Buyang Huanwu decoction promotes angiogenesis after cerebral ischemia through modulating caveolin-1-mediated exosome MALAT1/YAP1/HIF-1α axis

Bowei Chen; Yaqian Xu; Fengming Tian; Yingfei Liu; Jian Yi; Yin Ouyang; Fanzuo Zeng; Yanmei Peng; Baiyan Liu

doi:10.1016/j.phymed.2024.155609

Buyang Huanwu decoction promotes angiogenesis after cerebral ischemia through modulating caveolin-1-mediated exosome MALAT1/YAP1/HIF-1α axis

Phytomedicine. 2024 Apr 8:129:155609. doi: 10.1016/j.phymed.2024.155609. Online ahead of print.

Authors

Bowei Chen¹, Yaqian Xu¹, Fengming Tian¹, Yingfei Liu¹, Jian Yi², Yin Ouyang¹, Fanzuo Zeng¹, Yanmei Peng³, Baiyan Liu⁴

Affiliations

¹ The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
² The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China; Hunan Academy of Chinese Medicine, Changsha 410006, China.
³ Hunan Academy of Chinese Medicine, Changsha 410006, China.
⁴ Hunan Academy of Chinese Medicine, Changsha 410006, China. Electronic address: liubaiyan9657@163.com.

PMID: 38677273
DOI: 10.1016/j.phymed.2024.155609

Abstract

Background: Angiogenesis is an effective method for promoting neurological function recovery after cerebral ischemia (CI). Buyang Huanwu decoction (BHD) is a traditional Chinese medicinal recipe that is frequently employed for CI treatment. Previous investigations have validated that it promotes angiogenesis following CI. Nevertheless, the precise mechanism by which it does this has yet to be completely understood.

Objective: This study aims to examine the underlying mechanism through which BHD facilitates angiogenesis following CI by regulating the exosomal MALAT1/YAP1/HIF-1α signaling axis, specifically via the involvement of caveolin-1 (Cav1), an endocytosis-associated protein.

Methods: A CI model was created using middle cerebral artery occlusion (MCAO). Following the administration of multiple doses of BHD, various parameters, including the neurobehavioral score, pathological damage, and angiogenesis, were assessed in each group of mice to identify the optimal dosage of BHD for treating CI. The molecular processes underlying the angiogenic implications of BHD following CI were investigated exhaustively by employing single-cell sequencing. Finally, the involvement of Cav1 was confirmed in Cav1 knockout mice and Cav1-silenced stably transfected strains to validate the mechanism by which BHD increases angiogenesis following CI.

Results: BHD could promote angiogenesis after CI. Single-cell sequencing results suggested that its potential mechanism of action might be connected with Cav1 and the exosomal MALAT1/YAP1/HIF-1α signaling axis. BHD could promote angiogenesis after CI by regulating the exosomal MALAT1/YAP1/HIF-1α axis through Cav1, as validated in vivo and in vitro experiments. Accordingly, Cav1 may be a key target of BHD in promoting angiogenesis after CI.

Conclusion: This investigation represents the initial attempt to comprehensively ascertain the underlying mechanism of action of BHD in treating CI using single-cell sequencing, gene-knockout mice, and stable transfected cell lines, potentially associated with the modulation of the exosomal MALAT1/YAP1/HIF-1α axis by Cav1. Our findings offer novel empirical evidence for unraveling the regulatory pathways through which Cav1 participates in angiogenesis following CI and shed light on the potential mechanisms of BHD.

Keywords: Angiogenesis; Buyang Huanwu decoction; Caveolin 1; Cerebral ischemia; Exosomal MALAT1/YAP1/HIF-1α axis; Single-cell sequencing.