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Current literature has largely emphasized naringin, the glycosylated derivative of naringenin. However, as naringenin represents the physiologically active form, it is critical to consolidate and evaluate existing knowledge on its mechanisms of action, particularly in relation to cardiovascular disease (CVD). In this review, we examine the effects of naringenin on CVD and the major hub pathways underlying its pleiotropic effects. Naringenin demonstrates benefecial effects on multiple risk factors of CVD such as diabetes, dyslipidemia, ischemia, smoking and obesity through diverse signaling pathways. Notably, naringenin regulates the cyclic guanosine monophosphate (cGMP)\u2010protein kinase G (PKG) hub pathway, thereby influencing a spectrum of downstream cascades contributing to its therapeutic potential. Despite these promising findings, the major drawback in the effect of naringenin is its limited bioavailability. Naringenin occurs in glycosylated forms (naringin, narirutin, and naringenin\u2010glucoside) and as aglycones (naringenin) with both the forms exhibiting cardioprotective properties. However, with only limited number of clinical trials have investigated its efficacy in CVD, further clinical trials are essential to establish its naringenin's therapeutic value as a potential drug candidate.<\/jats:p>","DOI":"10.1002\/ardp.70287","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T12:27:56Z","timestamp":1783340876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Essential Pharmacokinetics and Pharmacodynamics of Naringenin: Underpinning the Cardioprotective Potential of Citrus\u2010Based Traditional Medicine"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4601-9933","authenticated-orcid":false,"given":"Shinn\u2010Zong","family":"Lin","sequence":"first","affiliation":[{"name":"Bioinnovation Center, Buddhist Tzu Chi Medical Foundation Hualien Taiwan"},{"name":"Department of Neurosurgery Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanmugavadivu","family":"Muthusamy","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Dr. NGP Arts and Science College Coimbatore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Reena","family":"Paul","sequence":"additional","affiliation":[{"name":"Cardiovascular and Mitochondria Related Diseases Research Center, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya K.","family":"Saju","sequence":"additional","affiliation":[{"name":"Regenerative Engineering and Molecular Medicine Laboratory, Department of Biotechnology Bharathiar University Coimbatore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Wen","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology College of Life Sciences, China Medical University Taichung Taiwan"},{"name":"School of Pharmacy, China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2347-0411","authenticated-orcid":false,"given":"Chih\u2010Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Cardiovascular and Mitochondria Related Diseases Research Center, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan"},{"name":"Division of Precesion Chinese Herbal Medicine and Molecular Medicine Research E\u2010Da Cancer Hospital, E\u2010Da Healthcare Group Kaohsiung Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital China Medical University Taichung Taiwan"},{"name":"Department of Biotechnology Asia University Taichung Taiwan"},{"name":"Graduate Institute of Biomedical Science China Medical University Taichung City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6381-3525","authenticated-orcid":false,"given":"Shibu","family":"Marthandam Asokan","sequence":"additional","affiliation":[{"name":"Regenerative Engineering and Molecular Medicine Laboratory, Department of Biotechnology Bharathiar University Coimbatore India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/2048004016687211"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.031855"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753944717692293"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/jns.2016.41"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.954555"},{"key":"e_1_2_15_7_1","first-page":"20","article-title":"Review on 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