{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:35:57Z","timestamp":1786700157025,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: The specific mechanisms underlying the antihypertensive actions of corosolic acid (CA) have not been systematically elucidated. Methods: Evidence was categorized according to major signaling and physiological pathways, including the renin\u2013angiotensin system (RAS), oxidative and inflammatory responses, endothelial and smooth muscle regulation (NO\/cGMP and H2S\/KATP), and kinase-mediated signaling (AMPK, NF-\u03baB, JAK\/STAT, PKC). Results: Consistent with in vitro and animal studies, CA has been reported to attenuate pro-hypertensive signaling through multiple pathways: (i) downregulating renin\u2013angiotensin system-related cascades; (ii) reduction in reactive oxygen species and inflammatory mediators through activation of AMPK and inhibition of NF-\u03baB and JAK\/STAT pathways; (iii) improved vascular tone by enhancing NO\/cGMP signaling, partly involving the H2S\/KATP pathway, and inhibiting PKC. CA may indirectly contribute to blood pressure reduction by improving glucose and lipid metabolism and adipose tissue inflammation, thereby affecting metabolic risk factors. The existing evidence gaps include: lack of direct studies on voltage-gated, receptor-gated and store-regulated calcium channels; the specific effects on the isoforms of nitric oxide synthase (eNOS\/iNOS\/nNOS) and PKC are not known; limited human data on the antihypertensive efficacy, dose effect and safety of CA in humans are available. Conclusions: CA may have multi-targeted blood-pressure-lowering potential. Its clinical efficacy and safety require further confirmation.<\/jats:p>","DOI":"10.3390\/molecules31162841","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:04:01Z","timestamp":1786698241000},"page":"2841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Insights into the Antihypertensive and Cardioprotective Actions of Corosolic Acid: A Narrative Review"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3134-6779","authenticated-orcid":false,"given":"Fangying","family":"Chen","sequence":"first","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Gelugor 11800 USM, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7259-4010","authenticated-orcid":false,"given":"Wan Yin","family":"Tew","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800 USM, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6639-9718","authenticated-orcid":false,"given":"Ming Thong","family":"Ong","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Gelugor 11800 USM, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4138-711X","authenticated-orcid":false,"given":"Mun Fei","family":"Yam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800 USM, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e103779","DOI":"10.1136\/bmjopen-2025-103779","article-title":"Prevalence, incidence and risk factors of chronic kidney disease in people with diabetes and hypertension, and the prognosis and kidney function decline in Indonesia: A multicentre cross-sectional study in primary care centres","volume":"15","author":"Hustrini","year":"2025","journal-title":"BMJ Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/ajh\/hpae050","article-title":"Effect of a Hypertensive Response During Exercise on Growth Rates of Aortic Diameters","volume":"37","author":"Rossi","year":"2024","journal-title":"Am. 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