{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:48:11Z","timestamp":1790909291908,"version":"4.1.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>With the development of cardiac rehabilitation (CR), the advantages of combined Chinese and Western medicine cardiac rehabilitation for the treatment of stable coronary artery disease (SCAD) have become increasingly prominent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study was aimed to evaluate the effect of Zhenyuan capsule (a Chinese patented medicine consisting of ginseng berry saponins extracted from the mature berry of Panax Ginseng) on cardiorespiratory fitness (CRF) in patients with SCAD, and explore possible potential candidate molecule.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design and Methods<\/jats:title>\n                    <jats:p>Using a randomized, double-blind, placebo-controlled trial design, 100 patients with SCAD were enrolled and randomly divided into the group taking Zhenyuan capsules (test group, n = 50) and the group taking placebo (control group, n = 50). In both groups, patients were treated with secondary prevention medication for CHD, with the addition of 2 capsules of Zhenyuan capsule 3 times a day for 12 weeks in the test group and 2 capsules of placebo 3 times a day for 12 weeks in the control group, with a follow-up of 1 month after the end of treatment. Subjects completed symptom-limited maximal cardiopulmonary exercise test (CPET) on a bicycle ergometer at 3 time points before enrollment, after 12 weeks of treatment, and after 1 month of follow-up. The main outcome was the increase in metabolic equivalent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both at anaerobic threshold (AT) level and at maximal level, the results of between-group comparisons showed that the test group was significantly better than that of the control group after treatment (AT level: 0.58 \u00b1 0.89 Mets vs. 0.15 \u00b1 1.06 Mets; maximal level: 0.69 \u00b1 0.92 Mets vs. 0.19 \u00b1 0.93 Mets) (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). No serious adverse events occurred in patients in both groups. Serum proteomics studies suggested that insulin-like growth factor II (IGF2) was downregulated in a minority of responders, potentially related to cholesterol metabolism and the PI3K-Akt pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Zhenyuan capsule can significantly improve the CRF of patients with SCAD, and the downregulation of IGF2 observed in a minority of responders suggests IGF2 may be a potential candidate molecule of interest associated with cholesterol metabolism and the PI3K-Akt pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.chictr.org.cn\/showproj.html?proj=53361<\/jats:ext-link>\n                      , identifier ChiCTR2000032818.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1724232","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:55:12Z","timestamp":1769064912000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of ginseng berry saponins on cardiorespiratory fitness in patients with SCAD: a randomized, double-blinded, placebo-controlled trial"],"prefix":"10.3389","volume":"17","author":[{"given":"Yaru","family":"Ge","sequence":"first","affiliation":[{"name":"Beijing Shijitan Hospital affiliated with Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Huan","sequence":"additional","affiliation":[{"name":"Xiyuan Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Sun","sequence":"additional","affiliation":[{"name":"Xiyuan Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Chao","sequence":"additional","affiliation":[{"name":"Xiyuan Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jilin Ji\u2019an Yisheng Company","place":["Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Wang","sequence":"additional","affiliation":[{"name":"Xiyuan Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1001\/jama.292.12.1462","article-title":"Global risk scores and exercise testing for predicting all-cause mortality in a preventive medicine program","volume":"292","author":"Aktas","year":"2004","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1136\/hrt.2007.121558","article-title":"Cardiopulmonary exercise testing and its application","volume":"93","author":"Albouaini","year":"2007","journal-title":"Heart British Card. Soc."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jacc.2015.10.044","article-title":"Exercise-based cardiac rehabilitation for coronary heart disease: cochrane systematic review and meta-analysis","volume":"67","author":"Anderson","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1159\/000343995","article-title":"Insulin-like growth factor 2 in development and disease: a mini-review","volume":"59","author":"Bergman","year":"2013","journal-title":"Gerontology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1056\/NEJMoa070829","article-title":"Optimal medical therapy with or without PCI for stable coronary disease","volume":"356","author":"Boden","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1007\/s40279-021-01442-9","article-title":"Exploring differences in cardiorespiratory fitness response rates across varying doses of exercise training: a retrospective analysis of eight randomized controlled trials","volume":"51","author":"Bonafiglia","year":"2021","journal-title":"Sports Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"633","DOI":"10.2165\/00007256-200838080-00002","article-title":"Autonomic control of heart rate during and after exercise: measurements and implications for monitoring training status","volume":"38","author":"Borresen","year":"2008","journal-title":"Sports Med. Auckl. N.Z."},{"key":"B8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1249\/00005768-198502000-00005","article-title":"Anaerobic threshold: review of the concept and directions for future research","volume":"17","author":"Brooks","year":"1985","journal-title":"Med. and Sci. Sports and Exerc."},{"key":"B9","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1249\/MSS.0b013e31822cb190","article-title":"Correlates of heart rate recovery over 20 years in a healthy population sample","volume":"44","author":"Carnethon","year":"2012","journal-title":"Med. Sci. Sports Exerc."},{"key":"B10","doi-asserted-by":"publisher","first-page":"425","DOI":"10.5142\/jgr.2012.36.4.425","article-title":"Comparison of ginsenoside and phenolic ingredient contents in hydroponically-cultivated ginseng leaves, fruits, and roots","volume":"36","author":"Choi","year":"2012","journal-title":"J. Ginseng Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1056\/NEJM199910283411804","article-title":"Heart-rate recovery immediately after exercise as a predictor of mortality","volume":"341","author":"Cole","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1113\/expphysiol.2009.047548","article-title":"Recovery of heart rate following intense dynamic exercise","volume":"95","author":"Coote","year":"2010","journal-title":"Exp. Physiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1093\/eurheartj\/ehq236","article-title":"Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the cardiac rehabilitation section of the european association of cardiovascular prevention and rehabilitation","volume":"31","author":"Corr\u00e0","year":"2010","journal-title":"Eur. Heart J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1056\/NEJMoa1205361","article-title":"Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease","volume":"367","author":"De Bruyne","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"754794","DOI":"10.3389\/fcvm.2021.754794","article-title":"Efficacy and safety of resistance training for coronary heart disease rehabilitation: a systematic review of randomized controlled trials","volume":"8","author":"Fan","year":"2021","journal-title":"Front. Cardiovasc Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1161\/CIR.0b013e31829b5b44","article-title":"Exercise standards for testing and training: a scientific statement from the American heart association","volume":"128","author":"Fletcher","year":"2013","journal-title":"Circulation"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1056\/NEJMoa0805796","article-title":"A randomized trial of therapies for type 2 diabetes and coronary artery disease","volume":"360","author":"Frye","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1016\/s0735-1097(02)02164-2","article-title":"ACC\/AHA 2002 guideline update for exercise testing: summary article. A report of the American college of cardiology\/american heart association task force on practice guidelines (committee to update the 1997 exercise testing guidelines)","volume":"40","author":"Gibbons","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1097\/HJR.0b013e328336a10d","article-title":"Risk of mortality increases with increasing number of abnormal non-ST parameters recorded during exercise testing","volume":"17","author":"Ho","year":"2010","journal-title":"Eur. J. Cardiovasc. Prev. Rehabilitation"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1016\/0735-1097(94)90150-3","article-title":"Vagally mediated heart rate recovery after exercise is accelerated in athletes but blunted in patients with chronic heart failure","volume":"24","author":"Imai","year":"1994","journal-title":"J. Am. Coll. Cardiol."},{"key":"B21","first-page":"5","article-title":"Circulatory regulation at rest and exercise and the functional assessment of patients with congestive heart failure","volume":"81","author":"Jennings","year":"1990","journal-title":"Circulation"},{"key":"B22","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.amjcard.2012.02.046","article-title":"Prognostic value of late heart rate recovery after treadmill exercise","volume":"110","author":"Johnson","year":"2012","journal-title":"Am. J. Cardiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1001\/jama.2009.681","article-title":"Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis","volume":"301","author":"Kodama","year":"2009","journal-title":"JAMA"},{"key":"B24","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1136\/bjsports-2023-107849","article-title":"Cardiorespiratory fitness is a strong and consistent predictor of morbidity and mortality among adults: an overview of meta-analyses representing over 20.9 million observations from 199 unique cohort studies","volume":"58","author":"Lang","year":"2024","journal-title":"Br. J. Sports Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1093\/eurheartj\/ehy708","article-title":"Peak oxygen uptake and incident coronary heart disease in a healthy population: the HUNT fitness study","volume":"40","author":"Letnes","year":"2019","journal-title":"Eur. Heart J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1056\/NEJMoa1915922","article-title":"Initial invasive or conservative strategy for stable coronary disease","volume":"382","author":"Maron","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.tcm.2017.02.005","article-title":"The role of cardiac rehabilitation in patients with heart disease","volume":"27","author":"McMahon","year":"2017","journal-title":"Trends Cardiovasc. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e27","DOI":"10.1161\/01.CIR.0000136811.45524.2F","article-title":"Cardiopulmonary exercise testing: how do we differentiate the cause of dyspnea?","volume":"110","author":"Milani","year":"2004","journal-title":"Circulation"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.4065\/81.12.1603","article-title":"Understanding the basics of cardiopulmonary exercise testing","volume":"81","author":"Milani","year":"2006","journal-title":"Mayo Clin. Proc."},{"key":"B30","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/s0012-3692(16)31282-x","article-title":"Principles of exercise testing and interpretation","volume":"92","author":"Millsaps","year":"1987","journal-title":"Chest"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1001\/jama.290.12.1600","article-title":"Ability of exercise testing to predict cardiovascular and all-cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study","volume":"290","author":"Mora","year":"2003","journal-title":"JAMA"},{"key":"B32","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1016\/s0002-9149(02)02706-6","article-title":"Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (the framingham heart study)","volume":"90","author":"Morshedi-Meibodi","year":"2002","journal-title":"Am. J. Cardiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1001\/archinte.148.10.2221","article-title":"Cardiopulmonary exercise testing. The clinical value of gas exchange data","volume":"148","author":"Neuberg","year":"1988","journal-title":"Archives Intern. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1001\/jama.295.17.2018","article-title":"Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability","volume":"295","author":"Newman","year":"2006","journal-title":"JAMA"},{"key":"B35","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1001\/jama.1988.03410070073031","article-title":"Cardiac rehabilitation after myocardial infarction. Combined experience of randomized clinical trials","volume":"260","author":"Oldridge","year":"1988","journal-title":"JAMA"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/j.amjcard.2015.01.536","article-title":"Usefulness of the integrated scoring model of treadmill tests to predict myocardial ischemia and silent myocardial ischemia in community-dwelling adults (from the Rancho Bernardo study)","volume":"115","author":"Park","year":"2015","journal-title":"Am. J. Cardiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/cpf.12102","article-title":"Heart rate recovery: autonomic determinants, methods of assessment and association with mortality and cardiovascular diseases","volume":"34","author":"Pe\u00e7anha","year":"2014","journal-title":"Clin. Physiology Funct. Imaging"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e005505","DOI":"10.1161\/JAHA.117.005505","article-title":"Heart rate recovery and risk of cardiovascular events and all-cause mortality: a meta-analysis of prospective cohort studies","volume":"6","author":"Qiu","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"B39","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1093\/hmg\/ddh070","article-title":"Haplotypic analyses of the IGF2-INS-TH gene cluster in relation to cardiovascular risk traits","volume":"13","author":"Rodr\u00edguez","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1111\/j.1365-2796.2011.02434.x","article-title":"Two-minute heart rate recovery after cycle ergometer exercise and all-cause mortality in middle-aged men","volume":"270","author":"Savonen","year":"2011","journal-title":"J. Intern. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"680","DOI":"10.3760\/cma.j.issn.0253-3758.2018.09.004","article-title":"Guideline on the diagnosis and treatment of stable coronary artery disease","volume":"46","year":"2018","journal-title":"Zhonghua Xin Xue Guan Bing Za Zhi"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1056\/NEJMoa1505532","article-title":"Effect of PCI on long-term survival in patients with stable ischemic heart disease","volume":"373","author":"Sedlis","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1016\/s0735-1097(01)01652-7","article-title":"Heart rate recovery: validation and methodologic issues","volume":"38","author":"Shetler","year":"2001","journal-title":"J. Am. Coll. Cardiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.3390\/molecules24132443","article-title":"Chemical structures and pharmacological profiles of ginseng saponins","volume":"24","author":"Shi","year":"2019","journal-title":"Mol. Basel, Switz."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.pcad.2021.11.001","article-title":"Impact of cardiorespiratory fitness on outcomes in cardiac rehabilitation","volume":"70","author":"Tutor","year":"2022","journal-title":"Prog. Cardiovasc. Dis."},{"key":"B47","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.ijcard.2009.01.053","article-title":"Effect of heart-rate recovery on long-term mortality among men and women","volume":"144","author":"W\u00e4ndell","year":"2010","journal-title":"Int. J. Cardiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1142\/S0192415X02000442","article-title":"Effects of American ginseng berry extract on blood glucose levels in ob\/ob mice","volume":"30","author":"Xie","year":"2002","journal-title":"Am. J. Chin. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"4505","DOI":"10.1074\/jbc.M108061200","article-title":"Insulin-like growth factor II plays a central role in atherosclerosis in a mouse model","volume":"277","author":"Zaina","year":"2002","journal-title":"J. Biol. Chem."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1724232\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:55:14Z","timestamp":1769064914000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1724232\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":49,"alternative-id":["10.3389\/fphar.2026.1724232"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1724232","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]},"article-number":"1724232"}}