息

Fish Shellfish Immunol. 2019 Oct;93:395-405. doi: 10.1016/j.fsi.2019.07.080. Epub 2019 Jul 30.

Abstract

Radix Bupleuri extract (RBE) is one of the most popular oriental herbal medicines, which has anti-oxidative and anti-inflammatory properties. However, its protective effects and underlying molecular mechanisms on oxidative damage in tilapia are still unclear. The aims of the study were to explore the anti-oxidative, anti-inflammatory and hepatoprotective effects of RBE against oxidative damage, and to elucidate underlying molecular mechanisms in fish. Tilapia received diet containing three doses of RBE (0, 1 and 3 g/kg diet) for 60 days, and then were given an intraperitoneal injection of HO or saline. Before injection, RBE treatments improved growth performance and partial anti-oxidative capacity in tilapia. After oxidative damage, RBE pretreatments were able to signally reduce the higher serum aminotransferases, alkaline phosphatase (AKP) and liver necrosis. In serum and liver, the abnormal lipid peroxidation level and antioxidant status induced by HO injection were restored by RBE treatments. Furthermore, RBE treatments activated erythroid 2-related factor 2 (Nrf2) signaling pathway, which promoted the gene expression of heme oxygenase 1 (HO-1), NAD(P) H:quinone oxidoreductase 1 (NQO-1), glutathione-S-transferase (GST) and catalase (CAT). Meanwhile, RBE treatments reduced inflammatory response by inhibiting TLRs-MyD88-NF-κB signaling pathway, accompanied by the lower interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-8 mRNA levels. In addition, RBE treatments upregulated complement (C3) gene expression and downregulated heat shock protein (HSP70) gene expression. In conclusion, the current study suggested that RBE pretreatments protected against HO-induced oxidative damage in tilapia. The beneficial activity of RBE may be due to the modulation of Nrf2/ARE and TLRs-Myd88-NF-κB signaling pathway.

摘要

柴胡提取物(RBE)是最受欢迎的东方草药之一,具有抗氧化和抗炎特性。然而,其对罗非鱼氧化损伤的保护作用及其潜在的分子机制尚不清楚。本研究旨在探讨 RBE 对罗非鱼氧化损伤的抗氧化、抗炎和保肝作用,并阐明其潜在的分子机制。罗非鱼接受含有三种剂量 RBE(0、1 和 3 g/kg 饮食)的饮食 60 天,然后腹腔注射 HO 或生理盐水。注射前,RBE 处理提高了罗非鱼的生长性能和部分抗氧化能力。氧化损伤后,RBE 预处理能够显著降低血清转氨酶、碱性磷酸酶(AKP)和肝坏死升高。在血清和肝脏中,RBE 处理可恢复 HO 注射引起的异常脂质过氧化水平和抗氧化状态。此外,RBE 处理激活了红细胞 2 相关因子 2(Nrf2)信号通路,促进了血红素加氧酶 1(HO-1)、NAD(P)H:醌氧化还原酶 1(NQO-1)、谷胱甘肽-S-转移酶(GST)和过氧化氢酶(CAT)的基因表达。同时,RBE 处理通过抑制 TLRs-MyD88-NF-κB 信号通路减少炎症反应,伴随白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和 IL-8mRNA 水平降低。此外,RBE 处理上调补体(C3)基因表达,下调热休克蛋白(HSP70)基因表达。综上所述,本研究表明 RBE 预处理可防止 HO 诱导的罗非鱼氧化损伤。RBE 的有益活性可能归因于 Nrf2/ARE 和 TLRs-Myd88-NF-κB 信号通路的调节。

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