Effect of Hong Huang Tang on memory enhancement and mitigation of microgravity-induced oxidative stress in C. elegans

Ziziphus jujuba Mill. (ZJ) is a traditional medicinal plant known for its antioxidant, anti-inflammatory, and neuroprotective properties, yet its role in learning and cognitive regulation remains insufficiently explored. Huang Jing (Polygonatum sibiricum), a Qi- and Yin-tonifying herb in Traditional Chinese Medicine, has historically been used to combat fatigue, support brain function, delay aging, and regulate metabolic balance. In this study, we evaluated the neuroprotective and antioxidant effects of the combined formulation Hong Huang Tang in Caenorhabditis elegans under simulated microgravity conditions. Behavioral assays, including lifespan, chemotaxis-based learning, pharyngeal pumping, head thrashing, and body bending, were performed to assess cognitive and neuromuscular function. Mitochondrial health and oxidative stress markers were quantified, alongside expression of antioxidant defense genes. DAF-16::GFP localization and sod-3 expression were analyzed to determine involvement of Insulin/IGF-1 signaling. Additionally, neuroprotection against 6-hydroxydopamine-induced dopaminergic degeneration was assessed. Simulated microgravity triggered oxidative stress, mitochondrial dysfunction, reduced lifespan, impaired learning, and neuromuscular decline. Treatment with 2 mg/mL Hong Huang Tang significantly reversed these effects, restoring mitochondrial function, enhancing antioxidant capacity, and alleviating neurodegeneration. These findings support Hong Huang Tang as a promising therapeutic candidate for oxidative stress-related cognitive decline and neurodegenerative disorders.

Caenorhabditis elegans; Ziziphus jujuba Mill.; Antioxidant activity; DAF-16/insulin signalling; Huang Jing; Learning and memory; Mitochondrial dysfunction; Neuroprotection; Simulated microgravity.