Cheng L.-C.Guo B.-C.Chen C.-H.Chang C.-J.Yeh T.-S.TZONG-SHYUAN LEE2020-06-302020-06-3020201661-6596https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079886194&doi=10.3390%2fijms21041532&partnerID=40&md5=ae1c785833214178c52da019ff40b435https://scholars.lib.ntu.edu.tw/handle/123456789/507366Torenia concolor Lindley var. formosama Yamazaki ethanolic extract (TCEE) is reported to have anti-inflammatory and anti-obesity properties. However, the effects of TCEE and its underlying mechanisms in the activation of endothelial nitric oxide synthase (eNOS) have not yet been investigated. Increasing the endothelium-derived nitric oxide (NO) production has been known to be beneficial against the development of cardiovascular diseases. In this study, we investigated the effect of TCEE on eNOS activation and NO-related endothelial function and inflammation by using an in vitro system. In endothelial cells (ECs), TCEE increased NO production in a concentration-dependent manner without affecting the expression of eNOS. In addition, TCEE increased the phosphorylation of eNOS at serine 635 residue (Ser635) and Ser1179, Akt at Ser473, calmodulin kinase II (CaMKII) at threonine residue 286 (Thr286), and AMP-activated protein kinase (AMPK) at Thr172. Moreover, TCEE-induced NO production, and EC proliferation, migration, and tube formation were diminished by pretreatment with LY294002 (an Akt inhibitor), KN62 (a CaMKII inhibitor), and compound C (an AMPK inhibitor). Additionally, TCEE attenuated the tumor necrosis factor-α-induced inflammatory response as evidenced by the expression of adhesion molecules in ECs and monocyte adhesion onto ECs. These inflammatory effects of TCEE were abolished by L-NG-nitroarginine methyl ester (an NOS inhibitor). Moreover, chronic treatment with TCEE attenuated hyperlipidemia, systemic and aortic inflammatory response, and the atherosclerotic lesions in apolipoprotein E-deficient mice. Collectively, our findings suggest that TCEE may confer protection from atherosclerosis by preventing endothelial dysfunction. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.Anti-inflammatory effect; Atherosclerosis; Endothelial nitric oxide synthase; Formosama Yamazak; Nitric oxide; Torenia concolor Lindley var[SDGs]SDG31 [n,o bis(5 isoquinolinesulfonyl) n methyltyrosyl] 4 phenylpiperazine; 2 morpholino 8 phenylchromone; calcium calmodulin dependent protein kinase II; cholesterol; endothelial nitric oxide synthase; high density lipoprotein cholesterol; hydroxymethylglutaryl coenzyme A reductase kinase; intercellular adhesion molecule 1; interleukin 1beta; interleukin 6; macrophage inflammatory protein 2; monocyte chemotactic protein 1; n(g) nitroarginine methyl ester; plant extract; Torenia concolor lindley var formosama yamazaki extract; triacylglycerol; tumor necrosis factor; unclassified drug; vascular cell adhesion molecule 1; alcohol; endothelial nitric oxide synthase; nitric acid; plant extract; angiogenesis assay; animal experiment; animal model; antiatherosclerotic activity; Article; atherosclerosis; atherosclerotic plaque; bioavailability; cell adhesion; cell adhesion assay; cell migration; cell migration assay; cell proliferation; cell proliferation assay; cell viability; cell viability assay; controlled study; drug activity; endothelium cell; enzyme linked immunosorbent assay; human; human cell; hyperlipidemia; inflammation; monocyte; mouse; MTT assay; nonhuman; protein expression; protein phosphorylation; Western blotting; atherosclerosis; cell line; cell motion; chemistry; drug effect; enzyme activation; enzymology; Lamiaceae; Lamiales; metabolism; pathology; pathophysiology; phosphorylation; THP-1 cell line; vascular endothelium; Atherosclerosis; Cell Line; Cell Movement; Cell Proliferation; Endothelial Cells; Endothelium, Vascular; Enzyme Activation; Ethanol; Humans; Lamiaceae; Lamiales; Nitric Acid; Nitric Oxide Synthase Type III; Phosphorylation; Plant Extracts; THP-1 Cellsjournal article10.3390/ijms21041532321023262-s2.0-85079886194