Neuroprotection and safety profile of Astragalus membranaceus extract TA-65 in neonatal hypoxic-ischemic brain damage by activating mitochondrial telomerase reverse transcriptase: Evidence from in vitro and in vivo studies

Abstract

Ethnopharmacological relevance: Astragalus membranaceus is one of the most widely applied traditional Chinese herbal medicines. TA-65 is an extract of Astragalus membranaceus; however, the protective effects of TA-65 in brain damage during development remain unclear.

Aim of the study: To investigate the neuroprotective effects of TA-65 in a neonatal hypoxic-ischemic brain damage (HIBD) mouse model, focusing on the role of telomerase reverse transcriptase (TERT).

Materials and methods: In vivo and in vitro HIBD models were established and treated with TA-65. Nuclear and mitochondrial TERT expressions were measured by western blotting and immunofluorescence. Brain injury was evaluated through the measurement of brain infarction areas and neuronal apoptosis. The neurological function of mice was assessed. TA-65 safety was evaluated by measuring mouse body weight, random blood glucose level, blood cell count, liver and kidney function, and immune function, as well as detecting tumor occurrence in vital organs.

Results: TA-65 administration upregulated mitochondrial TERT expression after HIBD both in vivo and in vitro, but did not influence nuclear TERT expression. TA-65 reduced neuronal apoptosis and brain infarction areas, and improved neurological function in mice after HIBD. TA-65 did not change telomere length in the brain or affect body weight, random blood glucose levels, blood cell counts, liver and kidney function, or immune function in mice after HIBD. TA-65 administration did not cause tumor occurrence in the vital organs of mice.

Conclusions: TA-65 exerts neuroprotective effects in neonatal HIBD without significant side effects or tumorigenicity. The possible mechanism may involve enhanced mitochondrial TERT expression.

Keywords: Astragalus membranaceus; Hypoxic-ischemic brain damage; Safety; TA-65; Telomerase reverse transcriptase.