Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
Arch Physiol Biochem. 2024 Aug;130(4):420-436. doi: 10.1080/13813455.2022.2108454. Epub 2022 Aug 9.
Silibinin (SBN), a sirtuin 1 (SIRT1) activator, has been evaluated for its anti-inflammatory activity in many inflammatory diseases. However, its role in diabetes-induced peripheral neuropathy (DPN) remains unknown. The SIRT1 activation convalesces nerve functions by improving mitochondrial biogenesis and mitophagy.
DPN was induced by streptozotocin (STZ) at a dose of 55 mg/kg, i.p. in the male SD rats whereas neurotoxicity was induced in Neuro2A cells by 30 mM (high glucose) glucose. Neurobehavioural (nerve conduction velocity and nerve blood flow) western blot, immunohistochemistry, and immunocytochemistry were performed to evaluate the protein expression and their cellular localisation.
Two-week SBN treatment improved neurobehavioural symptoms, SIRT1, PGC-1α, and TFAM expression in the sciatic nerve and HG insulted N2A cells. It has also maintained the mitophagy by up-regulating PARL, PINK1, PGAM5, LC3 level and provided antioxidant defence by upregulating Nrf2.
SBN has shown neuroprotective potential in DPN through SIRT1 activation and antioxidant mechanism.
水飞蓟宾（SBN）是一种 Sirtuin 1（SIRT1）激活剂，已在许多炎症性疾病中评估其抗炎活性。然而，其在糖尿病性周围神经病变（DPN）中的作用尚不清楚。SIRT1 的激活通过改善线粒体生物发生和线粒体自噬来恢复神经功能。
雄性 SD 大鼠腹腔注射链脲佐菌素（STZ）（剂量为 55mg/kg）诱导 DPN，而神经毒性则由 30mM（高葡萄糖）葡萄糖诱导的 Neuro2A 细胞产生。通过神经行为学（神经传导速度和神经血流）western blot、免疫组织化学和免疫细胞化学来评估蛋白表达及其细胞定位。
SBN 治疗 2 周可改善坐骨神经中的神经行为症状、SIRT1、PGC-1α 和 TFAM 表达以及 HG 损伤的 N2A 细胞。它还通过上调 PARL、PINK1、PGAM5 和 LC3 水平维持线粒体自噬，并通过上调 Nrf2 提供抗氧化防御。
SBN 通过 SIRT1 激活和抗氧化机制显示出在 DPN 中的神经保护潜力。
