ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1594283
This article is part of the Research TopicPharmacology of Natural Products against Neurodegenerative DisordersView all 9 articles
Tetramethylpyrazine Enhances Neuroprotection and Plasticity in Cerebral Ischemia-Reperfusion Injury via RhoA/ROCK2 Pathway Inhibition
Provisionally accepted
- Zhongnan Hospital, Wuhan University, Wuhan, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Tetramethylpyrazine (TMP) is an active component of the Chuanxiong, effectively crosses blood-brain barrier (BBB). It exhibits neuroprotective potential in cerebral ischemia-reperfusion injury (CIRI). This study performed middle cerebral artery occlusion/reperfusion (MCAO/R) surgery in rats to evaluate TMP's efficacy and mechanisms in mitigating CIRI. Rats received intraperitoneal TMP (40 mg/kg) for three days prior to MCAO/R and continued for 14 days post-surgery. Behavioral tests were conducted using mNSS and Morris water maze tests. Histopathological analyses, including HE, Nissl, and TUNEL staining. mRNA sequencing revealed that RhoA and ROCK was upregulated in the CIRI model and downregulated by TMP treatment. GO enrichment and KEGG enrichment showed RhoA and ROCK were related to neuroplasticity. Western blot and immunofluorescence staining confirmed that TMP inhibited RhoA, ROCK2, phosphorylated LIMK, and phosphorylated cofilin expression. Additionally, TMP increased the levels of neuroplasticity-related proteins PSD95 and MAP2, promoting synaptic and dendritic regeneration. Administration of lysophosphatidic acid (LPA), a RhoA/ROCK pathway agonist, attenuated TMP's neuroprotective effects, validating the pathway's role in TMP-mediated protection. These findings indicate that TMP confers neuroprotection in CIRI by inhibiting the RhoA/ROCK pathway and enhancing neuroplasticity, underscoring its therapeutic potential in CIRI.
Keywords: Tetramethylpyrazine, Cerebral ischemia-reperfusion injury, neuroplasticity, Neuroprotection, nature products
Received: 15 Mar 2025; Accepted: 22 Apr 2025.
Copyright: © 2025 Zhang, Zhang, Shi, Liao and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Weijing Liao, Zhongnan Hospital, Wuhan University, Wuhan, China
Junbin Lin, Zhongnan Hospital, Wuhan University, Wuhan, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.