Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.
Department of Gastrosplenic Diseases, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.
Mol Med Rep. 2024 Jul;30(1). doi: 10.3892/mmr.2024.13253. Epub 2024 May 24.
Astragaloside IV (AS‑IV) has various pharmacological effects, including antioxidant and immunoregulatory properties, which can improve myasthenia gravis (MG) symptoms. However, the potential mechanism underlying the effects of AS‑IV on MG remains to be elucidated. The present study aimed to investigate whether AS‑IV has a therapeutic effect on MG and its potential mechanism of action. By subcutaneously immunizing rats with R97‑116 peptide, an experimental autoimmune (EA) MG rat model was established. AS‑IV (40 or 80 mg/kg/day) treatment was then applied for 28 days after modeling. The results demonstrated that AS‑IV significantly ameliorated the weight loss, Lennon score and pathological changes in the gastrocnemius muscle of EAMG rats compared with the model group. Additionally, the levels of acetylcholine receptor antibody (AChR‑Ab) were significantly decreased, whereas mitochondrial function [ATPase and cytochrome c (Cyt‑C) oxidase activities] and ultrastructure were improved in the AS‑IV treated rats. Moreover, the mRNA and protein expression levels of phosphatase and tensin homolog‑induced putative kinase 1, Parkin, LC3II and Bcl‑2, key signaling molecules for mitophagy and apoptosis, were upregulated, whereas the mRNA and protein expression levels of p62, Cyt‑C, Bax, caspase 3 and caspase 9 were downregulated following AS‑IV intervention. In conclusion, AS‑IV may protect against EAMG in a rat model by modulating mitophagy and apoptosis. These findings indicated the potential mechanism underlying the effects of AS‑IV on MG and provided novel insights into treatment strategies for MG.
黄芪甲苷 (AS-IV) 具有多种药理作用,包括抗氧化和免疫调节特性,可改善重症肌无力 (MG) 症状。然而,AS-IV 对 MG 的作用机制仍有待阐明。本研究旨在探讨 AS-IV 对 MG 是否具有治疗作用及其潜在的作用机制。通过用 R97-116 肽皮下免疫大鼠,建立实验性自身免疫性 (EA) MG 大鼠模型。然后在建模后 28 天给予 AS-IV(40 或 80mg/kg/天)治疗。结果表明,与模型组相比,AS-IV 显著改善了 EAMG 大鼠的体重减轻、Lennon 评分和腓肠肌病理变化。此外,AS-IV 治疗组乙酰胆碱受体抗体 (AChR-Ab) 水平显著降低,而线粒体功能[三磷酸腺苷酶和细胞色素 c (Cyt-C) 氧化酶活性]和超微结构得到改善。此外,磷酸酶和张力蛋白同源物诱导的假定激酶 1、Parkin、LC3II 和 Bcl-2 的 mRNA 和蛋白表达水平上调,而 p62、Cyt-C、Bax、caspase 3 和 caspase 9 的 mRNA 和蛋白表达水平下调。总之,AS-IV 通过调节自噬和凋亡可能对 EAMG 大鼠模型起到保护作用。这些发现表明了 AS-IV 对 MG 作用的潜在机制,并为 MG 的治疗策略提供了新的思路。