{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:10:12Z","timestamp":1784182212297,"version":"3.55.0"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cardiovascular diseases (CVDs) are closely associated with mitochondrial dysfunction, including impaired mitochondrial biogenesis, abnormal mitochondrial dynamics, excessive oxidative stress, dysregulated mitophagy, and disorders of energy metabolism. Accumulating evidence indicates that natural products exert significant cardioprotective effects by coordinately regulating multiple mitochondrial pathways, thereby alleviating myocardial injury and slowing disease progression. This review systematically summarises recent advances in natural metabolites and their rational combination strategies for cardiovascular diseases, with a particular focus on mitochondrial regulation. Representative metabolites, including flavonoids, alkaloids, saponins, and polyphenols, regulate key signalling pathways such as SIRT1\/PGC-1\u03b1, AMPK, Nrf2, PINK1\/Parkin, and Drp1\/MFN2 to restore mitochondrial homeostasis. Importantly, natural metabolite combinations further demonstrate synergistic and complementary effects through coordinated regulation of distinct mitochondrial pathways. For example, EGCG and Rhein cooperatively alleviate myocardial ischemia\/reperfusion injury by simultaneously suppressing oxidative stress and TLR4-mediated inflammatory signalling. Collectively, this review highlights the considerable potential of natural products and their rational combinations as therapeutic strategies for cardiovascular diseases through the modulation of mitochondrial function.<\/jats:p>","DOI":"10.3389\/fphar.2026.1851598","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:39:24Z","timestamp":1784180364000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plant metabolites targeting mitochondrial dysfunction in cardiovascular diseases: pharmacological mechanisms and combination strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuyao","family":"Wang","sequence":"first","affiliation":[{"name":"Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisi","family":"He","sequence":"additional","affiliation":[{"name":"Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"Gao","sequence":"additional","affiliation":[{"name":"Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]},{"name":"Shandong Key Laboratory of Innovation and Application Research in Basic Theory of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]},{"name":"Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"254","DOI":"10.7555\/JBR.38.20240387","article-title":"Molecular pathways in cardiovascular disease under hypoxia: mechanisms, biomarkers, and therapeutic targets","volume":"39","author":"Abdullaev","year":"2025","journal-title":"J. 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