Combined treatment with tPA and Chinese herbal medicine for ischemic stroke: is it valuable?

Tissue plasminogen activator (tPA) remains the only drug approved for acute ischemic stroke (AIS). However, its clinical application is limited by a narrow therapeutic window, hemorrhagic transformation (HT), and neurotoxicity. Recently, considerable progress has been made in exploring the protective mechanisms of Chinese herbal medicines (CHMs) against AIS, and several of these agents have been reported to improve the therapeutic efficacy of tPA.

This review explores the underlying mechanisms of adverse effects induced by tPA and summarizes the CHMs that have been demonstrated to mitigate these outcomes, with the aim of providing insights for the development of additional CHMs as adjuvants to tPA.

In accordance with the PRISMA guidelines, a comprehensive literature search was conducted across 6 scientific databases (PubMed, CNKI, Wanfang, CQVIP, Embase, and Cochrane Library) to identify studies published between January 2000 and November 2025, focusing on tPA thrombolysis, combined tPA and CHMs, and the application of CHMs in ischemic stroke.

Preclinical studies have identified 17 types of CHMs that alleviate the adverse effects of tPA-mediated thrombolysis by inhibiting inflammation, oxidative stress, matrix metalloproteinase (MMP) activation, blood-brain barrier (BBB) injury, or cell death. Among these, 13 types of CHMs exert a protective effect on the BBB. Furthermore, 21 types of CHMs have shown clinical efficacy in improving outcomes of tPA treatment. Notably, Danhong injection (DHI), Butylphthalide, Ginkgo Biloba extract and Shuxuening injection exhibit substantial potential for clinical application. Specifically, DHI has demonstrated consistent benefits in both preclinical and clinical settings, whereas Butylphthalide, Ginkgo Biloba extract and Shuxuening injection have demonstrated clinical efficacy across multiple independent trials. However, similar to other CHMs, these agents remain limited by insufficient investigation of their underlying mechanisms of action.

CHMs hold considerable potential as ancillary treatments for tPA, due to their unique advantage of multiple therapeutic effects. Future research should prioritize clinical validation to facilitate the integration of CHMs into modern therapeutic regimens as adjuvants to tPA.