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Updated: May 8, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Panax notoginseng-derived extracellular vesicles alleviate doxorubicin-induced cardiotoxicity by suppressing p53
Mantang Jiang1, Tao Wang2, Guang Xin2
1Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Background:
Doxorubicin (Dox) is a highly effective chemotherapeutic agent, but its clinical use is limited by cumulative cardiotoxicity. Panax notoginseng, a traditional medicinal herb, exhibits well-documented cardioprotective properties; however, the therapeutic application of its bioactive constituents is constrained by poor bioavailability and potential toxicity. Plant-derived extracellular vesicles (EVs) have emerged as natural nanocarriers facilitating cross-kingdom delivery of bioactive metabolites. In this study, we investigated whether P. notoginseng-derived EVs (PEVs) could mitigate Dox-induced cardiotoxicity (DIC) and explored the underlying mechanisms.
Methods:
PEVs were isolated from P. notoginseng rhizomes and systematically characterized, with metabolite profiling performed by UPLC-MS. Cellular uptake, biodistribution, and cardioprotective effects were evaluated in Dox-injured cardiomyocytes and a chronic mouse model of DIC. Mechanistic insights were obtained using transcriptomic analysis, molecular docking, and biochemical assays.
Results:
PEVs were stable nanosized vesicles enriched with characteristic P. notoginseng metabolites, including triterpenoid saponins and dencichine. PEVs were efficiently internalized by cardiomyocytes and preferentially accumulated in injured myocardium. Functionally, PEVs attenuated Dox-induced inflammation, apoptosis, myocardial atrophy, fibrosis, and cardiac dysfunction, with efficacy comparable to dexrazoxane. Mechanistically, transcriptomic and molecular analysis identified p53 as a central regulatory target. PEVs-derived metabolites targeted the p53 DNA-binding domain, suppressing p53 phosphorylation and transcriptional activation of pro-apoptotic and inflammatory genes. Notably, p53 activation attenuated PEVs-mediated protection, whereas p53 inhibition or silencing abolished additional protective effects, indicating a p53-dependent mechanism.
Conclusion:
PEVs protect against DIC by delivering bioactive metabolites to injured myocardium and inhibiting p53-driven oxidative, inflammatory, and apoptotic pathways, highlighting their potential as a phytomedicine-based cardioprotective strategy.
