Defense Institute of High Altitude Research, Defense Research and Development Organization, Leh-Ladakh, India.
Department of Biotechnology, Techno India University, Salt Lake City, India.
High Alt Med Biol. 2019 Sep;20(3):279-292. doi: 10.1089/ham.2019.0011.
Exposure to hypobaric hypoxia (HH) has been reported to cause neurodegeneration and memory impairment. , , and , the indigenous plants of Indian Trans-Himalaya are widely used in traditional Tibetan and Amchi system of medicine. These are rich sources of diverse bioactive metabolites having prophylactic and therapeutic uses against a wide array of neurodegenerative diseases. The objective of this study was to elucidate the prophylactic and neuroprotective efficacy of formulated phytococktail (PC) against simulated HH-induced neurodegeneration in male Sprague Dawley (SD) rats. A PC containing fruit pulp, fruit pulp, and dry root extract (100:50:1) was formulated. The neuroprotective efficacy of PC was evaluated in male SD rats following exposure to 7 day HH at simulated altitude (25,000 ft, 282 mm Hg). Rats were divided into four groups viz., normoxia group (NOR), normoxic group treated with PC (NORPC), 7 day hypoxic group treated with vehicle (7DH), and 7 day hypoxic group treated with PC (7DHPC). Memory impairment and neuromorphological alterations were measured. Targeted protein expression was analyzed by immunoblotting study. PC supplementation significantly reduced the oxidative stress markers during exposure to HH. Spatial memory impairment by HH was significantly ameliorated by PC. HH-induced augmented pyknosis, decreased dendritic arborization, and increased Hoechst-positive neurons in hippocampal CA3 region were significantly ameliorated by PC. Immunoblotting study showed upregulation of BDNF and TrkB expression by PC. PC also prevented the hippocampal neurodegeneration by activating the PI3K/AKT signaling pathway, which leads to GSK-3β inactivation by its phosphorylation and alleviation of hippocampal Caspase3 expression leading to inhibition of apoptotic neuronal cell death. The present study advocates the potential role of PC as an effective neuroprotective supplement in preventing HH-induced neurodegeneration. Activation of the PI3K/Akt pathway through BDNF/TrkB interaction following PC supplementation after exposure to HH inhibits hippocampal neuronal apoptosis and memory impairment.
暴露于低气压缺氧（HH）已被报道可导致神经退行性变和记忆损伤。喜马拉雅山西部的土生土长的植物，广泛应用于传统的藏医和阿育吠陀医学体系。这些植物是具有预防和治疗多种神经退行性疾病的多种生物活性代谢物的丰富来源。本研究的目的是阐明配方植物鸡尾酒（PC）对雄性 Sprague Dawley（SD）大鼠模拟 HH 诱导的神经退行性变的预防和神经保护作用。 包含 果肉、 果肉和 干根提取物（100:50:1）的 PC 被配方化。在暴露于模拟海拔 25000 英尺（282 毫米汞柱）的 7 天 HH 后，在雄性 SD 大鼠中评估了 PC 的神经保护作用。大鼠分为四组：常氧组（NOR）、常氧组给予 PC（NORPC）、7 天低氧组给予载体（7DH）和 7 天低氧组给予 PC（7DHPC）。测量记忆障碍和神经形态改变。通过免疫印迹研究分析靶向蛋白表达。 PC 补充剂在暴露于 HH 时显著降低氧化应激标志物。PC 显著改善 HH 引起的空间记忆障碍。HH 诱导的海马 CA3 区核固缩增加、树突分支减少和 Hoechst 阳性神经元增加被 PC 显著改善。免疫印迹研究显示，PC 上调 BDNF 和 TrkB 的表达。PC 还通过激活 PI3K/AKT 信号通路来防止海马神经退行性变，从而通过磷酸化使其使 GSK-3β失活，并减轻海马 Caspase3 表达，从而抑制凋亡性神经元细胞死亡。 本研究提倡 PC 作为一种有效的神经保护补充剂，在预防 HH 诱导的神经退行性变中的潜在作用。暴露于 HH 后补充 PC 通过 BDNF/TrkB 相互作用激活 PI3K/Akt 途径，抑制海马神经元凋亡和记忆损伤。
