{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:18:12Z","timestamp":1790281092583,"version":"4.1.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013996","name":"Global Health Innovative Technology Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Tuberculosis (TB) is the global health problem with the second highest number of deaths from a communicable disease after COVID-19. Although TB is curable, poor health infrastructure, long and grueling TB treatments have led to the spread of TB pandemic with alarmingly increasing multidrug-resistant (MDR)-TB prevalence. Alternative host modulating therapies can be employed to improve TB drug efficacies or dampen the exaggerated inflammatory responses to improve lung function. Here, we investigated the adjunct therapy of natural immune-modulatory compound berberine in C57BL\/6 mouse model of pulmonary TB. Berberine treatment did not affect <jats:italic>Mtb<\/jats:italic> growth in axenic cultures; however, it showed increased bacterial killing in primary murine bone marrow-derived macrophages and human monocyte-derived macrophages. <jats:italic>Ad libitum<\/jats:italic> berberine administration was beneficial to the host in combination with rifampicin and isoniazid. Berberine adjunctive treatment resulted in decreased lung pathology with no additive or synergistic effects on bacterial burdens in mice. Lung immune cell flow cytometry analysis showed that adjunctive berberine treatment decreased neutrophil, CD11b<jats:sup>+<\/jats:sup> dendritic cell and recruited interstitial macrophage numbers. Late onset of adjunctive berberine treatment resulted in a similar phenotype with consistently reduced numbers of neutrophils both in lungs and the spleen. Together, our results suggest that berberine can be supplemented as an immunomodulatory agent depending on the disease stage and inflammatory status of the host.<\/jats:p>","DOI":"10.3389\/fimmu.2021.656419","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T22:53:40Z","timestamp":1634770420000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Evaluation of Berberine as an Adjunct to TB Treatment"],"prefix":"10.3389","volume":"12","author":[{"given":"Mumin","family":"Ozturk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius E.","family":"Chia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudranil","family":"Hazra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd","family":"Saqib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeng\u00a0A.","family":"Maine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reto","family":"Guler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harukazu","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibhuti B.","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Brombacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suraj P.","family":"Parihar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"B1","article-title":"Global Tuberculosis Report 2020","volume-title":"Global Tuberculosis Programme","year":"2020"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1002152","DOI":"10.1371\/journal.pmed.1002152","article-title":"The Global Burden of Latent Tuberculosis Infection: A Re-Estimation Using Mathematical Modelling","volume":"13","author":"Houben","year":"2016","journal-title":"PloS Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"k2738","DOI":"10.1136\/bmj.k2738","article-title":"Revisiting the Timetable of Tuberculosis","volume":"362","author":"Behr","year":"2018","journal-title":"BMJ"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2015.04.003","article-title":"Latent Tuberculosis Infection \u2013 Revisiting and Revising Concepts","volume":"95","author":"Salgame","year":"2015","journal-title":"Tuberculosis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1917","article-title":"Estimating the Future Burden of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis in India, the Philippines, Russia, and South Africa: A Mathematical Modelling Study","volume":"17","author":"Sharma","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"B6","unstructured":"Price of a Pandemic"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1917","article-title":"Host-Directed Drug Therapy for Tuberculosis","volume":"11","author":"Guler","year":"2015","journal-title":"Nat Chem Biol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/s41385-019-0226-5","article-title":"Therapeutic Host-Directed Strategies to Improve Outcome in Tuberculosis","volume":"13","author":"Young","year":"2020","journal-title":"Mucosal Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-015-0531-3","article-title":"Pathology and Immune Reactivity: Understanding Multidimensionality in Pulmonary Tuberculosis","volume":"38","author":"Dorhoi","year":"2016","journal-title":"Semin Immunopathol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2003.09.002","article-title":"The Anti-Inflammatory Potential of Berberine In Vitro and In Vivo","volume":"203","author":"Kuo","year":"2004","journal-title":"Cancer Lett"},{"key":"B11","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/S0924-8579(03)00085-2","article-title":"Berberis Aetnensis C. 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