{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:41:45Z","timestamp":1786725705574,"version":"build-2736575974"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>\n                    Food allergies (FAs) significantly impact quality of life. Allergen-specific immunotherapy (AIT) shows promise but faces limitations such as prolonged treatment duration, systemic side effects, and poor compliance, especially in pediatric and elderly populations. Complementary and alternative medicine (CAM) may enhance AIT efficacy and safety, yet the mechanisms underlying immune tolerance remain poorly understood. This study employed an integrated\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    approach combining network pharmacology, molecular simulation, and metabolomics to investigate anti-allergic\n                    <jats:italic toggle=\"yes\">Jamu<\/jats:italic>\n                    medicinal plants in FA. Active compounds from 13 medicinal plants were analyzed to predict key targets and pathways. Molecular docking and dynamics simulations assessed compound-target binding affinities, while metabolomics evaluated tissue distribution and bioavailability in lymphoid tissues. The results identified transforming growth factor-beta 1 (TGFB1) as a key target associated with the FoxO signaling pathway and Th17 cell differentiation, both of which are critical for promoting allergic tolerance. MAPK1 and MAPK14 emerged as additional targets, providing insights into the mechanisms of allergy development. Molecular simulations demonstrated strong binding affinities, with quercetin (\u22129.1 kcal\/mol) and genistein (\u22128.1 kcal\/mol) binding to TGFB1, and isoprocurcumenol (\u22127.1 kcal\/mol) and dicinnamoylmethane (\u221210.1 kcal\/mol) binding to MAPK1 and MAPK14, respectively. Metabolomic analysis further showed high genistein accumulation in lymph nodes. In summary, these findings suggest that CAM-AIT integration could significantly improve FA therapeutic outcomes by promoting immune tolerance and modulating inflammatory pathways.\n                  <\/jats:p>","DOI":"10.4103\/japtr.japtr_283_25","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T16:00:15Z","timestamp":1778342415000},"page":"155-162","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Integrative multi-omics, network pharmacology, and molecular simulation of herbal compounds targeting immune tolerance mechanisms in food allergy"],"prefix":"10.4103","volume":"17","author":[{"given":"Honey Dzikri","family":"Marhaeny","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delis","family":"Susilawati","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia"},{"name":"Division of Infectious Disease Control, Center for Infectious Disease, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fittree","family":"Hayeeawaema","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma Nuril","family":"Aliyah","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Health Science, Maulana Malik Ibrahim State Islamic University, Malang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf Alif","family":"Pratama","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wa Ode","family":"Nurfinti","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Halu Oleo University, Kendari, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hijrawati Ayu","family":"Wardani","sequence":"additional","affiliation":[{"name":"Departement of Pharmacy, Pelamonia Institute of Health Sciences, Makassar, Indonesia"},{"name":"Faculty of Pharmacy, University of Indonesia, Depok, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal Akhmal","family":"Muslikh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmacy, Hang Tuah University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeline Felisca","family":"Tanujaya","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Dzulfikri","family":"Nurhan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia"},{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tri","family":"Widiandani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bambang Tri","family":"Purwanto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andang","family":"Miatmoko","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junaidi","family":"Khotib","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"R1-20260511","doi-asserted-by":"crossref","first-page":"996","DOI":"10.3389\/fimmu.2020.00996","article-title":"A comprehensive review on natural bioactive compounds and probiotics as potential therapeutics in food allergy treatment","volume":"11","author":"Pratap","year":"2020","journal-title":"Front Immunol"},{"key":"R2-20260511","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nm.2754","article-title":"Therapies for allergic inflammation: Refining strategies to induce tolerance","volume":"18","author":"Akdis","year":"2012","journal-title":"Nat Med"},{"key":"R3-20260511","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jaip.2017.01.017","article-title":"Complementary and alternative medicine use among allergy practices: Results of a nationwide survey of allergists","volume":"6","author":"Land","year":"2018","journal-title":"J Allergy Clin Immunol Pract"},{"key":"R4-20260511","doi-asserted-by":"crossref","first-page":"196","DOI":"10.46542\/pe.2023.234.196202","article-title":"Investigating the anti-allergic activity of Phyllanthus niruri via MALT1 protease inhibition: An in silico approach","volume":"23","author":"Marhaeny","year":"2023","journal-title":"Pharm Educ"},{"key":"R5-20260511","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3390\/ijms25010467","article-title":"Modulation of the immune response to allergies using alternative functional foods","volume":"25","author":"L\u00f3pez-Enr\u00edquez","year":"2023","journal-title":"Int J Mol Sci"},{"key":"R6-20260511","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s12906-021-03316-z","article-title":"The use of complementary and alternative medicine by adults with allergies: A Czech national representative survey","volume":"21","author":"Pokladnikova","year":"2021","journal-title":"BMC Complement Med Ther"},{"key":"R7-20260511","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.jaci.2015.04.029","article-title":"Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (food allergy herbal formula-2) for food allergy","volume":"136","author":"Wang","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"R8-20260511","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.iac.2017.09.012","article-title":"Complementary and alternative medicine for treatment of food allergy","volume":"38","author":"Li","year":"2018","journal-title":"Immunol Allergy Clin North Am"},{"key":"R9-20260511","doi-asserted-by":"crossref","first-page":"1174907","DOI":"10.3389\/fimmu.2023.1174907","article-title":"Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature","volume":"14","author":"Srivastava","year":"2023","journal-title":"Front Immunol"},{"key":"R10-20260511","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1007\/s11655-016-2526-x","article-title":"Recent highlights of Chinese herbs in treatment of allergic disease: Acting via mitogen-activated protein kinase signal pathway","volume":"23","author":"He","year":"2017","journal-title":"Chin J Integr Med"},{"key":"R11-20260511","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.drudis.2011.07.010","article-title":"Finding a better path to drug selectivity","volume":"16","author":"Kawasaki","year":"2011","journal-title":"Drug Discov Today"},{"key":"R13-20260511","doi-asserted-by":"crossref","first-page":"10989","DOI":"10.3390\/app142310989","article-title":"Impact of childhood food allergy on quality of life: A systematic review","volume":"14","author":"Valero-Moreno","year":"2024","journal-title":"Appl Sci"},{"key":"R14-20260511","doi-asserted-by":"crossref","first-page":"108","DOI":"10.2500\/aap.2020.41.200001","article-title":"Safety of allergen immunotherapy in North America from 2008-2017: Lessons learned from the ACAAI\/AAAAI national surveillance study of adverse reactions to allergen immunotherapy","volume":"41","author":"Bernstein","year":"2020","journal-title":"Allergy Asthma Proc"},{"key":"R15-20260511","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.jaci.2019.07.030","article-title":"Long-term sublingual immunotherapy for peanut allergy in children: Clinical and immunologic evidence of desensitization","volume":"144","author":"Kim","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"R16-20260511","doi-asserted-by":"crossref","first-page":"65","DOI":"10.13057\/asianjethnobiol\/y060108","article-title":"Plants as herbal medicine at Nguter traditional market, Sukoharjo, Central Java, Indonesia","volume":"6","author":"Mardiyanto","year":"2023","journal-title":"Asian J Ethnobiol"},{"key":"R17-20260511","doi-asserted-by":"crossref","first-page":"e0315312","DOI":"10.1371\/journal.pone.0315312","article-title":"Shrimp allergen extract immunotherapy induces prolonged immune tolerance in a gastro-food allergy mouse model","volume":"19","author":"Marhaeny","year":"2024","journal-title":"PLoS One"},{"key":"R18-20260511","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41392-024-01764-w","article-title":"TGF-\u03b2 signaling in health, disease, and therapeutics","volume":"9","author":"Deng","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"R19-20260511","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3390\/epigenomes9020011","article-title":"Induction of DNA demethylation: Strategies and consequences","volume":"9","author":"Carollo","year":"2025","journal-title":"Epigenomes"},{"key":"R20-20260511","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.molmed.2007.08.005","article-title":"TGFbeta1 and Treg cells: Alliance for tolerance","volume":"13","author":"Bommireddy","year":"2007","journal-title":"Trends Mol Med"},{"key":"R21-20260511","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/s41423-023-01036-7","article-title":"Intricacies of TGF-\u03b2 signaling in Treg and Th17 cell biology","volume":"20","author":"Wang","year":"2023","journal-title":"Cell Mol Immunol"},{"key":"R22-20260511","doi-asserted-by":"crossref","first-page":"119223","DOI":"10.1016\/j.bbamcr.2022.119223","article-title":"The effects of post-translational modifications on Th17\/Treg cell differentiation","volume":"1869","author":"Le","year":"2022","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"R23-20260511","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.jaci.2013.12.1037","article-title":"Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3)","volume":"133","author":"Syed","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"R24-20260511","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1084\/jem.20101156","article-title":"PI3 kinase signalling blocks Foxp3 expression by sequestering foxo factors","volume":"207","author":"Merkenschlager","year":"2010","journal-title":"J Exp Med"},{"key":"R25-20260511","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.3389\/fimmu.2019.02530","article-title":"Mucosal immunity and the FOXO1 transcription factors","volume":"10","author":"Graves","year":"2019","journal-title":"Front Immunol"},{"key":"R26-20260511","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.4049\/jimmunol.1500849","article-title":"Foxo1 is a T cell-intrinsic inhibitor of the ROR\u03b3t-Th17 program","volume":"195","author":"Lain\u00e9","year":"2015","journal-title":"J Immunol"},{"key":"R27-20260511","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/ni.1884","article-title":"Foxo proteins cooperatively control the differentiation of Foxp3+regulatory T cells","volume":"11","author":"Ouyang","year":"2010","journal-title":"Nat Immunol"},{"key":"R28-20260511","doi-asserted-by":"crossref","first-page":"51","DOI":"10.46542\/pe.2024.243.5156","article-title":"Pinostrobin and its derivatives as novel anti-breast cancer agents against human oestrogen receptor alpha: In silico studies of ADMET, docking, and molecular dynamics","volume":"24","author":"Susilawati","year":"2024","journal-title":"Pharm Educ"},{"key":"R29-20260511","doi-asserted-by":"crossref","first-page":"100395","DOI":"10.1016\/j.iotech.2023.100395","article-title":"Lymph node targeting for immunotherapy","volume":"20","author":"Wang","year":"2023","journal-title":"Immunooncol Technol"}],"container-title":["Journal of Advanced Pharmaceutical Technology &amp; Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/JAPTR.JAPTR_283_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:24:39Z","timestamp":1786724679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/JAPTR.JAPTR_283_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/japtr.japtr_283_25","relation":{},"ISSN":["2231-4040","0976-2094"],"issn-type":[{"value":"2231-4040","type":"print"},{"value":"0976-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-10-11","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-10","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}