{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:46:09Z","timestamp":1764701169668,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Studies have demonstrated the therapeutic effects of Lindera plants. This study was undertaken to reveal the antihypertensive properties of Lindera erythrocarpa leaf ethanolic extract (LEL). Aorta segments of Sprague\u2013Dawley rats were used to study the vasodilatory effect of LEL, and the mechanisms involved were evaluated by treating specific inhibitors or activators that affect the contractility of blood vessels. Our results revealed that LEL promotes a vasorelaxant effect through the nitric oxide\/cyclic guanosine 3\u2032,5\u2032-monophosphate pathway, blocking the Ca2+ channels, opening the K+ channels, and inhibiting the vasoconstrictive action of angiotensin II. In addition, the effects of LEL on blood pressure were investigated in spontaneously hypertensive rats by the tail-cuff method. LEL (300 or 1000 mg\/kg) was orally administered to the rats, and 1000 mg\/kg of LEL significantly lowered the blood pressure. Systolic blood pressure decreased by \u221220.06 \u00b1 4.87%, and diastolic blood pressure also lowered by \u221230.58 \u00b1 5.92% at 4 h in the 1000 mg\/kg LEL group. Overall, our results suggest that LEL may be useful to treat hypertensive diseases, considering its vasorelaxing and hypotensive effects.<\/jats:p>","DOI":"10.3390\/nu16173003","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T08:36:08Z","timestamp":1725525368000},"page":"3003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antihypertensive Effects of Lindera erythrocarpa Makino via NO\/cGMP Pathway and Ca2+ and K+ Channels"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5583-473X","authenticated-orcid":false,"given":"Sujin","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5958-4944","authenticated-orcid":false,"given":"Junkyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0345-3000","authenticated-orcid":false,"given":"Ho-Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngmin","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8590-9480","authenticated-orcid":false,"given":"Kyungjin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s11892-019-1161-2","article-title":"Global Updates on Cardiovascular Disease Mortality Trends and Attribution of Traditional Risk Factors","volume":"19","author":"Jagannathan","year":"2019","journal-title":"Curr. Diabetes Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1161\/HYPERTENSIONAHA.119.14240","article-title":"High Blood Pressure and Cardiovascular Disease","volume":"75","author":"Fuchs","year":"2020","journal-title":"Hypertension"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1161\/HYPERTENSIONAHA.117.09026","article-title":"Prevalence, Correlates, and Prognosis of Healthy Vascular Aging in a Western Community-Dwelling Cohort: The Framingham Heart Study","volume":"70","author":"Niiranen","year":"2017","journal-title":"Hypertension"},{"unstructured":"NCD Risk Factor Collaboration (NCD-RisC) (2019). Long-term and recent trends in hypertension awareness, treatment, and control in 12 high-income countries: An analysis of 123 nationally representative surveys. Lancet, 394, 639\u2013651.","key":"ref_4"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/clc.23303","article-title":"Hypertension in older adults: Assessment, management, and challenges","volume":"43","author":"Oliveros","year":"2020","journal-title":"Clin. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1001\/jama.2020.14545","article-title":"Trends in Blood Pressure Control Among US Adults with Hypertension, 1999\u20132000 to 2017\u20132018","volume":"324","author":"Muntner","year":"2020","journal-title":"JAMA"},{"doi-asserted-by":"crossref","unstructured":"Alves-Silva, J.M., Zuzarte, M., Gir\u00e3o, H., and Salgueiro, L. (2022). Natural Products in Cardiovascular Diseases: The Potential of Plants from the Allioideae Subfamily (Ex-Alliaceae Family) and Their Sulphur-Containing Compounds. Plants, 11.","key":"ref_7","DOI":"10.3390\/plants11151920"},{"doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez, L., Mendez, D., Montecino, H., Carrasco, B., Arevalo, B., Palomo, I., and Fuentes, E. (2022). Role of Phaseolus vulgaris L. in the Prevention of Cardiovascular Diseases-Cardioprotective Potential of Bioactive Compounds. Plants, 11.","key":"ref_8","DOI":"10.3390\/plants11020186"},{"doi-asserted-by":"crossref","unstructured":"Samtiya, M., Aluko, R.E., Dhewa, T., and Moreno-Rojas, J.M. (2021). Potential Health Benefits of Plant Food-Derived Bioactive Components: An Overview. Foods, 10.","key":"ref_9","DOI":"10.3390\/foods10040839"},{"doi-asserted-by":"crossref","unstructured":"Souza, P.d., Silva, R.d.C.V.d., Mariano, L.N.B., Dick, S.L., Ventura, G.C., and Cechinel-Filho, V. (2023). Diuretic and Natriuretic Effects of Hesperidin, a Flavanone Glycoside, in Female and Male Hypertensive Rats. Plants, 12.","key":"ref_10","DOI":"10.3390\/plants12010025"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"601","DOI":"10.34172\/apb.2021.090","article-title":"Medicinal Plants in the Treatment of Hypertension: A Review","volume":"11","author":"Kamyab","year":"2021","journal-title":"Adv. Pharm. Bull."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.phymed.2015.10.012","article-title":"Traditional herbs: A remedy for cardiovascular disorders","volume":"23","author":"Rastogi","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1007\/s11101-015-9432-2","article-title":"The genus Lindera: A source of structurally diverse molecules having pharmacological significance","volume":"15","author":"Cao","year":"2016","journal-title":"Phytochem. Rev."},{"doi-asserted-by":"crossref","unstructured":"Ihm, S.-H., Park, S.-H., Lee, J.-O., Kim, O.-R., Park, E.-H., Kim, K.-R., Kim, J.-H., Hwang, B.-H., Youn, H.-J., and Oak, M.-H. (2021). A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice. Plants, 10.","key":"ref_14","DOI":"10.3390\/plants10112493"},{"doi-asserted-by":"crossref","unstructured":"Shin, S., Park, J., Choi, H.-Y., and Lee, K. (2023). Hypotensive and Endothelium-Dependent Vasorelaxant Effects of Grayblue Spicebush Ethanol Extract in Rats. Foods, 12.","key":"ref_15","DOI":"10.3390\/foods12234282"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00210-011-0643-9","article-title":"An ethanolic extract of Lindera obtusiloba stems causes NO-mediated endothelium-dependent relaxations in rat aortic rings and prevents angiotensin II-induced hypertension and endothelial dysfunction in rats","volume":"383","author":"Lee","year":"2011","journal-title":"N-S Arch. Pharmacol."},{"key":"ref_17","first-page":"1103","article-title":"Anti-Inflammatory Effect and Mechanism of Action of Lindera erythrocarpa Essential Oil in Lipopolysaccharide-Stimulated Raw264.7 Cells","volume":"16","author":"Ko","year":"2017","journal-title":"Excli J."},{"doi-asserted-by":"crossref","unstructured":"Yoon, C.-S., Lee, H., Liu, Z., Lee, H.-K., and Lee, D.-S. (2022). Effects of Compounds Isolated from Lindera erythrocarpa on Anti-Inflammatory and Anti-Neuroinflammatory Action in BV2 Microglia and RAW264.7 Macrophage. Int. J. Mol. Sci., 23.","key":"ref_18","DOI":"10.3390\/ijms23137122"},{"doi-asserted-by":"crossref","unstructured":"Jung, J., Shin, S., Park, J., Lee, K., and Choi, H.-Y. (2023). Hypotensive and Vasorelaxant Effects of Sanguisorbae Radix Ethanol Extract in Spontaneously Hypertensive and Sprague Dawley Rats. Nutrients, 15.","key":"ref_19","DOI":"10.3390\/nu15214510"},{"doi-asserted-by":"crossref","unstructured":"Shin, S., Park, J., Choi, H.-Y., Bu, Y., and Lee, K. (2024). Vasorelaxant and Hypotensive Effects of Galla chinensis in Rats. Int. J. Mol. Sci., 25.","key":"ref_20","DOI":"10.3390\/ijms25147962"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/micc.12040","article-title":"Diversity in Mechanisms of Endothelium-Dependent Vasodilation in Health and Disease","volume":"20","author":"Durand","year":"2013","journal-title":"Microcirculation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1089\/ars.2007.1959","article-title":"Nitric oxide in the vasculature: Where does it come from and where does it go? A quantitative perspective","volume":"10","author":"Chen","year":"2008","journal-title":"Antioxid. Redox Sign"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1253\/circj.CJ-10-0195","article-title":"Prostacyclin in Vascular Diseases\u2014Recent Insights and Future Perspectives","volume":"74","author":"Kawabe","year":"2010","journal-title":"Circ. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.lfs.2016.03.059","article-title":"Activation of PKA and Epac proteins by cyclic AMP depletes intracellular calcium stores and reduces calcium availability for vasoconstriction","volume":"155","year":"2016","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1093\/cvr\/cvy023","article-title":"Vascular smooth muscle contraction in hypertension","volume":"114","author":"Touyz","year":"2018","journal-title":"Cardiovasc. Res."},{"doi-asserted-by":"crossref","unstructured":"Hill-Eubanks, D.C., Werner, M.E., Heppner, T.J., and Nelson, M.T. (2011). Calcium Signaling in Smooth Muscle. Cold Spring Harb. Perspect. Biol., 3.","key":"ref_26","DOI":"10.1101\/cshperspect.a004549"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/j.1469-7793.2001.t01-1-00641.x","article-title":"The mechanism of phenylephrine-mediated [Ca2+]i oscillations underlying tonic contraction in the rabbit inferior vena cava","volume":"534","author":"Lee","year":"2001","journal-title":"J. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/bs.apha.2016.08.002","article-title":"Calcium Channels in Vascular Smooth Muscle","volume":"78","author":"Ghosh","year":"2017","journal-title":"Adv. Pharmacol."},{"doi-asserted-by":"crossref","unstructured":"Shah, K., Seeley, S., Schulz, C., Fisher, J., and Rao, S.G. (2022). Calcium Channels in the Heart: Disease States and Drugs. Cells, 11.","key":"ref_29","DOI":"10.3390\/cells11060943"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/bs.apha.2016.07.001","article-title":"Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth","volume":"78","author":"Jackson","year":"2017","journal-title":"Adv. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2147\/JRLCR.S36062","article-title":"K+ channels in biological processes: Vascular K+ channels in the regulation of blood pressure","volume":"7","author":"Werner","year":"2014","journal-title":"J. Receptor. Ligand Channel Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/fcp.12461","article-title":"Potassium channels in vascular smooth muscle: A pathophysiological and pharmacological perspective","volume":"33","author":"Dogan","year":"2019","journal-title":"Fund. Clin. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s11906-011-0187-x","article-title":"Cell Signaling of Angiotensin II on Vascular Tone: Novel Mechanisms","volume":"13","author":"Cat","year":"2011","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1152\/physiolgenomics.00065.2017","article-title":"Genetics of hypertension: An assessment of progress in the spontaneously hypertensive rat","volume":"49","author":"Doris","year":"2017","journal-title":"Physiol. Genom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0008-6363(98)00076-5","article-title":"Rat models of hypertension, cardiac hypertrophy and failure","volume":"39","author":"Doggrell","year":"1998","journal-title":"Cardiovasc. Res."},{"doi-asserted-by":"crossref","unstructured":"Tang, F., Yan, H.-L., Wang, L.-X., Xu, J.-F., Peng, C., Ao, H., and Tan, Y.-Z. (2021). Review of Natural Resources with Vasodilation: Traditional Medicinal Plants, Natural Products, and Their Mechanism and Clinical Efficacy. Front. Pharmacol., 12.","key":"ref_36","DOI":"10.3389\/fphar.2021.627458"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.lfs.2015.12.043","article-title":"Rat aorta as a pharmacological tool for in vitro and in vivo studies","volume":"145","author":"Rameshrad","year":"2016","journal-title":"Life Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11739-011-0548-0","article-title":"Structural abnormalities of small resistance arteries in essential hypertension","volume":"7","author":"Rizzoni","year":"2012","journal-title":"Intern. Emerg. Med."},{"doi-asserted-by":"crossref","unstructured":"Odukoya, J.O., Odukoya, J.O., Mmutlane, E.M., and Ndinteh, D.T. (2022). Ethnopharmacological Study of Medicinal Plants Used for the Treatment of Cardiovascular Diseases and Their Associated Risk Factors in sub-Saharan Africa. Plants, 11.","key":"ref_39","DOI":"10.3390\/plants11101387"},{"doi-asserted-by":"crossref","unstructured":"Uy, N.P., Kim, J.H., Kim, D.Y., Ku, J., and Lee, S. (2024). Analysis of Marker Compounds in Lindera erythrocarpa from Diverse Geographical Regions of Korea. Separations, 11.","key":"ref_40","DOI":"10.3390\/separations11080252"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/17\/3003\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:49:13Z","timestamp":1760111353000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/17\/3003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,5]]},"references-count":40,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["nu16173003"],"URL":"https:\/\/doi.org\/10.3390\/nu16173003","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2024,9,5]]}}}