Ophthalmology and ENT Teaching & Research Office, Jiangxi Medical College, Shangrao, 334000, China.
Pediatric Teaching & Research Office, Jiangxi Medical College, Shangrao, 334000, China.
J Physiol Investig. 2024 Jul 1;67(4):215-224. doi: 10.4103/ejpi.EJPI-D-24-00039. Epub 2024 Aug 29.
Diabetic retinopathy (DR) is one of the significant disabling outcomes of diabetes mellitus characterized by retinal microvascular damage, inflammation, and neuronal dysfunction. Allicin (Alc), a natural compound found in garlic, has garnered attention for its antioxidant and anti-inflammatory properties, positioning it as a potential therapeutic agent for DR. The aim of the present study was to investigate the therapeutic efficacy of Alc in DR management and elucidate its underlying mechanisms of action. We established a DR model in male Sprague-Dawley rats (n = 50, 200-250 g, 12 weeks old) using a high-fat diet for 8 weeks plus a low dose of streptozotocin administered at the start of the 4th week. The diabetic (Diab) animals were administered Alc (16 mg/kg/day, orally), either alone or in combination with mitochondrial division inhibitor-1 (Mdivi-1) as a mitophagy inhibitor, starting 28 days before tissue sampling. We evaluated histopathological changes, metabolic abnormalities associated with type 2 diabetes mellitus (T2DM), the expression of proteins regulating pyroptosis (NOD-like receptor family pyrin domain containing 3, cleaved-caspase 1, and gasdermin D-N terminal) and mitophagy (phosphatase and tensin homolog-induced kinase 1 [PINK1] and Parkin), as well as the levels of oxidative stress mediators and proinflammatory cytokines. Alc treatment effectively ameliorated histopathological changes and metabolic abnormalities associated with T2DM. It downregulated pyroptosis-related proteins, upregulated mitophagy-related proteins, reduced proinflammatory cytokine levels, and attenuated oxidative stress. Treatment with Mdivi-1 suppressed the beneficial effects of Alc. Our findings highlight the therapeutic potential of Alc in managing DR by targeting multiple pathophysiological pathways, including pyroptosis, inflammation, and oxidative stress. The observed antipyroptotic effects of Alc were partially mediated by the activation of the PINK1/parkin-mediated mitophagy pathway. Additional studies are necessary to thoroughly understand the therapeutic mechanisms of Alc and its viability as a treatment choice for DR.
糖尿病性视网膜病变 (DR) 是糖尿病的一种严重致残后果，其特征为视网膜微血管损伤、炎症和神经元功能障碍。大蒜中的天然化合物蒜素 (Alc) 因其抗氧化和抗炎特性而备受关注，有望成为 DR 的一种潜在治疗药物。本研究旨在探讨 Alc 在 DR 管理中的治疗效果，并阐明其作用机制。我们使用高脂饮食 8 周加第 4 周开始时给予低剂量链脲佐菌素在雄性 Sprague-Dawley 大鼠 (n = 50，200-250 g，12 周龄) 中建立 DR 模型。糖尿病 (Diab) 动物在组织取样前 28 天开始每天口服 16 mg/kg Alc，或与线粒体分裂抑制剂-1 (Mdivi-1) 联合使用，后者是一种自噬抑制剂。我们评估了组织病理学变化、与 2 型糖尿病 (T2DM) 相关的代谢异常、调节细胞焦亡的蛋白 (NOD 样受体家族 pyrin 结构域包含 3、裂解半胱氨酸天冬氨酸蛋白酶 1 和 gasdermin D-N 末端) 和自噬的表达 (磷酸酶和张力蛋白同源物诱导激酶 1 [PINK1] 和 Parkin)，以及氧化应激介质和促炎细胞因子的水平。Alc 治疗有效改善了与 T2DM 相关的组织病理学变化和代谢异常。它下调细胞焦亡相关蛋白，上调自噬相关蛋白，降低促炎细胞因子水平，减轻氧化应激。用 Mdivi-1 抑制 Alc 的有益作用。我们的研究结果强调了 Alc 通过靶向多个病理生理途径治疗 DR 的治疗潜力，包括细胞焦亡、炎症和氧化应激。观察到 Alc 的抗细胞焦亡作用部分是通过激活 PINK1/parkin 介导的自噬途径介导的。需要进一步研究以充分了解 Alc 的治疗机制及其作为 DR 治疗选择的可行性。
