Gastrodia elata Blume (Tianma) extract mitigates simulated microgravity-induced oxidative stress and enhance learning and memory in Caenorhabditis elegans.

Microgravity during long-duration spaceflights promotes oxidative damage, impairs mitochondrial efficiency, and induces neurodegeneration, highlighting the need for safe countermeasures. Gastrodia elata (Tianma) is a traditional medicinal herb with known antioxidant and neuroprotective properties that has not yet been examined under microgravity-analog conditions. The main aim of this study was to evaluate whether Tianma mitigates oxidative, mitochondrial, and neurobehavioral deficits induced by simulated microgravity (SM) in Caenorhabditis elegans (C. elegans). N2, TJ356 (DAF-16::GFP), and BZ555 (dat-1p::GFP) worms were treated with Tianma extract or vehicle for 72 h and exposed to simulated microgravity for 24 h thereafter. We quantified multiple functional and molecular endpoints related to organismal health, redox balance, mitochondrial function, dopaminergic neuron integrity, and stress resistance to determine the mitigative effect of Tianma on SM. SM significantly disrupts organismal and cellular homeostasis, as evidenced by reduced locomotion, pharyngeal pumping, associative learning and memory with butanone, dopamine-dependent basal slowing, and reduced lifespan. These functional deficits were accompanied by elevated oxidative damage, diminished antioxidant enzyme activities, mitochondrial depolarization and ATP depletion, enhanced DAF-16 nuclear translocation, upregulation of antioxidant, heat-shock, and mitochondrial stress-response genes, and progressive dopaminergic neuron loss. Tianma treatment restored behavioral performance, extended lifespan, normalized oxidative markers and enzyme activities, preserved mitochondrial function, limited DAF-16 nuclear accumulation, attenuated stress-gene induction, protected dopaminergic neurons, and enhanced stress resistance. These findings indicate that Tianma provides integrated antioxidant, mitochondrial, and neuroprotective effects under simulated microgravity and merit further evaluation as a potential countermeasure against spaceflight-associated oxidative and neurodegenerative stress.