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In the diabetes state, presence of hyperglycemia and insulin resistance predisposes to endothelial dysfunction. <jats:italic>Clinacanthus nutans<\/jats:italic>, widely used as a traditional medicine for diabetes is reported to have hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory properties. However, the possibility of <jats:italic>C. nutans<\/jats:italic> affecting the vascular endothelial function in diabetes remains unclear. This study was aimed at evaluating the effects of <jats:italic>C. nutans<\/jats:italic> methanolic leaves extract (CNME) on endothelial function in a type 2 diabetes (T2DM) rat model. Sixty male Sprague-Dawley rats were divided into five groups (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>12<\/mml:mn><\/mml:math> per group): nondiabetic control, nondiabetic treated with four weeks of CNME (500\u2009mg\/kg\/daily), untreated diabetic rats, diabetic treated with metformin (300\u2009mg\/kg\/daily), and diabetic treated with CNME (500\u2009mg\/kg\/daily). T2DM was induced by a single intraperitoneal injection of low-dose streptozotocin (STZ) to rats fed with high-fat diet (HFD). Endothelial-dependent and endothelial-independent relaxations and contractions of the thoracic aorta were determined using the organ bath. Aortic endothelial nitric oxide synthase (eNOS) expression was determined using Western blotting. Endothelial-dependent relaxation was reduced in diabetic rats. Both diabetic groups treated with CNME or metformin significantly improved the impairment in endothelium-dependent vasorelaxation; this was associated with increased expression of aortic eNOS protein. CNME- and metformin-treated groups also reduced aortic endothelium-dependent and aortic endothelium-independent contractions in diabetics. Both of these diabetic-treated groups also reduced blood glucose levels and increased body weight compared to the untreated diabetic group. In conclusion, <jats:italic>C. nutans<\/jats:italic> improves endothelial-dependent vasodilatation and reduces endothelial-dependent contraction, thus ameliorating endothelial dysfunction in diabetic rats. This may occur due to its effect on increasing eNOS protein expression.<\/jats:p>","DOI":"10.1155\/2020\/7572892","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:06:26Z","timestamp":1597709186000},"page":"1-10","source":"Crossref","is-referenced-by-count":23,"title":["<i>Clinacanthus nutans<\/i> Leaves Extract Reverts Endothelial Dysfunction in Type 2 Diabetes Rats by Improving Protein Expression of eNOS"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1632-9754","authenticated-orcid":true,"given":"Ahmad Khusairi","family":"Azemi","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti Safiah","family":"Mokhtar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-953X","authenticated-orcid":true,"given":"Aida Hanum Ghulam","family":"Rasool","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia"},{"name":"Hospital Universiti Sains Malaysia, Kubang Kerian, 16150 Kota Bharu, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-010-9134-4"},{"key":"2","first-page":"7","volume":"14","year":"2013","journal-title":"International Journal of Integrative 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