{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:02:23Z","timestamp":1760238143265,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T00:00:00Z","timestamp":1594339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1D1A1B07041820","2019R1F1A1061771"],"award-info":[{"award-number":["2018R1D1A1B07041820","2019R1F1A1061771"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Phellinus linteus is a well-known medicinal mushroom that is widely used in Asian countries. In several experimental models, Phellinus linteus extracts were reported to have various biological effects, including anti-inflammatory, anti-cancer, hepatoprotective, anti-diabetic, neuroprotective, and anti-angiogenic activity. In the present study, several bioactive compounds, including palmitic acid ethyl ester and linoleic acid, were identified in Phellinus linteus. The intermediate-conductance calcium-activated potassium channel (IKCa) plays an important role in the regulation of the vascular smooth muscle cells\u2019 (VSMCs) contraction and relaxation. The activation of the IKCa channel causes the hyperpolarization and relaxation of VSMCs. To examine whether Phellinus linteus extract causes vasodilation in the mesenteric arteries of rats, we measured the isometric tension using a wire myograph. After the arteries were pre-contracted with U46619 (a thromboxane analogue, 1 \u00b5M), Phellinus linteus extract was administered. The Phellinus linteus extract induced vasodilation in a dose-dependent manner, which was independent of the endothelium. To further investigate the mechanism, we used the non-selective K+ channel blocker tetraethylammonium (TEA). TEA significantly abolished Phellinus linteus extract-induced vasodilation. Thus, we tested three different types of K+ channel blockers: iberiotoxin (BKca channel blocker), apamin (SKca channel blocker), and charybdotoxin (IKca channel blocker). Charybdotoxin significantly inhibited Phellinus linteus extract-induced relaxation, while there was no effect from apamin and iberiotoxin. Membrane potential was measured using the voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)-trimethine oxonol (DiBAC4(3)) in the primary isolated vascular smooth muscle cells (VSMCs). We found that the Phellinus linteus extract induced hyperpolarization of VSMCs, which is associated with a reduced phosphorylation level of 20 KDa myosin light chain (MLC20).<\/jats:p>","DOI":"10.3390\/molecules25143160","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T09:45:31Z","timestamp":1594374331000},"page":"3160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Vasodilatory Effect of Phellinus linteus Extract in Rat Mesenteric Arteries"],"prefix":"10.3390","volume":"25","author":[{"given":"Youngin","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Medicine, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University, 50 Yeonseiro, Seodaemun-gu, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chae Eun","family":"Haam","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University, 50 Yeonseiro, Seodaemun-gu, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seonhee","family":"Byeon","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University, 50 Yeonseiro, Seodaemun-gu, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Jung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Food and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Hoon","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Food and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7115-6358","authenticated-orcid":false,"given":"Soo-Kyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University, 50 Yeonseiro, Seodaemun-gu, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University, 50 Yeonseiro, Seodaemun-gu, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/cphy.c160011","article-title":"Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles","volume":"7","author":"Tykocki","year":"2017","journal-title":"Compr. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jaminon, A., Reesink, K.D., A Kroon, A., and Schurgers, L.J. (2019). The Role of Vascular Smooth Muscle Cells in Arterial Remodeling: Focus on Calcification-Related Processes. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225694"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1111\/j.1440-1681.1996.tb01172.x","article-title":"POTASSIUM CHANNELS IN VASCULAR SMOOTH MUSCLE","volume":"23","author":"Brayden","year":"1996","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1152\/physiol.00040.2005","article-title":"Calcium-Activated Potassium Channels and the Regulation of Vascular Tone","volume":"21","author":"LeDoux","year":"2006","journal-title":"Physiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.fitote.2016.06.009","article-title":"Traditional uses, fermentation, phytochemistry and pharmacology of Phellinus linteus: A review","volume":"113","author":"Chen","year":"2016","journal-title":"Fitoterapia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.carbpol.2018.08.021","article-title":"Polysaccharide isolated from Phellinus linteus mycelia exerts anti-inflammatory effects via MAPK and PPAR signaling pathways","volume":"200","author":"Hu","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jep.2007.05.032","article-title":"The anti-inflammatory activity of Phellinus linteus (Berk. & M.A. Curt.) is mediated through the PKC\u03b4\/Nrf2\/ARE signaling to up-regulation of heme oxygenase-1","volume":"113","author":"Kim","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.carbpol.2015.02.009","article-title":"A novel polysaccharide from mycelia of cultured Phellinus linteus displays antitumor activity through apoptosis","volume":"124","author":"Mei","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"23565","DOI":"10.1038\/srep23565","article-title":"A proteomic analysis of mushroom polysaccharide-treated HepG2 cells","volume":"6","author":"Chai","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1749-8546-7-23","article-title":"Protective effect of Phellinus linteus polysaccharide extracts against thioacetamide-induced liver fibrosis in rats: A proteomics analysis","volume":"7","author":"Wang","year":"2012","journal-title":"Chin. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Huang, S.C., Wang, P.W., Kuo, P.C., Hung, H.Y., and Pan, T.L. (2018). Hepatoprotective Principles and Other Chemical Constituents from the Mycelium of Phellinus linteus. Molecules, 23.","DOI":"10.3390\/molecules23071705"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.intimp.2009.09.024","article-title":"Evaluation of antidiabetic activity of polysaccharide isolated from Phellinus linteus in non-obese diabetic mouse","volume":"10","author":"Kim","year":"2010","journal-title":"Int. Immunopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5456","DOI":"10.3390\/molecules20045456","article-title":"Cytoprotective Effect of Hispidin against Palmitate-Induced Lipotoxicity in C2C12 Myotubes","volume":"20","author":"Park","year":"2015","journal-title":"Molecules"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.nutres.2015.11.005","article-title":"Neuroprotective effects of the Phellinus linteus ethyl acetate extract against H2O2-induced apoptotic cell death of SK-N-MC cells","volume":"36","author":"Choi","year":"2016","journal-title":"Nutr. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1749-8546-8-25","article-title":"Phellinus linteus polysaccharide extracts increase the mitochondrial membrane potential and cause apoptotic death of THP-1 monocytes","volume":"8","author":"Verhoeven","year":"2013","journal-title":"Chin. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jep.2010.05.064","article-title":"Anti-angiogenic activity of methanol extract of Phellinus linteus and its fractions","volume":"131","author":"Lee","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0378-8741(03)00178-8","article-title":"Anti-angiogenic, antioxidant and xanthine oxidase inhibition activities of the mushroom Phellinus linteus","volume":"88","author":"Song","year":"2003","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1023\/A:1021935922722","article-title":"Inhibition of cytochrome P450 isozymes in rat liver microsomes by polysaccharides derived from Phellinus linteus","volume":"25","author":"Shon","year":"2003","journal-title":"Biotechnol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1007\/s12010-015-1896-4","article-title":"Endogenous and Exogenous Calcium Involved in the Betulin Production from Submerged Culture of Phellinus linteus Induced by Hydrogen Sulfide","volume":"178","author":"Fan","year":"2015","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_20","first-page":"381","article-title":"A case of the hepatocellular carcinoma during the pregnancy and metastasis to the left atrium","volume":"11","author":"Nam","year":"2005","journal-title":"Korean J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Liu, Y., Wang, C., Li, J., Mei, Y., and Liang, Y. (2019). Hypoglycemic and Hypolipidemic Effects of Phellinus Linteus Mycelial Extract from Solid-State Culture in A Rat Model of Type 2 Diabetes. Nutrients, 11.","DOI":"10.3390\/nu11020296"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1161\/01.HYP.31.2.615","article-title":"Linoleic acid induces relaxation and hyperpolarization of the pig coronary artery","volume":"31","author":"Pomposiello","year":"1998","journal-title":"Hypertension"},{"key":"ref_23","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":"2016","journal-title":"Adv. Pharmacol."},{"key":"ref_24","first-page":"e146","article-title":"Ion Channels and Vascular Diseases","volume":"39","author":"Cheng","year":"2019","journal-title":"Arter. Thromb. Vasc. Boil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fnmol.2018.00258","article-title":"Physiological Roles and Therapeutic Potential of Ca2+ Activated Potassium Channels in the Nervous System","volume":"11","author":"Kshatri","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15843","DOI":"10.1074\/jbc.M112.427187","article-title":"The Intermediate Conductance Calcium-activated Potassium Channel KCa3.1 Regulates Vascular Smooth Muscle Cell Proliferation via Controlling Calcium-dependent Signaling","volume":"288","author":"Bi","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1111\/j.1476-5381.2010.00803.x","article-title":"Openers of small conductance calcium-activated potassium channels selectively enhance NO-mediated bradykinin vasodilatation in porcine retinal arterioles","volume":"160","author":"Dalsgaard","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1085\/jgp.90.1.27","article-title":"Charybdotoxin selectively blocks small Ca-activated K channels in Aplysia neurons","volume":"90","author":"Hermann","year":"1987","journal-title":"J. Gen. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.bbrc.2015.09.073","article-title":"Pharmacology of hSlo3 channels and their contribution in the capacitation-associated hyperpolarization of human sperm","volume":"466","author":"Darszon","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"32723","DOI":"10.1074\/jbc.272.52.32723","article-title":"A Novel Gene, hKCa4, Encodes the Calcium-activated Potassium Channel in Human T Lymphocytes","volume":"272","author":"Logsdon","year":"1997","journal-title":"J. Boil. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1111\/j.1476-5381.1988.tb11772.x","article-title":"Effects of charybdotoxin, a blocker of Ca2+ -activated K + channels, on motor nerve terminals","volume":"95","author":"Anderson","year":"1988","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1159\/000107548","article-title":"Physical Integrity of Smooth Muscle Myosin Filaments is Enhanced by Phosphorylation of the Regulatory Myosin Light Chain","volume":"20","author":"Ip","year":"2007","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/cm.20471","article-title":"MLCK-independent phosphorylation of MLC20 and its regulation by MAP kinase pathway in human bladder smooth muscle cells","volume":"68","author":"Deng","year":"2010","journal-title":"Cytoskeleton"},{"key":"ref_34","first-page":"e58064","article-title":"Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography","volume":"20","author":"Sun","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Choi, S.-K., Kwon, Y., Byeon, S., Haam, C.E., and Lee, Y.-H. (2020). AdipoRon, adiponectin receptor agonist, improves vascular function in the mesenteric arteries of type 2 diabetic mice. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0230227"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1093\/cvr\/cvp054","article-title":"Comparison of contractile mechanisms of sphingosylphosphorylcholine and sphingosine-1-phosphate in rabbit coronary artery","volume":"82","author":"Choi","year":"2008","journal-title":"Cardiovasc. Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/14\/3160\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:49:54Z","timestamp":1760176194000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/14\/3160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,10]]},"references-count":36,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["molecules25143160"],"URL":"https:\/\/doi.org\/10.3390\/molecules25143160","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2020,7,10]]}}}