Genetics and Molecular Biology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt.
Biology Department, King Khalid Military Academy, P.O. Box 22140, Riyadh, 11495, Saudi Arabia.
Mol Biol Rep. 2024 Aug 8;51(1):897. doi: 10.1007/s11033-024-09805-x.
Diabetes mellitus (DM) is a global metabolic problem. Several factors including hyperglycemia, oxidative stress, and inflammation play significant roles in the development of DM complications. Apoptosis is also an essential event in DM pathophysiology, -with B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) determining apoptotic susceptibility. The present study aimed to elucidate the protective effects of two doses of taxifolin (TXF) on liver damage in diabetic rats and explore the possible mechanisms of action.
DM was induced in eighteen rats through intraperitoneal injections of 50 mg/kg streptozotocin and 110 mg/kg nicotinamide. Diabetic rats received daily oral intubation of 25 and 50 mg/kg TXF for 3 months. In the untreated diabetic group, there was a significant increase in fasting and postprandial glucose levels, glycosylated hemoglobin A1C (HbA1c), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while insulin and adiponectin levels decreased significantly. Both TXF doses mitigated hyperglycemia, regulated cytokine production, and increased insulin level. Gene expressions and protein levels of Bax, caspase 3, and cytochrome c were significantly increased, while Bcl-2 was significantly decreased in the livers of diabetic rats, effects that were significantly ameliorated after TXF treatment. The results of the TUNEL assay supported the apoptotic pathway. Additionally, TXF significantly decreased lipid peroxidation and enhanced antioxidant enzyme activity in diabetic rats. Liver enzymes and histopathological changes also showed improvement.
TXF mitigated diabetes-associated hepatic damage by reducing hyperglycemia, oxidative stress, inflammation, and modulating anti-/pro-apoptotic genes and proteins. A dose of 50 mg/kg TXF was more effective than 25 mg/kg and is recommended for consumption.
糖尿病（DM）是一种全球性的代谢问题。多种因素，包括高血糖、氧化应激和炎症，在 DM 并发症的发展中起着重要作用。细胞凋亡也是 DM 病理生理学中的一个重要事件，B 细胞淋巴瘤 2（Bcl-2）和 Bcl-2 相关 X（Bax）决定了细胞凋亡的易感性。本研究旨在阐明两种剂量的漆黄素（TXF）对糖尿病大鼠肝损伤的保护作用，并探讨其可能的作用机制。
通过腹腔注射 50mg/kg 链脲佐菌素和 110mg/kg 烟酰胺将 18 只大鼠诱导为糖尿病。糖尿病大鼠每天口服给予 25 和 50mg/kg TXF 治疗 3 个月。在未治疗的糖尿病组中，空腹和餐后血糖水平、糖化血红蛋白 A1C（HbA1c）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）显著升高，而胰岛素和脂联素水平显著降低。两种 TXF 剂量均能缓解高血糖，调节细胞因子产生，并增加胰岛素水平。Bax、caspase 3 和细胞色素 c 的基因表达和蛋白水平在糖尿病大鼠肝脏中显著升高，而 Bcl-2 显著降低，经 TXF 治疗后这些变化明显改善。TUNEL 检测结果支持凋亡途径。此外，TXF 还显著降低了糖尿病大鼠的脂质过氧化作用，并增强了抗氧化酶的活性。肝酶和组织病理学变化也得到改善。
TXF 通过降低高血糖、氧化应激、炎症以及调节抗/促凋亡基因和蛋白来减轻与糖尿病相关的肝损伤。50mg/kg TXF 的剂量比 25mg/kg 更有效，建议使用。
