AUTHOR=Zhang Yiwen , Huang Hong , Yao Caihong , Sun Xinran , He Qinghu , Choudharyc Muhammad Iqbal , Chen Shanguang , Liu Xinmin , Jiang Ning TITLE=Fresh Gastrodia elata Blume alleviates simulated weightlessness-induced cognitive impairment by regulating inflammatory and apoptosis-related pathways JOURNAL=Frontiers in Pharmacology VOLUME=Volume 14 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1173920 DOI=10.3389/fphar.2023.1173920 ISSN=1663-9812 ABSTRACT=In aerospace medicine, the influence of microgravity on cognition has always been a risk factor threatening astronauts' health. The traditional medicinal plant and food material, Gastrodia elata Blume, has been used as a therapeutic drug for neurological diseases for a long time due to its unique neuroprotective effect. To study the effect of fresh Gastrodia elata Blume (FG) on cognitive impairment caused by microgravity, hindlimb unloading (HU) was used to stimulate weightlessness in mice. The FG at the doses of 0.5 or 1.0 g/kg was daily administrated to the HU mice and behavior tests were conducted after four weeks of modeling to detect the cognitive state of animals. The behavioral results showed that FG therapy significantly improved the performance of mice in the object location recognition test, Step-Down test, and Morris Water Maze test, including short-term and long-term spatial memory. According to the biochemical test results, FG administration not only reduced serum factor levels of oxidative stress but also maintained the balance of pro-inflammatory and anti-inflammatory factors in the hippocampus, reversing the abnormal increase of NLRP3 and NF-κB. The apoptosis-related proteins were down-regulated which may be related to the activation of the PI3K/AKT/mTOR pathway by FG therapy, and the abnormal changes of synapse-related protein and glutamate neurotransmitter were corrected. These results identify the improvement effect of FG as a new application form of Gastrodia elata Blume on cognitive impairment caused by simulated weightlessness and advance our understanding of the mechanism of FG on the neuroprotective effect.