{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T18:18:48Z","timestamp":1774635528949,"version":"3.50.1"},"reference-count":47,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The areca nut is one of the most commonly consumed psychoactive substances worldwide, with an estimated consumption by approximately 10% of the world\u2019s population, especially in some regions of South Asia, East Africa, and the tropical Pacific. Arecoline, the major areca nut alkaloid, has been classified as carcinogenic to humans as it adversely affects various organs, including the brain, heart, lungs, gastrointestinal tract, and reproductive organs. Earlier studies have established a link between areca nut chewing and cardiac arrhythmias, and yet research pertaining to the mechanisms underlying cardiotoxicity caused by arecoline is still preliminary. The main purpose of this study is to test the hypothesis that arecoline causes cardiac fibrosis through transforming growth factor-\u03b2 (TGF-\u03b2)\/Smad-mediated signaling pathways. Male Wistar rats were injected intraperitoneally with low (5\u2009mg\/kg\/day) or high (50\u2009mg\/kg\/day) doses of arecoline for 3\u2009weeks. Results from Masson\u2019s trichrome staining indicated that arecoline could induce cardiac fibrosis through collagen accumulation. Western blot analysis showed that TGF-\u03b2 and p-Smad2\/3 protein expression levels were markedly higher in the arecoline-injected rat hearts than in those of the control rats. Moreover, arecoline upregulated other fibrotic-related proteins, including SP1-mediated connective tissue growth factor expression. Tissue-type plasminogen activator and its inhibitor, plasminogen activator inhibitor, and matrix metalloproteinase (MMP) 9 were upregulated, and the inhibitor of MMP9 was downregulated. This study provides novel insight into the molecular mechanisms underlying arecoline-induced cardiac fibrosis. Taken together, the areca nut is a harmful substance, and the detrimental effects of arecoline on the heart are similar to that caused by oral submucous fibrosis.<\/jats:p>","DOI":"10.1515\/biol-2021-0116","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T23:25:22Z","timestamp":1635895522000},"page":"1182-1192","source":"Crossref","is-referenced-by-count":17,"title":["The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats"],"prefix":"10.1515","volume":"16","author":[{"given":"Chang-Wen","family":"Ku","sequence":"first","affiliation":[{"name":"Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation , Hualien , Taiwan"},{"name":"Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation , Hualien , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia Hsuan","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Nursing, MeiHo University , Pingtung , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu-Chung","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, College of Medical and Health Science, Asia University , Taichung , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsung-Jung","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation , Hualien , Taiwan"},{"name":"Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation , Hualien , Taiwan"},{"name":"School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University , Hualien , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ray-Jade","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University , Taipei 11031 , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Velmurugan Bharath","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Asia University , Taichung , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Yuan","family":"Lin","sequence":"additional","affiliation":[{"name":"The Department of Family Medicine, China Medical University Hospital , Taichung , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, Asia University , Taichung , Taiwan"},{"name":"Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation , Hualien , Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital , Taichung , Taiwan"},{"name":"Center of General Education, Tzu Chi University of Science and Technology , Hualien , Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, China Medical University Hospital , Taichung 404 , Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"2026011608552374282_j_biol-2021-0116_ref_001","doi-asserted-by":"crossref","unstructured":"Nelson BS\n, \nHeischober B\n. 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