以往的研究显示，23醋酸石珊瑚甙B（23ABA）具有强效的保肝作用，然而，它在四氯化碳（CCl4）诱导的肝纤维化中的作用和潜在机制仍待确定。本研究旨在调查23ABA对CCl4诱导的肝纤维化的影响，并试图通过调节法尼酰二烯氧化酶X受体（FXR）来阐明潜在机制。体内研究发现，23ABA缓解了CCl4诱导的肝损伤，并且对小鼠没有明显的全身毒性。23ABA抑制了胶原蛋白的产生，降低了小鼠肝脏中透明质酸（HA）和过胶原III前身（PC-III）的血清水平，降低了α-平滑肌肌动蛋白（α-SMA）、纤连蛋白、胶原I和胶原III的mRNA表达。23ABA抑制了转化生长因子-β（TGF-β）和线粒体转录因子A（mtTFA）在肝纤维化小鼠中的mRNA表达和血清水平，降低了白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的表达，以及降低了促炎酶2（COX-2）在纤维化肝中的表达。此外，23ABA降低了肝纤维化小鼠肝脏的活性氧（ROS）和丙二醛（MDA）水平，提高了谷胱甘肽（GSH）水平，并增强了超氧化物歧化酶（SOD）和谷胱甘肽还原酶（GR）的活性，同时增加了核因子-E2相关因子2（Nrf2）的mRNA表达，谷氨酸-半胱氨酸配体酰化酶催化亚基（GCLC）和谷氨酸-半胱氨酸配体酰化酶修饰亚基（GCLM）的mRNA表达。进一步的研究表明，在体内，FXR拮抗剂古谷甾酮（GS）消除了23ABA的抗肝损伤和抗纤维化作用。此外，在CCl4诱导的纤维化小鼠肝中，23ABA对肝炎炎症和氧化应激的抑制作用也被GS处理削弱。总之，23ABA通过FXR介导的调节肝炎炎症和氧化应激，对CCl4诱导的肝损伤和纤维化具有保护作用。版权所有©2023 Elsevier B.V. 保留所有权利。

Previous studies have shown that Alisol B 23-acetate (23ABA) had potent liver-protection effects, however, its roles and potential mechanisms in carbon tetrachloride (CCl4)-induced liver fibrosis remain to be determined. The present study aimed to investigate the effects of 23ABA on CCl4-induced liver fibrosis and tried to elucidate the underlying mechanisms by focusing on regulating of farnesoid X receptor (FXR). In vivo study found that 23ABA alleviated the CCl4-induced liver injury, and showed no obvious systemic toxicity on mice. 23ABA inhibited the collagen production, decreased sera levels of hyaluronic acid (HA) and procollagen type III (PC-III), lowered mRNA expression of α-smooth muscle actin (α-SMA), fibronectin, collagen I and collagen III in livers of mice. 23ABA inhibited the mRNA expressions and the sera levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α), as well as decreased the expression of cyclooxygenase 2 (COX-2) in fibrotic livers of mice. Besides, 23ABA decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased glutathione (GSH) level, enhanced activities of superoxide dismutase (SOD) and glutathione reductase (GR) as well as increased mRNA expression of nuclear factor-E2-related factor 2 (Nrf2), glutamate-cysteine ligase, catalytic subunit (GCLC) and glutamate-cysteine ligase, modifier subunit (GCLM). Further study showed that the anti-liver injury and anti-fibrotic effects of 23ABA were abrogated by FXR antagonist guggulsterone (GS) in vivo. In addition, the inhibition effects of 23ABA on liver inflammation and oxidative stress were also weakened by treatment with GS in CCl4-induced fibrotic mice livers. In conclusion, the protective effects of 23ABA against CCl4-induced liver injury and fibrosis, due to FXR-mediated regulation of liver inflammation and oxidative stress.Copyright © 2023 Elsevier B.V. All rights reserved.