{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:46:43Z","timestamp":1787028403204,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,6,26]],"date-time":"2017-06-26T00:00:00Z","timestamp":1498435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ginsenoside Rh2 (Rh2) is an active principal ingredient contained in ginseng (Panax ginseng Meyer), a medicinal herb used to enhance health worldwide. The present study is designed to investigate the effect of Rh2 on myocardial fibrosis in diabetic rats. In a streptozotocin-induced model of type-1 diabetic rats (STZ-diabetic rats), the increased fasting blood glucose levels and heart weight\/body weight (HW\/BW) ratio were substantially alleviated by Rh2. Moreover, Rh2 improved cardiac performance in STZ-diabetic rats. Histological results from Masson staining showed that Rh2 attenuated cardiac fibrosis in STZ-diabetic rats. The effects of Rh2 were reversed by GSK0660 at a dose sufficient to inhibit peroxisome proliferator-activated receptor \u03b4 (PPAR\u03b4) in STZ-diabetic rats. The role of PPAR\u03b4 was subsequently investigated in vitro. Rh2 restored the decreased PPAR\u03b4 expression level in high glucose-cultured cardiomyocytes. Moreover, increased protein levels of fibrotic signals, including signal transducer and activator of transcription 3 (STAT3), connective tissue growth factor (CCN2) and fibronectin, were reduced by Rh2 in high glucose-cultured cardiomyocytes. These effects of Rh2 were reversed by GSK0660 or siRNA specific for PPAR\u03b4 Taken together, PPAR\u03b4 activation may inhibit STAT3 activation to reduce CCN2 and fibronectin expression in diabetic rats with cardiac fibrosis. Moreover, Rh2 improves cardiac function and fibrosis by increasing PPAR\u03b4 signaling. Therefore, Rh2 is suitable to develop as an alternative remedy for cardiac fibrosis.<\/jats:p>","DOI":"10.3390\/ijms18071364","type":"journal-article","created":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T02:58:05Z","timestamp":1498532285000},"page":"1364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Ginsenoside Rh2 Improves Cardiac Fibrosis via PPAR\u03b4\u2013STAT3 Signaling in Type 1-Like Diabetic Rats"],"prefix":"10.3390","volume":"18","author":[{"given":"Shih-Hsiang","family":"Lo","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Zhongxing Branch of Taipei City Hospital, Taipei 10341, Taiwan"},{"name":"Department of Nursing, Tzu Chi University of Science and Technology, Hualien 97041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Tien","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pathology, E-DA Hospital, I-Shou University, Yanchao, Kaohsiung 82401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho-Shan","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Nursing, Tzu Chi University of Science and Technology, Hualien 97041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiang-Shan","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Nursing, Tzu Chi University of Science and Technology, Hualien 97041, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juei-Tang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan 71003, Taiwan"},{"name":"Institute of Medical Sciences, Chang Jung Christian University, Guiren, Tainan 71101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhih-Cherng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan 71003, Taiwan"},{"name":"Department of Pharmacy, Chia Nan University of Pharmacy &amp; Science, Jean-Tae 71701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1475-2840-2-1","article-title":"Influence of diabetes mellitus on heart failure risk and outcome","volume":"2","author":"Bauters","year":"2003","journal-title":"Cardiovasc. 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