Department of Biotechnology, Medical Biotechnology Laboratory, Guru Nanak Dev University, Amritsar, Amritsar, Punjab, 143005, India.
BMC Complement Altern Med. 2019 Aug 15;19(1):217. doi: 10.1186/s12906-019-2635-0.
Systemic inflammation driven neuroinflammation is an event which correlates with pathogenesis of several neurodegenerative diseases. Therefore, targeting peripheral and central inflammation simultaneously could be a promising approach for the management of these diseases. Nowadays, herbal medicines are emerging as potent therapeutics against various brain pathologies. Therefore, in this contemporary study, the neuroprotective activity of Ashwagandha (Withania somnifera) was elucidated against the inflammation associated neurodegeneration and cognitive impairments induced by systemic LPS administration using in vivo rat model system.
To achieve this aim, young adult wistar strain male albino rats were randomized into four groups: (i) Control, (ii) LPS alone, (iii) LPS + ASH-WEX, (iv) ASH-WEX alone. Post regimen, the animals were subjected to Rotarod, Narrow Beam Walking and Novel Object Recognition test to analyze their neuromuscular coordination, working memory and learning functions. The rats were then sacrificed to isolate the brain regions and expression of proteins associated with synaptic plasticity and cell survival was studied using Western blotting and Quantitative real time PCR. Further, neuroprotective potential of ASH-WEX and its active fraction (FIV) against inflammatory neurodegeneration was studied and validated using in vitro model system of microglial conditioned medium-treated neuronal cultures and microglial-neuronal co-cultures.
Orally administered ASH-WEX significantly suppressed the cognitive and motor-coordination impairments in rats. On the molecular basis, ASH-WEX supplementation also regulated the expression of various proteins involved in synaptic plasticity and neuronal cell survival. Since microglial-neuronal crosstalk is crucial for maintaining CNS homeostasis, the current study was further extended to ascertain whether LPS-mediated microglial activation caused damage to neurons via direct cell to cell contact or through secretion of inflammatory mediators. ASH-WEX and FIV pretreatment was found to restore neurite outgrowth and protect neurons from apoptotic cell death caused by LPS-induced neuroinflammation in both activated microglial conditioned medium-treated neuronal cultures as well as microglial-neuronal co-cultures.
This extensive study using in vivo and in vitro model systems provides first ever pre-clinical evidence that ASH-WEX can be used as a promising natural therapeutic remedial for the prevention of neurodegeneration and cognitive impairments associated with peripheral inflammation and neuroinflammation.
系统性炎症驱动的神经炎症是与多种神经退行性疾病发病机制相关的事件。因此，同时针对外周和中枢炎症可能是这些疾病治疗的一种有前途的方法。如今，草药作为针对各种脑病理学的有效治疗方法正在出现。因此，在这项当代研究中，使用体内大鼠模型系统，阐明了 Ashwagandha（Withania somnifera）对系统 LPS 给药引起的炎症相关神经退行性变和认知障碍的神经保护活性。
为了实现这一目标，将年轻成年 Wistar 品系雄性白化大鼠随机分为四组：（i）对照组，（ii）LPS 单独组，（iii）LPS+ASH-WEX 组，（iv）ASH-WEX 单独组。方案后，动物接受旋转棒、窄束行走和新物体识别测试，以分析它们的神经肌肉协调、工作记忆和学习功能。然后处死大鼠以分离大脑区域，并使用 Western blot 和定量实时 PCR 研究与突触可塑性和细胞存活相关的蛋白质表达。此外，使用体外小胶质细胞条件培养基处理神经元培养物和小胶质细胞-神经元共培养物的模型系统研究和验证了 ASH-WEX 及其活性部分（FIV）对炎症性神经退行性变的神经保护潜力。
口服给予 ASH-WEX 可显著抑制大鼠的认知和运动协调障碍。从分子基础上讲，ASH-WEX 补充还调节了参与突触可塑性和神经元细胞存活的各种蛋白质的表达。由于小胶质细胞-神经元串扰对于维持中枢神经系统内稳态至关重要，因此本研究进一步扩展，以确定 LPS 介导的小胶质细胞激活是否通过直接细胞间接触或通过分泌炎症介质对神经元造成损害。发现 ASH-WEX 和 FIV 预处理可恢复由 LPS 诱导的神经炎症引起的神经元突起生长，并防止神经元发生凋亡性细胞死亡，这在激活的小胶质细胞条件培养基处理的神经元培养物以及小胶质细胞-神经元共培养物中均如此。
这项使用体内和体外模型系统的广泛研究首次提供了临床前证据，表明 ASH-WEX 可用作预防与外周炎症和神经炎症相关的神经退行性变和认知障碍的有前途的天然治疗方法。
