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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1431692

Combining systems pharmacology, metabolomics, and transcriptomics to reveal the mechanism of Salvia miltiorrhiza-Cortex moutan herb pair for the treatment of ischemic stroke

Provisionally accepted
Chao Zhao Chao Zhao 1Xiaodan Bai Xiaodan Bai 2Yi Ding Yi Ding 3Aidong Wen Aidong Wen 3Qiang Fu Qiang Fu 1*
  • 1 Department of Pharmaceutical Analysis, School of Pharmacy, Xi’an Jiaotong University, Xi'an, Shaanxi, China
  • 2 Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Air Force Medical University, Xi’an, China
  • 3 Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China

The final, formatted version of the article will be published soon.

    Ischemic stroke (IS), predominantly triggered by blockages in cerebral blood flow, is increasingly recognized as a critical public health issue. The combination of Salvia miltiorrhiza (SM) and Cortex moutan (CM), traditional herbs in Eastern medicine, are frequently used for managing heart and brain vascular conditions. However, the exact mechanisms by which this herb pair (SC) combats IS remain largely unexplored. This investigation focuses on pinpointing the active constituents in SC that contribute to its protective role and deciphering the mechanisms countering cerebral ischemia, particularly in a middle cerebral artery occlusion (MCAO) rat model. We employed UPLC-Q-TOF-MS/MS alongside network pharmacology for predicting SC's target actions against IS. Key ingredients were examined for their interaction with principal targets using molecular docking. The therapeutic impact was gauged through H&E, TUNEL, and Nissl staining, complemented by transcriptomic and metabolomic integration for mechanistic insights, with vital genes confirmed via western blot. UPLC-Q-TOF-MS/MS analysis revealed that the main components of SC included benzoylpaeoniflorin, salvianolic acid B, oxypaeoniflora, salvianolic acid A, and others. Network pharmacology analysis indicated that SC's mechanism in treating IS primarily involves inflammation, angiogenesis, and cell apoptosis-related pathways, potentially through targets such as AKT1, TNF, PTGS2, MMP9, PIK3CA, and VEGFA. Molecular docking underscored strong affinities between these constituents and their targets. Our empirical studies indicated SC's significant role in enhancing neuroprotection in IS, with transcriptomics suggesting the involvement of the VEGFA/PI3K/AKT pathway and metabolomics revealing improvements in various metabolic processes, including amino acids, glycerophospholipids, sphingomyelin, and fatty acids metabolisms.

    Keywords: Salvia miltiorrhiza, cortex moutan, ischemic stroke, Transcriptomics, Metabolomics, VEGFA/PI3K/AKT Pathway

    Received: 12 May 2024; Accepted: 27 Aug 2024.

    Copyright: © 2024 Zhao, Bai, Ding, Wen and Fu. 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: Qiang Fu, Department of Pharmaceutical Analysis, School of Pharmacy, Xi’an Jiaotong University, Xi'an, 710061, Shaanxi, 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.