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It is characterized by persistent elevation of BP levels, typically exceeding 140\/90\u2009mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L\u2010NG\u2010nitro arginine methyl ester (L\u2010NAME), an analog of L\u2010arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L\u2010NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L\u2010NAME\u2010induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L\u2010NAME\u2010induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin\u2010converting enzyme (ACE) and endothelin\u20101. Moreover, they exhibit anti\u2010inflammatory effects, attenuating inflammation\u2010mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L\u2010NAME\u2010induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management.<\/jats:p>","DOI":"10.1002\/ptr.8199","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T05:01:24Z","timestamp":1713157284000},"page":"3146-3168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Current insights and future perspectives of flavonoids: A promising antihypertensive approach"],"prefix":"10.1002","volume":"38","author":[{"given":"Urip","family":"Harahap","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Universitas Sumatera Utara  Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2016-0151","authenticated-orcid":false,"given":"Rony Abdi","family":"Syahputra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Universitas Sumatera Utara  Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Biotechnology and Environment University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azhari","family":"Nasution","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Universitas Sumatera Utara  Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenny","family":"Wisely","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Universitas Sumatera Utara  Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen Lazurit","family":"Sirait","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Universitas Sumatera Utara  Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aminah","family":"Dalimunthe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Universitas Sumatera Utara  Medan Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satirah","family":"Zainalabidin","sequence":"additional","affiliation":[{"name":"Biomedical Science, Centre of Toxicology and Health Risk Study, Faculty of Health Sciences Universiti Kebangsaan Malaysia  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurpudji Astuti","family":"Taslim","sequence":"additional","affiliation":[{"name":"Division of Clinical Nutrition, Department of Nutrition, Faculty of Medicine Hasanuddin University  Makassar Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2151-0854","authenticated-orcid":false,"given":"Fahrul","family":"Nurkolis","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga)  Yogyakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8678-156X","authenticated-orcid":false,"given":"Bonglee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"},{"name":"Korean Medicine\u2010Based Drug Repositioning Cancer Research Center, College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,14]]},"reference":[{"issue":"3","key":"e_1_2_14_2_1","first-page":"5","article-title":"Antihypertensive effects of roselle\u2010olive combination in L\u2010NAME\u2010induced hypertensive rats","volume":"2017","author":"Abdel\u2010Rahman R. 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