松香酸通过调节 Nrf2/HO-1 轴减轻炎症和铁死亡来抑制对乙酰氨基酚诱导的肝损伤。

Abietic acid inhibits acetaminophen-induced liver injury by alleviating inflammation and ferroptosis through regulating Nrf2/HO-1 axis.

机构信息

Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

出版信息

Int Immunopharmacol. 2023 May;118:110029. doi: 10.1016/j.intimp.2023.110029. Epub 2023 Mar 22.

DOI:10.1016/j.intimp.2023.110029

PMID:36963265

Abstract

Abietic acid has been known to exhibit anti-inflammatory activity. This study was designed to investigate the protective effects of abietic acid on acetaminophen (APAP)-induced liver injury. The data demonstrated that abietic acid significantly ameliorated APAP-induced liver pathological changes, TNF-α and IL-1β production. APAP could increase malondialdehyde (MDA) and Fe levels, and decrease ATP and glutathione (GSH) levels, as well as glutathione peroxidase 4 (GPX4) and xCT expression. However, these changes induced by APAP were prevented by abietic acid, indicating abietic acid could inhibit APAP-induced ferroptosis. Furthermore, abietic acid inhibited APAP-induced NF-κB activation and increased the expression of Nrf2 and HO-1. Additionally, the inhibitory effects of abietic acid on APAP-induced liver injury were prevented in Nrf2 mice. In vitro, the inhibition of abietic acid on APAP-induced inflammation and ferroptosis were reversed when Nrf2 was knockdown. In summary, abietic acidexhibited a therapeutic effectagainst liver injury by attenuating inflammation and ferroptosis.

摘要

松香酸具有抗炎活性。本研究旨在探讨松香酸对乙酰氨基酚（APAP）诱导的肝损伤的保护作用。研究数据表明，松香酸可显著改善 APAP 诱导的肝组织病理变化，降低 TNF-α 和 IL-1β 的产生。APAP 可增加丙二醛（MDA）和铁水平，降低 ATP 和谷胱甘肽（GSH）水平，以及谷胱甘肽过氧化物酶 4（GPX4）和 xCT 的表达。然而，这些由 APAP 诱导的变化被松香酸所阻止，表明松香酸可抑制 APAP 诱导的铁死亡。此外，松香酸抑制了 NF-κB 的激活，并增加了 Nrf2 和 HO-1 的表达。此外，在 Nrf2 敲除小鼠中，松香酸对 APAP 诱导的肝损伤的抑制作用被阻断。在体外，当 Nrf2 被敲低时，松香酸对 APAP 诱导的炎症和铁死亡的抑制作用被逆转。总之，松香酸通过减轻炎症和铁死亡发挥了对肝损伤的治疗作用。