Ministry of Health, Kuwait City, Kuwait.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
CNS Neurosci Ther. 2023 Oct;29(10):3068-3080. doi: 10.1111/cns.14249. Epub 2023 May 11.
Oxidative stress mediates the pathophysiology of diabetic neuropathy (DN) with activation of apoptotic pathway and reduction of autophagy. Arctigenin (ARC) is a natural lignan isolated from some plants of the Asteraceae family that shows antioxidant property. The present study aimed to explore the mechanistic neuroprotective effect of ARC on animal model for DN.
DN was induced using streptozotocin (STZ) at a dose of 45 mg/kg, i.p, for five consecutive days and ARC was administered orally (25 or 50 mg) for 3 weeks. The mechanical sensitivity and thermal latency were determined using von Frey and hotplate, respectively. Beclin, p62, and LC3 were detected as markers for autophagy by western blot. Levels of reduced glutathione, lipid peroxides, and activities of catalase and superoxide dismutase were detected as readout for oxidative stress. Apoptotic parameters and histopathological changes were revealed in all experimental groups.
The present study showed deterioration of the function and structure of neurons as a result of hyperglycemia. Oxidative stress and impaired autophagy were observed in diabetic neurons as well as the activation of apoptotic pathway. ARC improved the behavioral and histopathological changes of diabetic mice. ARC combated oxidative stress through diminishing lipid peroxidation and improving the activity of antioxidant enzymes. This was concomitant by reducing the biomarkers of apoptosis. ARC augmented the expression of Beclin and LC3 while it lessened the expression of p62 indicating the activation of autophagy. These findings suggest that ARC can ameliorate DN by combating apoptosis and oxidative stress and improving autophagy.
氧化应激介导糖尿病神经病变（DN）的病理生理学，激活凋亡途径并减少自噬。牛蒡子苷元（ARC）是一种从菊科某些植物中分离出来的天然木脂素，具有抗氧化特性。本研究旨在探讨 ARC 对糖尿病动物模型的神经保护作用的机制。
用链脲佐菌素（STZ）以 45mg/kg，腹腔注射，连续 5 天诱导 DN，并口服 ARC（25 或 50mg）3 周。使用 von Frey 和热板分别测定机械敏感性和热潜伏期。通过 Western blot 检测自噬标志物 Beclin、p62 和 LC3。检测还原型谷胱甘肽、脂质过氧化物、过氧化氢酶和超氧化物歧化酶的活性作为氧化应激的指标。在所有实验组中揭示了凋亡参数和组织病理学变化。
本研究表明，高血糖导致神经元的功能和结构恶化。糖尿病神经元中存在氧化应激和自噬受损，以及凋亡途径的激活。ARC 改善了糖尿病小鼠的行为和组织病理学变化。ARC 通过减少脂质过氧化和改善抗氧化酶的活性来对抗氧化应激。这与凋亡标志物的减少同时发生。ARC 增加了 Beclin 和 LC3 的表达，同时减少了 p62 的表达，表明自噬的激活。这些发现表明，ARC 通过对抗凋亡和氧化应激以及改善自噬来改善糖尿病神经病变。
