{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:52:10Z","timestamp":1778770330421,"version":"3.51.4"},"reference-count":25,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ahn-Gook Pharmaceutical Co., LTD","award":["none"],"award-info":[{"award-number":["none"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Background: Hederacoside C from ivy leaf dry extracts (HH) and berberine from Coptidis rhizome dry extracts (CR) can be combined (HHCR) as a herbal product. Previous studies have demonstrated that HHCR has antitussive and expectorant effects in animal models of respiratory disease. However, the therapeutic effects of HHCR on respiratory diseases in humans have not been well-studied. Therefore, we aimed to clarify the effectiveness of HHCR in patients with chronic bronchitis and bronchiectasis. Methods: This was a multicenter (10 university teaching hospitals), open-label, prospective, single-arm, observational study. Consecutive patients with chronic bronchitis and bronchiectasis were included. Patients were orally treated with HHCR daily for 12 weeks. St. George\u2019s Respiratory Questionnaire (SGRQ) scores and bronchitis severity scores (BSS) were measured at baseline and at the end of the 12-week study. Results: In total, 376 patients were enrolled, of which 304 were finally included in the study, including 236 males and 68 females with a median age of 69 years (range: 37\u201388 years). After 12 weeks of HHCR treatment, there was a significant improvement in SGRQ score (baseline, 32.52 \u00b1 16.93 vs. end of study, 29.08 \u00b1 15.16; p &lt; 0.0001) and a significant reduction in BSS (baseline, 7.16 \u00b1 2.63 vs. end of study, 4.72 \u00b1 2.45; p &lt; 0.0001). During the study, 14 patients concomitantly used an inhaled corticosteroid and 83 patients used an inhaled bronchodilator. HHCR also had significant positive effects on these patients in terms of SGRQ score and BSS. No serious adverse drug reactions occurred during HHCR treatment. Conclusions: treatment with HHCR improved the SGRQ score and BSS in patients with chronic bronchitis and bronchiectasis. HHCR may be a new therapeutic option for chronic bronchitis and bronchiectasis. Large-scale, randomized, double-blind, placebo-controlled clinical trials are warranted.<\/jats:p>","DOI":"10.3390\/ijerph18084024","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T03:04:06Z","timestamp":1618196646000},"page":"4024","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effects of a Mixture of Ivy Leaf Extract and Coptidis rhizome on Patients with Chronic Bronchitis and Bronchiectasis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7779-4000","authenticated-orcid":false,"given":"Goohyeon","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan 31116, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Il","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonology, Chonnam National University Hospital, Chonnam 61469, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0454-6118","authenticated-orcid":false,"given":"Seoung Ju","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonology, Allergy and Critical Care Medicine, Jeonbuk National University Medical School, Cheonbuk 54907, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Yong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonology, Allergy and Critical Care Medicine, Korea University Guro Hospital, Seoul 08308, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonology, College of Medicine, The Catholic University, Uijeongbu 11765, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2075-4702","authenticated-orcid":false,"given":"Seong Hoon","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonology, Pusan National University Yangsan Hospital, Pusan 49241, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keu Sung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Ajou University Hospital, Suwon 16499, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1525-1745","authenticated-orcid":false,"given":"Min Kwang","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Respiratory Medicine, Gangnam Severance Hospital, Seoul 06273, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hak-Ryul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Respiratory Medicine, Wonkwang University Hospital, Iksan 54538, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaeho","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Respiratory Medicine, Catholic Kwandong University International St. Mary\u2019s Hospital, Incheon 22711, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1164\/rccm.201210-1843CI","article-title":"Chronic bronchitis and chronic obstructive pulmonary disease","volume":"187","author":"Kim","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1177\/0394632015584724","article-title":"Mucociliary clearance techniques for treating non-cystic fibrosis bronchiectasis: Is there evidence?","volume":"28","author":"Snijders","year":"2015","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_3","first-page":"193","article-title":"Research on export current situation and countermeasure of Coptis chinensis from Shizhu county","volume":"15","author":"Kong","year":"2013","journal-title":"Morder. Chin. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.jep.2013.07.008","article-title":"Inhibitory effect of Coptis chinensis on inflammation in LPS-induced endotoxemia","volume":"149","author":"Choi","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_5","first-page":"116","article-title":"Berberine suppresses interleukin-1beta-Induced MUC5AC gene expression in human airway epithelial cells","volume":"18","author":"Kim","year":"2011","journal-title":"J. Rhinol."},{"key":"ref_6","first-page":"229","article-title":"Relaxant action mechanism of berberine identified as the active principle of Argemone ochroleuca Sweet in guinea-pig tracheal smooth muscle","volume":"60","author":"Navarrete","year":"2008","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_7","first-page":"440","article-title":"Acute anti-inflammatory activity of four saponins isolated from ivy: Alpha-hederin, hederasaponin-C, hederacolchiside-E and hederacolchiside-F in carrageenan-induced rat paw edema","volume":"12","author":"Gepdiremen","year":"2005","journal-title":"Phytomedicine Int. J. Phytother. Phytopharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4236\/cm.2022.131001","article-title":"Cellular stress response mechanisms of Rhizoma coptidis: A systematic review","volume":"13","author":"Wang","year":"2018","journal-title":"Chin. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"819","DOI":"10.3349\/ymj.2015.56.3.819","article-title":"Expectorant and antitussive effect of Hedera helix and Rhizoma coptidis extracts mixture","volume":"56","author":"Song","year":"2015","journal-title":"Yonsei Med. J."},{"key":"ref_10","first-page":"798","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization Global Initiative for Chronic Obstructive Lung Disease (GOLD): Executive summary","volume":"46","author":"Pauwels","year":"2001","journal-title":"Respir. Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1185\/03007995.2013.832183","article-title":"Positioning of the Bronchitis Severity Score (BSS) for standardised use in clinical studies","volume":"29","author":"Matthys","year":"2013","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1055\/s-0034-1377332","article-title":"Assessment of the effect of pharmacotherapy in common cold\/acute bronchitis\u2014 The Bronchitis Severity Scale (BSS)","volume":"68","author":"Kardos","year":"2014","journal-title":"Pneumologie"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Polverino, E., Goeminne, P.C., McDonnell, M.J., Aliberti, S., Marshall, S.E., Loebinger, M.R., Murris, M., Cant\u00f3n, R., Torres, A., and Dimakou, K. (2017). European Respiratory Society guidelines for the management of adult bronchiectasis. Eur. Respir. J., 50.","DOI":"10.1183\/13993003.00629-2017"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/j.rmed.2006.03.012","article-title":"Characterisation of the onset and presenting clinical features of adult bronchiectasis","volume":"100","author":"King","year":"2006","journal-title":"Respir. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1164\/rccm.201203-0487OC","article-title":"Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis","volume":"186","author":"Chalmers","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1183\/09031936.02.00284602","article-title":"A comparison of serial computed tomography and functional change in bronchiectasis","volume":"20","author":"Sheehan","year":"2002","journal-title":"Eur. Respir. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1164\/rccm.201309-1575OC","article-title":"The bronchiectasis severity index. An international derivation and validation study","volume":"189","author":"Chalmers","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1183\/13993003.01899-2015","article-title":"Clinical phenotypes in adult patients with bronchiectasis","volume":"47","author":"Aliberti","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1378\/chest.09-2932","article-title":"Longitudinal growth and lung function in pediatric non-cystic fibrosis bronchiectasis: What influences lung function stability?","volume":"138","author":"Kapur","year":"2010","journal-title":"Chest"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chalmers, J.D., Aliberti, S., Polverino, E., Vendrell, M., Crichton, M., Loebinger, M., Dimakou, K., Clifton, I., Van Der Eerden, M., and Rohde, G. (2016). The EMBARC European Bronchiectasis Registry: Protocol for an international observational study. ERJ Open Res., 2.","DOI":"10.1183\/23120541.00081-2015"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1183\/09031936.00188108","article-title":"Quality of life and dyspnoea in patients treated with bosentan for idiopathic pulmonary fibrosis (BUILD-1)","volume":"35","author":"Raghu","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1056\/NEJMoa0805800","article-title":"UPLIFT Study: The effects of long-term therapy with inhaled tiotropium in chronic obstructive pulmonary disease. Evaluation of: Tashkin, D.P.; Celli, B.; Senn, S.: A 4-year trial of tiotropium in chronic obstructive pulmonary disease","volume":"359","author":"Antoniu","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s10753-019-01139-2","article-title":"Hederacoside-C Inhibition of Staphylococcus aureus-Induced Mastitis via TLR2 & TLR4 and Their Downstream Signaling NF-\u03baB and MAPKs Pathways In Vivo and In Vitro","volume":"43","author":"Akhtar","year":"2020","journal-title":"Inflammation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103767","DOI":"10.1016\/j.micpath.2019.103767","article-title":"Anti-inflammatory effects of Hederacoside-C on Staphylococcus aureus induced inflammation via TLRs and their downstream signal pathway in vivo and in vitro","volume":"137","author":"Akhtar","year":"2019","journal-title":"Microbial. Pathog."},{"key":"ref_25","first-page":"859","article-title":"Mucolytics, expectorants, and mucokinetic medications","volume":"52","author":"Rubin","year":"2007","journal-title":"Respir. Care."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/8\/4024\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:59:29Z","timestamp":1760363969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/8\/4024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,12]]},"references-count":25,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijerph18084024"],"URL":"https:\/\/doi.org\/10.3390\/ijerph18084024","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,12]]}}}