Exploring the anti‑oxidative mechanisms of <em>Rhodiola rosea</em> in ameliorating myocardial fibrosis through network pharmacology and <em>in vitro</em> experiments

Zhang,Luna; Yin,Hang; Xie,Yumin; Zhang,Yueyue; Dong,Feihong; Wu,Ke; Yang,Le; Lv,Huiyi

doi:10.3892/mmr.2024.13338

Exploring the anti‑oxidative mechanisms of Rhodiola rosea in ameliorating myocardial fibrosis through network pharmacology and in vitro experiments

Authors:
- Luna Zhang
- Hang Yin
- Yumin Xie
- Yueyue Zhang
- Feihong Dong
- Ke Wu
- Le Yang
- Huiyi Lv
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Affiliations: Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA
Published online on: September 24, 2024 https://doi.org/10.3892/mmr.2024.13338
Article Number: 214
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial fibrosis (MF) significantly compromises cardiovascular health by affecting cardiac function through excessive collagen deposition. This impairs myocardial contraction and relaxation and leads to severe complications and increased mortality. The present study employed network pharmacology and in vitro assays to investigate the bioactive compounds of Rhodiola rosea and their targets. Using databases such as HERB, the Encyclopedia of Traditional Chinese Medicine, Pubchem, OMIM and GeneCards, the present study identified effective components and MF‑related targets. Network analysis was conducted with Cytoscape to develop a Drug‑Ingredient‑Target‑Disease network and the STRING database was utilized to construct a protein‑protein interaction network. Key nodes were analyzed for pathway enrichment using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Molecular interactions were further explored through molecular docking techniques. The bioactivity of salidroside (SAL), the principal component of Rhodiola rosea, against MF was experimentally validated in H9c2 cardiomyocytes treated with angiotensin II and assessed for cell viability, protein expression and oxidative stress markers. Network pharmacology identified 25 active ingredients and 372 targets in Rhodiola rosea, linking SAL with pathways such as MAPK, EGFR, advanced glycosylation end products‑advanced glycosylation end products receptor and Forkhead box O. SAL showed significant interactions with core targets such as albumin, IL6, AKT serine/threonine kinase 1, MMP9 and caspase‑3. In vitro, SAL mitigated AngII‑induced increases in collagen I and alpha smooth muscle actin protein levels and oxidative stress markers, demonstrating dose‑dependent effectiveness in reversing MF. SAL from Rhodiola rosea exhibited potent anti‑oxidative properties that mitigated MF by modulating multiple molecular targets and signaling pathways. The present study underscored the therapeutic potential of SAL in treating oxidative stress‑related cardiovascular diseases.

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