Activation of SIRT1 by silibinin improved mitochondrial health and alleviated the oxidative damage in experimental diabetic neuropathy and high glucose-mediated neurotoxicity.

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM Archives of Physiology and Biochemistry Pub Date : 2024-08-01 Epub Date: 2022-08-09 DOI:10.1080/13813455.2022.2108454

Islauddin Khan, Kumari Preeti, Rahul Kumar, Dharmendra Kumar Khatri, Shashi Bala Singh

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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: SBN has shown neuroprotective potential in DPN through SIRT1 activation and antioxidant mechanism.

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在实验性糖尿病神经病变和高糖介导的神经毒性中，西利宾激活 SIRT1 可改善线粒体健康，减轻氧化损伤。

背景：Silibinin (SBN)是一种sirtuin 1 (SIRT1)激活剂，其抗炎活性已在许多炎症性疾病中得到评估。然而，它在糖尿病诱发的周围神经病变（DPN）中的作用仍然未知。激活 SIRT1 可通过改善线粒体的生物生成和有丝分裂来恢复神经功能：方法：用 55 毫克/千克剂量的链脲佐菌素（STZ）诱导雄性 SD 大鼠发生 DPN，用 30 毫摩尔（高糖）葡萄糖诱导 Neuro2A 细胞发生神经毒性。对神经行为（神经传导速度和神经血流量）进行了免疫印迹、免疫组织化学和免疫细胞化学分析，以评估蛋白质的表达及其在细胞中的定位：结果：为期两周的 SBN 治疗改善了神经行为症状、SIRT1、PGC-1α 和 TFAM 在坐骨神经和受 HG 损伤的 N2A 细胞中的表达。它还能通过上调 PARL、PINK1、PGAM5 和 LC3 水平维持有丝分裂，并通过上调 Nrf2 提供抗氧化防御：结论：通过激活 SIRT1 和抗氧化机制，SBN 对 DPN 具有神经保护潜力。

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来源期刊

Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY

CiteScore

6.90

自引率

3.30%

发文量

期刊介绍： Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.