Administration of Huperzine A microspheres ameliorates myocardial ischemic injury via α7nAChR-dependent JAK2/STAT3 signaling pathway

Acetylcholinesterase (AChE) inhibitor (AChEI) is well established as first-line agents for relieving the symptoms of Alzheimer's disease (AD). Injectable sustained-release formulation of AChEI may be suitable for treating AD patients. However, it needs to know whether continuous inhibition of AChE could deteriorate or attenuate myocardial damage if myocardial ischemia (MI) occurs. Huperzine A microspheres (HAM) are a sustained-release formulation releasing sustainably huperzine A (an AChEI) for more than 7 days after a single dose of HAM. This study aimed to investigate the myocardial damage in an isoprenaline (ISO)-induced MI mice model during HAM treatment. The heart injury was evaluated by assaying serum CK-MB, Tn-I and observing histopathological changes. The levels of proinflammatory cytokines in serum were detected. The level of p-P65 and the expression of proteins in the JAK2/STAT3 signaling pathway were assayed with Western blot. Administration with a single dose of HAM resulted in inhibiting the MI-induced increases of CK-MB and Tn-I, alleviating the damage of heart tissue, and decreasing the levels of TNF-alpha and IL-6. In addition, HAM decreased the levels of p-P65, p-JAK2, and p-STAT3 in heart tissue. The effects of HAM could be weakened or abolished by the specific alpha 7nAChR antagonist. These findings suggest that continuous AChE inhibition could protect the heart from ischemic damage during administration of sustained-release formulation of AChEI, which is associated with the anti-inflammatory effect of HAM by regulating alpha 7nAChR-dependent JAK2/STAT3 signaling pathway.

Automated summary

This study aimed to investigate the myocardial damage in an isoprenaline (ISO)-induced MI mice model during Huperzine A microspheres (HAM) treatment. The results showed that continuous acetylcholinesterase (AChE) inhibition could protect the heart from ischemic damage and HAM exhibited anti-inflammatory effects through regulating the α7nAChR-dependent JAK2/STAT3 signaling pathway.