Department of Pharmacology, ISF College of Pharmacy affiliated to I.K Gujral Punjab Technical University, Jalandhar, 142001, Punjab, India.
Department of Pharmaceutical Sciences, School of Health Science & Technology, UPES, Dehradun, India.
J Mol Histol. 2024 Aug;55(4):599-625. doi: 10.1007/s10735-024-10217-1. Epub 2024 Jul 23.
Today, we critically need alternative therapeutic options for chemotherapy-induced cognitive impairment (CICI), often known as chemo brain. Mitochondrial dysfunction and oxidative stress are two of the primary processes that contribute to the development of chemobrain. Therefore, the purpose of this study was to investigate how CoQ10 and berberine shield neurons from chemotherapy-induced damage in in-vitro studies and memory loss in vivo studies. For the in-vitro investigation, we employed SH-SY5Y cell lines, and for the in-vivo study, we used female Swiss albino mice divided into seven different groups. Data from in-vitro studies revealed that treatment with coenzyme Q10 (CoQ10) and berberine improved chemotherapy-induced toxicity by reducing mitochondrial and total cellular ROS, as well as apoptosis-elicited markers (caspase 3 and 9). CoQ10 and berberine therapy inhibited the nuclear translocation of NF-κB and, consequently, the subsequent expressions of NLRP3 and IL-1β, implying the prevention of inflammasome formation. Furthermore, CoQ10 and berberine therapy boosted Nrf2 levels. This is a regulator for cellular resistance to oxidants. The in vivo results showed that treatment with CoQ10 (40 mg/kg) and berberine (200 mg/kg) improved the behavioral alterations induced by CAF (40/4/25 mg/kg) in both the Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests. Furthermore, biochemical and molecular evidence revealed the antioxidant, mitochondrial restorative, and anti-inflammatory potential of CoQ10 (40 mg/kg) and berberine (200 mg/kg) against CAF (40/4/25 mg/kg) subjected mice. In addition, the histological analysis using H&E staining and transmission electron microscopy (for mitochondrial morphology) showed that mice treated with the cocktails had an increased number of healthy neurons with intact mitochondria and a reduced presence of autophagic vacuoles in the hippocampal region of the brain. These findings back up our theory about this novel cocktail method for CAF-induced cognitive impairment.
今天，我们迫切需要治疗化疗引起的认知障碍（CICI）的替代疗法，通常称为化疗脑。线粒体功能障碍和氧化应激是导致化疗脑发展的两个主要过程。因此，本研究旨在探讨辅酶 Q10 和小檗碱如何在体外研究中保护神经元免受化疗引起的损伤，以及在体内研究中防止记忆丧失。在体外研究中，我们使用了 SH-SY5Y 细胞系，在体内研究中，我们使用了雌性瑞士白化病小鼠，将其分为七个不同的组。体外研究数据显示，用辅酶 Q10（CoQ10）和小檗碱治疗可通过降低线粒体和总细胞 ROS 以及凋亡诱导标志物（caspase 3 和 9）来改善化疗引起的毒性。CoQ10 和小檗碱治疗抑制了 NF-κB 的核易位，从而阻止了 NLRP3 和 IL-1β的随后表达，表明抑制了炎症小体的形成。此外，CoQ10 和小檗碱治疗可提高 Nrf2 水平。这是细胞抵抗氧化剂的调节剂。体内结果表明，用 CoQ10（40mg/kg）和小檗碱（200mg/kg）治疗可改善 CAF（40/4/25mg/kg）引起的行为改变，包括 Morris 水迷宫（MWM）和新物体识别（NOR）测试。此外，生化和分子证据表明，CoQ10（40mg/kg）和小檗碱（200mg/kg）对 CAF（40/4/25mg/kg）处理的小鼠具有抗氧化、线粒体修复和抗炎作用。此外，使用 H&E 染色和透射电子显微镜（用于线粒体形态）的组织学分析表明，用鸡尾酒治疗的小鼠大脑海马区的健康神经元数量增加，线粒体完整，自噬空泡减少。这些发现支持了我们关于 CAF 诱导的认知障碍的这种新鸡尾酒方法的理论。
