{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:23:31Z","timestamp":1789845811469,"version":"4.0.1"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T00:00:00Z","timestamp":1662940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003712","name":"Korea Food Research Institute (KFRI)","doi-asserted-by":"publisher","award":["E 0210203"],"award-info":[{"award-number":["E 0210203"]}],"id":[{"id":"10.13039\/501100003712","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Theobromine is mainly found in plant foods, such as tea; the primary source of theobromine is the seeds of the Theobroma cacao tree. Theobromine is an alkaloid belonging to the methylxanthine class of drugs, and it is similar\u00a0to theophylline and caffeine. Theobromine is known for its efficacy and role in health and disorder prevention. We evaluated the effects of theobromine on macrophage function, including the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-\u03baB). Theobromine significantly stimulated the production of nitric oxide (NO) and prostaglandin E2 through immune responses, which relate to the increased expression of inducible nitric oxide synthase and cyclooxygenase-2. Additionally, theobromine increased the production of inflammatory cytokines, including tumor necrosis factor-\u03b1 and interleukin-6 in macrophages. Additionally, theobromine induced the translocation and activity of NF-\u03baB in a concentration-dependent manner. Consistent with these results, the phosphorylation level of MAPKs was increased in theobromine-stimulated macrophages. Collectively, these data revealed that theobromine acts as an immune response stimulator via the NF-\u03baB and MAPKs signaling pathways. Thus, theobromine might have protective effects against inflammatory disorders.<\/jats:p>","DOI":"10.3390\/cimb44090289","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T20:52:25Z","timestamp":1663015945000},"page":"4216-4228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Immunostimulatory Activities of Theobromine on Macrophages via the Activation of MAPK and NF-\u03baB Signaling Pathways"],"prefix":"10.3390","volume":"44","author":[{"given":"Hee-Weon","family":"Lee","sequence":"first","affiliation":[{"name":"Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun 55365, Korea"},{"name":"School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Wook","family":"Choi","sequence":"additional","affiliation":[{"name":"Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun 55365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3329-2279","authenticated-orcid":false,"given":"Sang Keun","family":"Ha","sequence":"additional","affiliation":[{"name":"Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun 55365, Korea"},{"name":"Division of Food Biotechnology, University of Science and Technology, Daejeon 35408, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,12]]},"reference":[{"key":"ref_1","first-page":"BR325","article-title":"Antioxidant and prooxidant properties of caffeine, theobromine and xanthine","volume":"9","author":"Azam","year":"2003","journal-title":"Med. 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