Integrated Transcriptomic and Proteomic Analysis Elucidates the Mechanisms of Huperzine A Injection Against Cerebral Ischemia/Reperfusion Injury.

Authors

Yule Wang, Li Xie, Yue Gao

Published in

Drug design, development and therapy. Volume 20. Pages 627785. Epub Sep 09, 2026.

Abstract

After recanalization in acute ischemic stroke, cerebral ischemia/reperfusion injury (CI/RI) drives a cascade of pathophysiological events that worsen clinical outcomes, yet effective therapeutic options remain limited. Given the neuroprotective potential of Huperzine A (HupA), the efficacy of HupA injection (HAI, a major clinical formulation of HupA) against CI/RI and its underlying molecular basis warrant investigation.
In a mouse model of CI/RI, neurological performance, locomotor ability, cerebral infarction, histopathological alterations, and apoptotic neurons were jointly used to assess the anti-CI/RI effect of HAI at two different doses. An integrated transcriptomic and proteomic strategy was adopted to decipher the key anti-CI/RI mechanisms of HAI and then validated experimentally.
Compared with vehicle‑treated CI/RI mice, HAI intervention significantly alleviated neurobehavioral deficits, decreased infarct size, mitigated histopathological damage, and suppressed neuronal apoptosis (P < 0.01). Both separate and combined transcriptomic and proteomic analyses highlighted that the complement and coagulation cascades, together with inflammation, were strongly correlated with HAI's beneficial action in preventing CI/RI. Indeed, HAI treatment effectively normalized the dysregulated mRNA and protein levels of pivotal targets within the complement and coagulation cascades, including C3, C5, C9, CFB, MASP2, F7, F10, F12, and SERPINE1, in the damaged cortical tissues of CI/RI mice (P < 0.05). Moreover, this intervention markedly attenuated the abnormally elevated expression of multiple inflammatory mediators, including TLR2, TLR4, TNF-α, IL-1β, IL-6, CCL2, CCL5, CXCL1, ICAM1, S100A9, LCN2, MMP8, and MMP9, at both the mRNA and protein levels (P < 0.01).
Collectively, our data suggest that HAI may confer efficacy against CI/RI by modulating the complement and coagulation cascades and orchestrating the inflammatory response. Although further investigation is warranted, these preliminary findings provide a foundation for accelerating the clinical translation of HAI as a novel neuroprotectant against CI/RI in ischemic stroke.

PMID:
42733864
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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