Medical Biotechnology Laboratory, Department of Biotechnology, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
Neuromolecular Med. 2018 Sep;20(3):343-362. doi: 10.1007/s12017-018-8497-7. Epub 2018 May 30.
Reactive gliosis, microgliosis, and subsequent secretion of various inflammatory mediators like cytokines, proteases, reactive oxygen, and nitrogen species are the suggested key players associated with systemic inflammation-driven neuroinflammation and cognitive impairments in various neurological disorders. Conventionally, non-steroidal anti-inflammatory drugs are prescribed to suppress inflammation but due to their adverse effects, their usage is not well accepted. Natural products are emerging better therapeutic agents due to their affordability and inherent pleiotropic biological activities. In Ayurveda, Ashwagandha (Withania somnifera) is well known for its immunomodulatory properties. The current study is an extension of our previous report on in vitro model system and was aimed to investigate anti-neuroinflammatory potential of water extract from the Ashwagandha leaves (ASH-WEX) against systemic LPS-induced neuroinflammation and associated behavioral impairments using in vivo rat model system. Oral feeding of ASH-WEX for 8 weeks significantly ameliorated the anxiety-like behavior as evident from Elevated plus maze test. Suppression of reactive gliosis, inflammatory cytokines production like TNF-α, IL-1β, IL-6, and expression of nitro-oxidative stress enzymes like iNOS, COX2, NOX2 etc were observed in ASH-WEX-treated animals. NFκB, P38, and JNK MAPKs pathways analysis showed their involvement in inflammation suppression which was further confirmed by inhibitor studies. The current study provides first ever preclinical evidence and scientific validation that ASH-WEX exhibits the anti-neuroinflammatory potential against systemic LPS-induced neuroinflammation and ameliorates associated behavioral abnormalities. Aqueous extract from Ashwagandha leaves and its active phytochemicals may prove to be promising candidates to prevent neuroinflammation associated with various neuropathologies.
反应性神经胶质增生、小胶质细胞增生以及随后各种炎症介质的分泌，如细胞因子、蛋白酶、活性氧和氮物种，被认为是与全身炎症驱动的神经炎症和各种神经紊乱认知障碍相关的关键因素。传统上，非甾体抗炎药被开处用于抑制炎症，但由于其不良反应，其使用并不被广泛接受。天然产物由于其价格合理和固有的多效生物活性，正在成为更好的治疗药物。在阿育吠陀医学中，南非醉茄（Withania somnifera）以其免疫调节特性而闻名。本研究是我们之前关于体外模型系统报告的延伸，旨在使用体内大鼠模型系统研究南非醉茄叶水提物（ASH-WEX）对全身 LPS 诱导的神经炎症和相关行为障碍的抗炎作用。8 周的口服 ASH-WEX 喂养显著改善了焦虑样行为，如高架十字迷宫测试所示。在 ASH-WEX 治疗的动物中观察到反应性神经胶质增生抑制、TNF-α、IL-1β、IL-6 等炎症细胞因子的产生以及 iNOS、COX2、NOX2 等硝基氧化应激酶的表达。NFκB、P38 和 JNK MAPKs 通路分析表明它们参与了炎症抑制，抑制剂研究进一步证实了这一点。本研究首次提供了临床前证据和科学验证，即 ASH-WEX 对全身 LPS 诱导的神经炎症具有抗炎作用，并改善了相关的行为异常。南非醉茄叶的水提物及其活性植物化学物质可能被证明是预防各种神经病理学相关神经炎症的有前途的候选药物。
