{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T22:32:09Z","timestamp":1788215529249,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Unit \u2013 King Abdulaziz University \u2013 Kingdom of Saudi Arabia","award":["UE-41-115"],"award-info":[{"award-number":["UE-41-115"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Vasodilators are an important class in the management of hypertension and related cardiovascular disorders. In this regard, the chloroform fraction of Hypericum revolutum (HR) has been reported to produce vasodilating activity in phenylephrine-precontracted aortae. The current work aims to identify the active metabolites in the chloroform fraction of HR and illustrate the possible mechanism of action. The vasodilation activities were investigated using the isolated artery technique. NO vascular release was assessed by utilizing the NO-sensitive fluorescent probe DAF-FM. Free radical scavenging capacity was assessed utilizing DPPH. Chemical investigation of this fraction yielded two new compounds, revolutin (1) and hyperevolutin C (2), along with three known metabolites, ?-sitosterol (3), euxanthone (4), and 2,3,4-tirmethoxy xanthone (5). Compounds 1, 2, 3, and 5 showed significant vasodilation activities that were blocked by either endothelial denudation or L-NAME (nitric oxide synthase inhibitor), pointing towards a role of endothelial nitric oxide in their activities. In confirmation of this role, compounds 1\u20133 showed a significant release of NO from isolated vessels, as indicated by DAF-FM. On the other hand, only compound 5 showed free radical scavenging activities, as indicated by DPPH. In conclusion, isolated compounds 1, 2, 3, and 5 produce vasodilation activities that are dependent on endothelial nitric oxide release.<\/jats:p>","DOI":"10.3390\/biology10060541","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T04:15:46Z","timestamp":1623903346000},"page":"541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nitric-Oxide-Mediated Vasodilation of Bioactive Compounds Isolated from Hypericum revolutum in Rat Aorta"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0234-7492","authenticated-orcid":false,"given":"Hossam M.","family":"Abdallah","sequence":"first","affiliation":[{"name":"Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha Z.","family":"Timraz","sequence":"additional","affiliation":[{"name":"Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-7560","authenticated-orcid":false,"given":"Sabrin R. M.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Batterjee Medical College, North Obhur, Abdullah Al-Faisal Street, Jeddah 21442, Saudi Arabia"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali M.","family":"El-Halawany","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azizah M.","family":"Malebari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim A.","family":"Shehata","sequence":"additional","affiliation":[{"name":"Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6838-6945","authenticated-orcid":false,"given":"Hany M.","family":"El-Bassossy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S457","DOI":"10.1097\/00005344-198406002-00020","article-title":"Sodium balance and peripheral resistance in arterial hypertension","volume":"6","author":"Bianchi","year":"1984","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2143\/AC.55.4.2005744","article-title":"Endothelial dysfunction in hypertension","volume":"55","author":"Puddu","year":"2000","journal-title":"Acta Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.vph.2016.05.016","article-title":"Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?","volume":"86","author":"McCarthy","year":"2016","journal-title":"Vascul. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.jep.2019.02.024","article-title":"Medicinal plants with concomitant anti-diabetic and anti-hypertensive effects as potential sources of dual acting therapies against diabetes and hypertension: A review","volume":"235","author":"Chukwuma","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_5","first-page":"15","article-title":"Conservation of medicinal plants on the Arabian Peninsula","volume":"3","author":"Ahmad","year":"1991","journal-title":"J. Med. Plant Cons."},{"key":"ref_6","unstructured":"Collenette, S. (1999). Wildflowers of Saudi Arabia, National Commission for Wildlife Conservation and Development (NCWCD)."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9153","DOI":"10.5897\/AJB10.1570","article-title":"Pharmaceutically important plants used in traditional system of Arab medicine for the treatment of livestock ailments in the kingdom of Saudi Arabia","volume":"10","author":"Sher","year":"2011","journal-title":"Afr. J. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Miraldi, E., Biagi, M., and Giachetti, D. (2006). Chemical constituents and effect of topical application of Oleum hyperici on skin sensitivity to simulated sun exposure. Nat. Prod. Comm., 1.","DOI":"10.1177\/1934578X0600100307"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jep.2009.09.035","article-title":"Medicinal plants used by traditional medicine practitioners in the treatment of tuberculosis and related ailments in Uganda","volume":"127","author":"Tabuti","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","first-page":"132","article-title":"Plants used in traditional management of human ailments at Bale Mountains National Park, Southeastern Ethiopia","volume":"2","author":"Yineger","year":"2013","journal-title":"J. Med. Plants Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/hlca.19890720307","article-title":"New Hyperforin Derivatives from Hypericum revolutum Vahl with Growth-Inhibitory Activity Against a Human Colon Carcinoma Cell Line","volume":"72","author":"Decosterd","year":"1989","journal-title":"Helv. Chim. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1002\/hlca.19870700705","article-title":"New antifungal chromenyl ketones and their pentacyclic dimers from Hypericum revolutum Vahl","volume":"70","author":"Hostettmann","year":"1987","journal-title":"Helv. Chim. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1055\/s-2007-969238","article-title":"A new antifungal chromene and a related di-chromene from Hypericum revolutum","volume":"52","author":"Decosterd","year":"1986","journal-title":"Planta Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.4314\/tjpr.v20i5.17","article-title":"Vasodilating effect of Hypericum revolutum (Vahl) (Clusiaceae) methanol extract in rats","volume":"20","author":"Timraz","year":"2021","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1111\/j.1476-5381.2010.00872.x","article-title":"Animal research: Reporting In Vivo experiments: The ARRIVE guidelines","volume":"160","author":"Kilkenny","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_16","unstructured":"Underwood, W., and Anthony, R. (2020). AVMA Guidelines for the Euthanasia of Animals: 2020 Edition, American Veterinary Medical Association. Retrieved on March 2020."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.jdiacomp.2016.04.006","article-title":"Geraniol improves the impaired vascular reactivity in diabetes and metabolic syndrome through calcium channel blocking effect","volume":"30","author":"Elberry","year":"2016","journal-title":"J. Diabetes Complicat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1002\/ptr.4917","article-title":"Chrysin and luteolin attenuate diabetes-induced impairment in endothelial-dependent relaxation: Effect on lipid profile, AGEs and NO generation","volume":"27","author":"Fahmy","year":"2013","journal-title":"Phytother. Res."},{"key":"ref_19","first-page":"6019","article-title":"6-Gingerol alleviates exaggerated vasoconstriction in diabetic rat aorta through direct vasodilation and nitric oxide generation","volume":"9","author":"Ghareib","year":"2015","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tarkhan, M.M., Balamsh, K.S., and El-Bassossy, H.M. (2019). Cinnamaldehyde protects from methylglyoxal-induced vascular damage: Effect on nitric oxide and advanced glycation end products. J. Food Biochem., e12907.","DOI":"10.1111\/jfbc.12907"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1590\/S0103-50531997000500011","article-title":"Xanthones and other constituents of Vismia parviflora","volume":"8","author":"Nagem","year":"1997","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_22","first-page":"88","article-title":"Isolation and characterisation of stigmasterol and \u03b2-sitosterol from Odontonema strictum (Acanthaceae)","volume":"2","author":"Pierre","year":"2015","journal-title":"J. Innov. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1021\/np000215m","article-title":"New xanthones from Calophyllum caledonicum","volume":"63","author":"Morel","year":"2000","journal-title":"J. Nat. Prod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0031-9422(00)84276-4","article-title":"Neue phloroglucin-derivate aus Helichrysum natalitium und Helichrysum bellum","volume":"18","author":"Bohlmann","year":"1979","journal-title":"Phytochemistry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S0031-9422(99)00617-2","article-title":"Phloroglucinol derivatives from Hypericum japonicum","volume":"53","author":"Hu","year":"2000","journal-title":"Phytochemistry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1016\/0031-9422(92)83713-9","article-title":"Polyprenols and acylphloroglucinols from Esenbeckia nesiotica","volume":"31","author":"Rios","year":"1992","journal-title":"Phytochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1021\/np2003319","article-title":"Antibacterial acylphloroglucinols from Hypericum olympicum","volume":"75","author":"Shiu","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1021\/np300237n","article-title":"Bi-, Tri-, and Polycyclic Acylphloroglucinols from Hypericum empetrifolium","volume":"75","author":"Schmidt","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6327","DOI":"10.1016\/j.bmc.2015.08.028","article-title":"Isolation and anticancer, anthelminthic, and antiviral (HIV) activity of acylphloroglucinols, and regioselective synthesis of empetrifranzinans from Hypericum roeperianum","volume":"23","author":"Fobofou","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/S0031-9422(00)88736-1","article-title":"Neue phloroglucin-derivate aus Leontonyx-arten sowie weitere verbindungen aus vertretern der tribus inuleae","volume":"17","author":"Bohlmann","year":"1978","journal-title":"Phytochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1016\/S0031-9422(00)82740-5","article-title":"Weitere phloroglucin-derivate aus Helichrysum-arten","volume":"18","author":"Bohlmann","year":"1979","journal-title":"Phytochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.phytol.2015.03.001","article-title":"Aegyptolidines A and B: New pyrrolidine alkaloids from the fungus Aspergillus aegyptiacus","volume":"12","author":"Ibrahim","year":"2015","journal-title":"Phytochem. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3389\/fphar.2021.627458","article-title":"Review of Natural Resources With Vasodilation: Traditional Medicinal Plants, Natural Products, and Their Mechanism and Clinical Efficacy","volume":"12","author":"Tang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Azhar, A.S., El-Bassossy, H.M., and Abdallah, H.M. (2018). Mentha longifolia alleviates experimentally induced angina via decreasing cardiac load. J. Food Biochem., e12702.","DOI":"10.1111\/jfbc.12702"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12906-016-1340-5","article-title":"Phenolics from Garcinia mangostana alleviate exaggerated vasoconstriction in metabolic syndrome through direct vasodilatation and nitric oxide generation","volume":"16","author":"Abdallah","year":"2016","journal-title":"BMC Complement. Altern. Med."},{"key":"ref_36","first-page":"121","article-title":"Nitric oxide, vasodilation and the red blood cell","volume":"51","author":"Simmonds","year":"2014","journal-title":"Biorheology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.joim.2019.04.002","article-title":"Potential of phloroglucinol to improve erectile dysfunction associated with streptozotocin-induced diabetes in rats","volume":"17","author":"Kashif","year":"2019","journal-title":"J. Integr. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5520","DOI":"10.1002\/chem.200305209","article-title":"Terpenoids with a New Skeleton and Novel Triterpenoids with Anti-inflammatory Effects from Garcinia subelliptica","volume":"9","author":"Weng","year":"2003","journal-title":"Chem. Eur. J."},{"key":"ref_39","first-page":"157","article-title":"Ameliorative effects of \u03b2-sitosterol on some biochemical indices of hypertension in wistar albino rats","volume":"43","author":"Olaiya","year":"2014","journal-title":"Afr. J. Med. Med. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.phymed.2009.12.003","article-title":"Mechanism of the vasodilator effect of Euxanthone in rat small mesenteric arteries","volume":"17","author":"Lemos","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/S0968-0896(01)00315-7","article-title":"Antihypertensive and vasorelaxing activities of synthetic xanthone derivatives","volume":"10","author":"Wang","year":"2002","journal-title":"Bioorg. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1142\/S0192415X14500724","article-title":"Chrysin and luteolin alleviate vascular complications associated with insulin resistance mainly through PPAR-gamma activation","volume":"42","author":"Fahmy","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.cbi.2014.09.014","article-title":"Heme oxygenase-1 alleviates vascular complications associated with metabolic syndrome: Effect on endothelial dependent relaxation and NO production","volume":"223","author":"Hassan","year":"2014","journal-title":"Chem. Biol. Interact."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/6\/541\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:17:20Z","timestamp":1760163440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/6\/541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,17]]},"references-count":43,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["biology10060541"],"URL":"https:\/\/doi.org\/10.3390\/biology10060541","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,17]]}}}