Jian-Yan-Ling capsules ameliorate cognitive impairment in mice with D-galactose-induced senescence and inhibit the oxidation-induced apoptosis of HT22 hippocampal cells by regulating the Nrf2-HO1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jian-Yan-Ling (JYL) capsule is a famous anti-aging Chinese patent medicine. It is applied mainly to delay senescence to improve cognition in aging individuals. However, the action mechanisms of JYL for improving cognition have not been determined.

AIM OF THE STUDY: We will evaluate the effect of the JYL capsule at improving the cognition of aging mice by improving oxidative stress in the hippocampus and exploring its action mechanism.

MATERIALS AND METHODS: A senescence mouse model was developed via intraperitoneal injection of D-galactose. The effect of the JYL capsule at improving the learning and memory abilities of mice was evaluated using the Morris water maze and novel object recognition tests. The apotosis of model mice hippocampus' were determined by TUNEL analysis. The antioxidant capacity of the JYL capsule was evaluated by determining the activities of antioxidant enzymes and expressions of oxidative products. The regulation of the Nrf2/HO-1 signaling pathway of the JYL capsule was evaluated by determining the expressions of related proteins via western blotting analysis. In vitro, H2 O2 -treated mouse hippocampal HT22 cells were used to evaluate the antioxidant capacity of JYL-containing rat serum by determining the cell viability, apoptotic level and expressions of related proteins.

RESULTS: JYL capsules enhanced the learning and memory abilities of model mice according to behavioral tests. The results of TUNEL analysis showed that the JYL capsule ameliorated hippocampal apoptosis in model mice. JYL capsules also exerted significant antioxidant capacity by increasing the activities of antioxidant enzymes while decreasing the levels of oxidative products both in the hippocampus and serum. The regulation of Nrf2/HO-1 pathway might contribute to the antioxidant function. In vitro, JYL-containing rat serum protected HT22 cells from H2 O2 induced oxidative stress. The apoptosis of HT22 cells was also attenuated by regulating the caspase and Nrf2/HO-1 signaling pathways.

CONCLUSIONS: The amelioration of neuronal oxidative stress of hippocampus might contribute to the D-galactose-induced cognition impairment of senescence mice. These findings provide evidence for the application of JYL capsules to enhance cognition in aging individuals.