Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China; Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
Biochem Biophys Res Commun. 2022 Apr 30;602:105-112. doi: 10.1016/j.bbrc.2022.03.011. Epub 2022 Mar 3.
Amygdalin is a natural compound from Bitter Apricot Seed which is reported to have anti-inflammatory activity. Acetaminophen (APAP) resulted in drug-induced liver injury is the main cause of acute liver failure (ALI) worldwide and only N-acetylcysteine is the accepted detoxification drug. However, there is no effective medicine to perfect the hepatocyte death and secondary inflammation injury. In this study, we aim to investigate the protective effect of Amygdalin in the APAP-induced acute liver failure mice model. We establish the ALI model via intraperitoneal APAP injection and mice were treated with Amygdalin with intraperitoneal injection. We detected liver enzyme and histological change to evaluate the liver injury. We measured oxidative damage markers and inflammatory cell infiltration of liver tissues. At last, we investigated the mechanism of Amygdalin on protecting hepatocytes. Results showed that Amygdalin reduced ALT/AST level and decreased necrotic area of liver tissue. In addition, Amygdalin reduced the count of MPO+(neutrophils) and F4/80+(macrophages) of the liver and inhibited IL-6, TNF-a, and IL-1b expression. Amygdalin reduced liver SOD and MDA levels and increased Nrf2/NQO1/HO1 protein expression. Moreover, Amygdalin reduced TUNEL+ and P-MLKL + staining cells in liver tissue. Mechanically, Amygdalin promoted phosphorylation of AKT and suppressed JNK/RIP3/MLKL signaling.
苦杏仁苷是苦杏仁中的一种天然化合物，据报道具有抗炎活性。对乙酰氨基酚（APAP）导致的药物性肝损伤是全世界急性肝衰竭（ALI）的主要原因，只有 N-乙酰半胱氨酸是公认的解毒药物。然而，目前尚无有效的药物来完善肝细胞死亡和继发性炎症损伤。在本研究中，我们旨在研究苦杏仁苷在 APAP 诱导的急性肝衰竭小鼠模型中的保护作用。我们通过腹腔内注射 APAP 建立 ALI 模型，并用腹腔内注射苦杏仁苷对小鼠进行治疗。我们检测了肝酶和组织学变化，以评估肝损伤。我们测量了肝组织的氧化损伤标志物和炎症细胞浸润。最后，我们研究了苦杏仁苷保护肝细胞的机制。结果表明，苦杏仁苷降低了 ALT/AST 水平，减少了肝组织的坏死面积。此外，苦杏仁苷减少了肝组织中 MPO+（中性粒细胞）和 F4/80+（巨噬细胞）的计数，并抑制了 IL-6、TNF-a 和 IL-1b 的表达。苦杏仁苷降低了肝 SOD 和 MDA 水平，增加了 Nrf2/NQO1/HO1 蛋白表达。此外，苦杏仁苷减少了肝组织中 TUNEL+和 P-MLKL+染色细胞。在机制上，苦杏仁苷促进了 AKT 的磷酸化，并抑制了 JNK/RIP3/MLKL 信号通路。
