咖啡酸辛酯通过核因子红细胞相关因子 2/血红素氧合酶-1 途径改善 D-半乳糖胺/脂多糖诱导的大鼠暴发性肝炎。

Sinapic acid ameliorates D-galactosamine/lipopolysaccharide-induced fulminant hepatitis in rats: Role of nuclear factor erythroid-related factor 2/heme oxygenase-1 pathways.

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

出版信息

World J Gastroenterol. 2021 Feb 21;27(7):592-608. doi: 10.3748/wjg.v27.i7.592.

BACKGROUND

Sinapic acid (SA) has been shown to have various pharmacological properties such as antioxidant, antifibrotic, anti-inflammatory, and anticancer activities. Its mechanism of action is dependent upon its ability to curb free radical production and protect against oxidative stress-induced tissue injuries.

AIM

To study the hepatoprotective effects of SA against lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver failure (ALF) in rats.

METHODS

Experimental ALF was induced with an intraperitoneal (i.p.) administration of 8 μg LPS and 800 mg/kg D-GalN in normal saline. SA was administered orally once daily starting 7 d before LPS/D-GalN treatment.

RESULTS

Data showed that SA ameliorates acute liver dysfunction, decreases serum levels of alanine transaminase (ALT), and aspartate aminotransferase (AST), as well as malondialdehyde (MDA) and NO levels in ALF model rats. However, pretreatment with SA (20 mg/kg and 40 mg/kg) reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and levels of inflammatory cytokines (tumor necrosis factor-α and interleukin 6). Also, SA increased the activity of the nuclear factor erythroid-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway.

CONCLUSION

In conclusion, SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-κB.

背景

芥子酸（SA）已被证明具有多种药理作用，如抗氧化、抗纤维化、抗炎和抗癌活性。其作用机制依赖于其抑制自由基产生和防止氧化应激诱导的组织损伤的能力。

目的

研究芥子酸（SA）对脂多糖（LPS）/D-半乳糖胺（D-GalN）诱导的大鼠急性肝衰竭（ALF）的保护作用。

方法

采用腹腔内（i.p.）注射 8 μg LPS 和 800 mg/kg D-GalN 在生理盐水诱导实验性 ALF。SA 于 LPS/D-GalN 处理前 7 天开始每日口服给药。

结果

数据显示，SA 改善急性肝功能障碍，降低 ALF 模型大鼠血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）以及丙二醛（MDA）和一氧化氮（NO）水平。然而，SA（20mg/kg 和 40mg/kg）预处理可降低核因子 kappa-轻链增强子的活化 B 细胞（NF-κB）的激活和炎症细胞因子（肿瘤坏死因子-α和白细胞介素 6）的水平。此外，SA 增加了核因子红细胞相关因子 2/血红素加氧酶-1（Nrf2/HO-1）信号通路的活性。