{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:27:52Z","timestamp":1785414472056,"version":"3.56.0"},"reference-count":17,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kaohsiung Municipal Min-Sheng Hospital Project","award":["KMSH-11303"],"award-info":[{"award-number":["KMSH-11303"]}]},{"name":"National Science and Technology Council","award":["NSTC 113-2320-B-127-001"],"award-info":[{"award-number":["NSTC 113-2320-B-127-001"]}]},{"name":"National Science and Technology Council","award":["NSTC 112-2321-B-037-007"],"award-info":[{"award-number":["NSTC 112-2321-B-037-007"]}]},{"award":["NSTC 113-2320-B-127-001"],"award-info":[{"award-number":["NSTC 113-2320-B-127-001"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NSTC 112-2321-B-037-007"],"award-info":[{"award-number":["NSTC 112-2321-B-037-007"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministry of Science and Technology","award":["MOST 111-2320-B-037-020-MY3"],"award-info":[{"award-number":["MOST 111-2320-B-037-020-MY3"]}]},{"DOI":"10.13039\/501100004694","name":"Kaohsiung Medical University","doi-asserted-by":"crossref","award":["KMU-TC112A03-3"],"award-info":[{"award-number":["KMU-TC112A03-3"]}],"id":[{"id":"10.13039\/501100004694","id-type":"DOI","asserted-by":"crossref"}]},{"award":["KMU-TC112A03-3"],"award-info":[{"award-number":["KMU-TC112A03-3"]}],"id":[{"id":"https:\/\/ror.org\/03gk81f96","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Introduction:\u00a0Neisseria gonorrhoeae, a bacterium responsible for gonorrhea, can spread through oral sex, causing pharyngeal gonorrhea, which is also a leading cause of urethritis in outpatient clinics. This study investigated whether tea tree oil (TTO) alone or in combination with other natural products could serve as an effective alternative to chlorhexidine in preventing the spread of oral gonorrhea. Methods: An in vitro model was developed using T84 epithelial cells as a mucosal layer and Neisseria gonorrhoeae strain MS11. The study assessed the minimal inhibitory concentration (MIC), bacterial adherence, invasion, and transmigration across the mucosal barrier. Berberine (BB), a major and bioactive alkaloid derived from Coptis chinensis, was tested with and without TTO in MIC assays and epithelial cell viability tests. Ceftriaxone was used as a positive control. Results: The MIC values for TTO, BB, and ceftriaxone against the MS11 strain were determined to be 0.2%, 5 \u03bcg\/mL, and 0.0125 \u03bcg\/mL, respectively. Notably, the combination of TTO with BB demonstrated a synergistic effect, reducing the MIC to 0.000625% TTO + 1.25 \u03bcg\/mL BB. This combination provided the strongest protective effect. No cytotoxicity was observed in the epithelial cell viability tests for 0.2% diluted TTO, 5 \u03bcg\/mL BB, or the combination of 0.000625% TTO + 1.25 \u03bcg\/mL BB. Conclusions: BB, when combined with TTO, exhibited a synergistic antimicrobial effect against Neisseria gonorrhoeae strain MS11 in the T84 mucosal model. These findings highlight the potential of this combination as a natural alternative to chlorhexidine gluconate for managing oral gonorrhea.<\/jats:p>","DOI":"10.3390\/antibiotics15040392","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:49:02Z","timestamp":1776070142000},"page":"392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Effect of the Mucosa-Friendly Agents Berberine and Tea Tree Oil on Mucosal Protection Against Neisseria gonorrhoeae in an In Vitro T84 Cell Mucosa Model"],"prefix":"10.3390","volume":"15","author":[{"given":"Mon-Der","family":"Cho","sequence":"first","affiliation":[{"name":"Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"},{"name":"Department of Urology, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung 802511, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Yu","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-9479","authenticated-orcid":false,"given":"Jung-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung 824005, Taiwan"},{"name":"Department of Medical Science and Biotechnology, I-Shou University, Kaohsiung 824005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ming","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung 907101, Taiwan"},{"name":"Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Ying","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Tzu Chi University, Hualien 970374, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4674-3363","authenticated-orcid":false,"given":"Yi-Hong","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung 907101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2549-4193","authenticated-orcid":false,"given":"Fang-Rong","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"},{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804201, Taiwan"},{"name":"Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). 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(2025). Exploring the Role of Berberine as a Molecular Disruptor in Antimicrobial Strategies. Pharmaceuticals, 18.","DOI":"10.3390\/ph18070947"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yang, X., Wang, Y., Li, L., Tang, D., Yan, Z., Li, M., Jiang, J., and Bi, D. (2025). Berberine and its nanoformulations and extracts: Potential strategies and future perspectives against multi-drug resistant bacterial infections. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1643409"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4475","DOI":"10.2147\/IDR.S278020","article-title":"Evaluation of Drugs with Therapeutic Potential for Susceptibility of Neisseria gonorrhoeae Isolates from 8 Provinces in China from 2018","volume":"13","author":"Zheng","year":"2020","journal-title":"Infect. 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Biotechnol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/4\/392\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:16:23Z","timestamp":1776140183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/4\/392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,12]]},"references-count":17,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["antibiotics15040392"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15040392","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,12]]}}}