{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:56:11Z","timestamp":1776401771879,"version":"3.51.2"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012542","name":"Dalin Tzu Chi Hospital","doi-asserted-by":"crossref","award":["DTCRD 114-I-02"],"award-info":[{"award-number":["DTCRD 114-I-02"]}],"id":[{"id":"10.13039\/501100012542","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Patients with rheumatoid arthritis (RA) are found to have a higher risk of dental diseases. Although herbal medicines (HMs) have long been used to treat various conditions, few studies focus on its impact on dental diseases. In this longitudinal cohort study, we assessed the correlation between HM use and risk of dental diseases in RA groups. Materials and Methods: A total of 2359 persons with RA aged 20\u201380 who were free of dental diseases between 2001 and 2010 were retrospectively enrolled from nationwide register-based data. They were then classified into HMs and non-HMs groups based on whether they ever used combined HMs after RA onset. Incidence rate and hazard ratios (HRs) of dental diseases were estimated for both groups by the end of 2013 via fitting Cox proportional hazards model. Results: Incidence rate of dental disease was reported to be lower in the HMs group than in the non-HMs group (90.21 per 1000 person-years versus 106.94 per 1000 person-years, respectively). RA individuals treated with HMs showed a significantly lower risk of dental diseases, especially dental caries, pulpitis, periodontitis, and stomatitis. Among commonly prescribed formulas, eleven herbal products significantly associated with a lower risk of dental diseases, such as Hai-Piao-Xiao, Yan-Hu-Suo, Chuan-Niu-Xi, Mo-Yao, Olibanum, Bei-Mu, Mu-Gua, Gui-Zhi-Shao-Yao-Zhi-Mu-Tang, Shao-Yao-Gan-Cao-Tang, Xue-Fu-Zhu-Yu-Tang, and Ping-Wei-San. Conclusions: The addition of HMs treatment may have advantages to proactively prevent sequent risk of dental disorders for persons with rheumatic diseases. A deeper exploration focusing on pharmacological action is needed to provide more reliable evidence for the improvement of susceptible individuals\u2019 oral hygiene.<\/jats:p>","DOI":"10.3390\/medicina62040767","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T14:02:33Z","timestamp":1776261753000},"page":"767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between the Combined Herbal Medicines and Risk of Dental Diseases in Patients with Rheumatoid Arthritis: Insight from a Nationwide Database"],"prefix":"10.3390","volume":"62","author":[{"given":"Chiu-Hui","family":"Ling","sequence":"first","affiliation":[{"name":"Department of Dentistry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Sports Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan 333325, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-To","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5149-1717","authenticated-orcid":false,"given":"Hanoch","family":"Livneh","sequence":"additional","affiliation":[{"name":"Rehabilitation Counseling Program, Portland State University, Portland, OR 97207-0751, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-0351","authenticated-orcid":false,"given":"Ming-Chi","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9865-7101","authenticated-orcid":false,"given":"Tzung-Yi","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40364-025-00760-8","article-title":"Global, regional and national burden of rheumatoid arthritis from 1990 to 2021, with projections of incidence to 2050: A systematic and comprehensive analysis of the Global Burden of Disease study 2021","volume":"13","author":"Ma","year":"2025","journal-title":"Biomark. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"de Molon, R.S., Rossa, C., Thurlings, R.M., Cirelli, J.A., and Koenders, M.I. (2019). Linkage of periodontitis and rheumatoid arthritis: Current evidence and potential biological interactions. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184541"},{"key":"ref_3","first-page":"I1","article-title":"Burden of rheumatoid arthritis among US medicare population: Co-morbidities, health-care resource utilization and costs","volume":"2","author":"Chen","year":"2018","journal-title":"Rheumatol. Adv. Pract."},{"key":"ref_4","first-page":"441","article-title":"What rheumatologists should know about orofacial manifestations of autoimmune rheumatic diseases","volume":"56","author":"Santana","year":"2016","journal-title":"Rev. Bras. Reumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.2174\/1874312902014010034","article-title":"Oral mucosal lesions and DMFT index assessment in rheumatoid arthritis patients in Birjand, Iran, in 2018","volume":"14","author":"Parvaei","year":"2020","journal-title":"Open Rheumatol. J."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Juan, C.Y., Hsu, C.W., and Lu, M.C. (2022). Increased dental visits in patients with rheumatoid arthritis: A secondary cohort analysis of population based claims data. BMC Oral Health, 22.","DOI":"10.1186\/s12903-022-02661-w"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e195394","DOI":"10.1001\/jamanetworkopen.2019.5394","article-title":"Prevalence of periodontal disease and periodontopathic bacteria in anti-cyclic citrullinated protein antibody-positive at-risk adults without arthritis","volume":"2","author":"Mankia","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1111\/odi.13616","article-title":"The role of TLR4\/MyD88\/NF-\u03baB pathway in periodontitis-induced liver inflammation of rats","volume":"27","author":"Yue","year":"2021","journal-title":"Oral Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1322947","DOI":"10.3389\/fmicb.2024.1322947","article-title":"Potential effects of specific gut microbiota on periodontal disease: A two-sample bidirectional Mendelian randomization study","volume":"15","author":"Xu","year":"2024","journal-title":"Front. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1902\/jop.2015.150397","article-title":"Activation of receptor activator of nuclear factor-\u03baB ligand and matrix metalloproteinase production in periodontal fibroblasts by endothelin signaling","volume":"87","author":"Ruest","year":"2016","journal-title":"J. Periodontol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/ipd.12162","article-title":"Impact of dental caries and its treatment on the quality of life of 12- to 15-year-old adolescents in Benin, Nigeria","volume":"26","author":"Chukwumah","year":"2016","journal-title":"Int. J. Paediatr. Dent."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100562","DOI":"10.1016\/j.oor.2024.100562","article-title":"The impact of emotional distress on suicidal ideation in head and neck cancer patients: A review","volume":"11","author":"Baluni","year":"2024","journal-title":"Oral Oncol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9420034","DOI":"10.26599\/FMH.2025.9420034","article-title":"Beneficial effects of dietary herbs on high-fat diet-induced obesity linking with modulation of gut microbiota","volume":"2","author":"Liu","year":"2025","journal-title":"Food Med. Homol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/1752-153X-7-153","article-title":"Triterpenoid resinous metabolites from the genus Boswellia: Pharmacological activities and potential species-identifying properties","volume":"7","author":"Zhang","year":"2013","journal-title":"Chem. Cent. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9591845","DOI":"10.1155\/2018\/9591845","article-title":"Phytochemical and pharmacological properties of chaenomeles speciosa: An edible medicinal Chinese mugua","volume":"2018","author":"Huang","year":"2018","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1080\/13880209.2022.2107018","article-title":"Danggui Niantong granules ameliorate rheumatoid arthritis by regulating intestinal flora and promoting mitochondrial apoptosis","volume":"60","author":"Lu","year":"2022","journal-title":"Pharm. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103912","DOI":"10.1016\/j.autrev.2025.103912","article-title":"Gut microbiota in rheumatoid arthritis: Mechanistic insights, clinical biomarkers, and translational perspectives","volume":"24","author":"Qi","year":"2025","journal-title":"Autoimmun. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Juan, C.Y., Chen, W.J., Livneh, H., Lu, M.C., and Tsai, T.Y. (2025). The addition of Chinese herbal medicines is effective as a prophylactic treatment against dental diseases for sj\u00f6gren\u2019s syndrome patients: Insight from real-world database. Medicina, 61.","DOI":"10.3390\/medicina61091537"},{"key":"ref_19","unstructured":"(2026, February 01). The Introduction of National Helath Insurance Program, Available online: https:\/\/dep.mohw.gov.tw\/DOS\/cp-5301-62356-113.html."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ctim.2019.05.029","article-title":"Use of Chinese herbal medicines by rheumatoid arthritis patients was associated with lower risk of stroke: A retrospective cohort study","volume":"45","author":"Lai","year":"2019","journal-title":"Complement. Ther. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1681\/ASN.2007121354","article-title":"The secret of immortal time bias in epidemiologic studies","volume":"19","author":"Shariff","year":"2008","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_22","first-page":"1","article-title":"Incorporating development stratification of Taiwan townships into sampling design of large scale health interview survey","volume":"4","author":"Liu","year":"2006","journal-title":"J. Health Manag."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/0895-4356(92)90133-8","article-title":"Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases","volume":"45","author":"Deyo","year":"1992","journal-title":"J. Clin. Epidemiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fimmu.2016.00080","article-title":"Hand to mouth: A systematic review and meta-analysis of the association between rheumatoid arthritis and periodontitis","volume":"7","author":"Fuggle","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s10787-024-01631-8","article-title":"Herbal remedies for oral and dental health: A comprehensive review of their multifaceted mechanisms including antimicrobial, anti-inflammatory, and antioxidant pathways","volume":"33","author":"Anwar","year":"2025","journal-title":"Inflammopharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chen, I.C., Lin, T.-H., Hsieh, Y.-H., Chao, C.-Y., Wu, Y.-R., Chang, K.-H., Lee, M.-C., Lee-Chen, G.-J., and Chen, C.-M. (2018). Formulated Chinese medicine shaoyao gancao tang reduces tau aggregation and exerts neuroprotection through anti-oxidation and anti-inflammation. Oxidative Med. Cell. Longev., 9595741.","DOI":"10.1155\/2018\/9595741"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Shim, K.S., Gu, D.R., Hwang, Y.H., Yang, H., Ryuk, J.A., and Ha, H. (2022). Water extract of fritillariae thunbergii bulbus inhibits RANKL-mediated osteoclastogenesis and ovariectomy-induced trabecular bone loss. Molecules, 27.","DOI":"10.3390\/molecules27010169"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e18311","DOI":"10.1590\/s2175-97902019000218311","article-title":"A review on medicinal plants used for treating ototoxicity and acoustic trauma induced hearing loss","volume":"55","author":"Sheikhshabani","year":"2019","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4103\/jispcd.JISPCD_210_22","article-title":"Role of medicinal herbs in periodontal therapy: A systematic review","volume":"13","author":"Pasupuleti","year":"2023","journal-title":"J. Int. Soc. Prev. Community Dent."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1002\/ptr.6338","article-title":"A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee","volume":"33","author":"Majeed","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e41028","DOI":"10.1097\/MD.0000000000041028","article-title":"Network pharmacology unveils the active components and potential mechanism of traditional efficacy of Mugua","volume":"103","author":"Wu","year":"2024","journal-title":"Medicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"603","DOI":"10.4103\/jisp.jisp_12_17","article-title":"Traditionally used herbal medicines with antibacterial effect on Aggegatibacter actinomycetemcomitans: Boswellia serrata and Nigella sativa","volume":"20","author":"Maraghehpour","year":"2016","journal-title":"J. Indian Soc. Periodontol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Cao, M., Shang, Z., Xu, J., Chen, X., Zhu, Z., Wang, W., Wei, X., Zhou, X., and Bai, Y. (2025). Research progress on the antibacterial activity of natural flavonoids. Antibiotics, 14.","DOI":"10.3390\/antibiotics14040334"},{"key":"ref_34","first-page":"1914","article-title":"Commiphora myrrha inhibits itch-associated histamine and IL-31 production in stimulated mast cells","volume":"18","author":"Shin","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Han, H., Li, D., Fan, Y., Liu, M., Ren, H., and Liu, L. (2024). Botanical characterization, phytochemistry, biosynthesis, pharmacology clinical application, and breeding techniques of the Chinese herbal medicine Fritillaria unibracteata. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1428037"},{"key":"ref_36","first-page":"99","article-title":"Cyasterone inhibits IL-1\u03b2-mediated apoptosis and inflammation via the NF-\u03baB and MAPK signaling pathways in rat chondrocytes and ameliorates osteoarthritisin vivo","volume":"21","author":"Teng","year":"2023","journal-title":"Chin. J. Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Qu, Z., Zhang, B., Kong, L., Gong, Y., Feng, M., Gao, X., Wang, D., and Yan, L. (2022). Receptor activator of nuclear factor-\u03baB ligand-mediated osteoclastogenesis signaling pathway and related therapeutic natural compounds. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1043975"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.job.2022.11.003","article-title":"An in vitro study of the effects of Phellodendron bark extract and berberine chloride on periodontal pathogenic bacteria in the oral microbiome","volume":"65","author":"Okuda","year":"2023","journal-title":"J. Oral Biosci."},{"key":"ref_39","first-page":"31","article-title":"Antimicrobial efficacy of 1% chitosan gel against periodontal pathogens: An in vitro study","volume":"12","author":"Sarkar","year":"2020","journal-title":"CODS-J. Dent."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"139504","DOI":"10.1016\/j.ijbiomac.2025.139504","article-title":"Chitosan-based dental barrier membrane for periodontal guided tissue regeneration and guided bone regeneration: A review","volume":"295","author":"Bee","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chang, Z.P., Deng, G.F., Shao, Y.Y., Xu, D., Zhao, Y.N., Sun, Y.F., Zhang, S.Q., Hou, R.G., and Liu, J.J. (2021). Shaoyao-gancao decoction ameliorates the inflammation state in polycystic ovary syndrome rats via remodeling gut microbiota and suppressing the TLR4\/NF-\u03baB pathway. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.670054"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8501","DOI":"10.18632\/aging.204990","article-title":"Xuebijing injection protects sepsis induced myocardial injury by mediating TLR4\/NF-\u03baB\/IKK\u03b1 and JAK2\/STAT3 signaling pathways","volume":"15","author":"Kang","year":"2023","journal-title":"Aging"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Liu, T., Ou, G., Wu, J., Wang, S., Wang, H., Wu, Z., Jiang, Y., Chen, Y., Xu, H., and Deng, L. (2025). Pingwei powder alleviates high-fat diet-induced colonic inflammation by modulating microbial metabolites SCFAs. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1628488"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"156471","DOI":"10.1016\/j.phymed.2025.156471","article-title":"Guizhi Shaoyao Zhimu Decoction alleviates rheumatoid arthritis by inhibiting inflammation by targeting SLPI","volume":"139","author":"Pan","year":"2025","journal-title":"Phytomedicine"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/767\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:16:11Z","timestamp":1776399371000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["medicina62040767"],"URL":"https:\/\/doi.org\/10.3390\/medicina62040767","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]}}}