{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T09:29:36Z","timestamp":1773912576731,"version":"3.50.1"},"reference-count":93,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan","award":["TCRD-TPE-111-06 (2\/2)"],"award-info":[{"award-number":["TCRD-TPE-111-06 (2\/2)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation, joint destruction, and systemic complications. The nucleotide-binding domain, leucine-rich repeat family, pyrin domain-containing-3 (NLRP3) inflammasome plays a pivotal role in RA pathogenesis by driving the release of pro-inflammatory cytokines and exacerbating oxidative stress. Recent studies identified methyl canthin-6-one-2-carboxylate (Cant) as a potential therapeutic agent that modulates the NLRP3 inflammasome pathway. This review explores the mechanistic role of Cant in RA treatment, particularly its effect on oxidative stress, synovial macrophages, and inflammatory signaling pathways. Additionally, we discuss alternative and complementary approaches, such as gut microbiota modulation and mesenchymal stem cell-based therapies, in the management of RA. Although preliminary findings suggest that Cant exhibits promising anti-inflammatory effects, further preclinical and clinical studies are necessary to validate its therapeutic efficacy. Future research should focus on optimizing dosage, exploring combination therapies, and elucidating the broader implications of targeting the NLRP3 inflammasome for RA treatment.<\/jats:p>","DOI":"10.3390\/cimb47040254","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T20:43:17Z","timestamp":1745440997000},"page":"254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of Methyl Canthin-6-one-2-carboxylate in Targeting the NLRP3 Inflammasome in Rheumatoid Arthritis Treatment"],"prefix":"10.3390","volume":"47","author":[{"given":"Chung-Che","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1795-7924","authenticated-orcid":false,"given":"Tin-Yi","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Chih","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"},{"name":"Institute of Oral Medicine and Materials, College of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5702-5730","authenticated-orcid":false,"given":"Chan-Yen","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"},{"name":"Institute of Oral Medicine and Materials, College of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chen, Y., Zhang, Z., Yao, Y., Zhou, X., Ling, Y., Mao, L., and Gu, Z. (2025). Methyl Canthin-6-one-2-carboxylate Inhibits the Activation of the NLRP3 Inflammasome in Synovial Macrophages by Upregulating Nrf2 Expression. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47010038"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31215","DOI":"10.1021\/acsomega.3c03358","article-title":"Novel Canthin-6-one Derivatives: Design, Synthesis, and Their Antiproliferative Activities via Inducing Apoptosis, Deoxyribonucleic Acid Damage, and Ferroptosis","volume":"8","author":"Ding","year":"2023","journal-title":"ACS Omega"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gao, Y., Zhang, Y., and Liu, X. (2024). Rheumatoid arthritis: Pathogenesis and therapeutic advances. MedComm, 5.","DOI":"10.1002\/mco2.509"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Blevins, H.M., Xu, Y., Biby, S., and Zhang, S. (2022). The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.879021"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rosa, C.P., Belo, T.C.A., Santos, N.C.M., Silva, E.N., Gasparotto, J., Corsetti, P.P., and de Almeida, L.A. (2023). Reactive oxygen species trigger inflammasome activation after intracellular microbial interaction. Life Sci., 331.","DOI":"10.1016\/j.lfs.2023.122076"},{"key":"ref_6","first-page":"2092","article-title":"Nrf2 as a regulator of energy metabolism and mitochondrial function","volume":"598","author":"Luchkova","year":"2024","journal-title":"FEBS Lett."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ding, Q., Hu, W., Wang, R., Yang, Q., Zhu, M., Li, M., Cai, J., Rose, P., Mao, J., and Zhu, Y.Z. (2023). Signaling pathways in rheumatoid arthritis: Implications for targeted therapy. Signal Transduct. Target. Ther., 8.","DOI":"10.1038\/s41392-023-01331-9"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Liao, H., Zheng, J., Lu, J., and Shen, H.L. (2024). NF-kappaB Signaling Pathway in Rheumatoid Arthritis: Mechanisms and Therapeutic Potential. Mol. Neurobiol., online ahead of print.","DOI":"10.1007\/s12035-024-04634-2"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.7150\/jca.71401","article-title":"Role and mechanism of miR-211 in human cancer","volume":"13","author":"Ye","year":"2022","journal-title":"J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cheng, L., and Rong, X. (2025). Clinical application of biological agents in rheumatoid arthritis. Transpl. Immunol., 89.","DOI":"10.1016\/j.trim.2025.102187"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, Z., Guo, J., and Bi, L. (2020). Role of the NLRP3 inflammasome in autoimmune diseases. Biomed. Pharmacother., 130.","DOI":"10.1016\/j.biopha.2020.110542"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Wang, Y., Xu, Q., Zhou, X., Ling, Y., Zhang, J., and Mao, L. (2023). Methyl Canthin-6-one-2-carboxylate Restrains the Migration\/Invasion Properties of Fibroblast-like Synoviocytes by Suppressing the Hippo\/YAP Signaling Pathway. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101440"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/ptr.2136","article-title":"Antibacterial activity of two canthin-6-one alkaloids from Allium neapolitanum","volume":"21","author":"Gibbons","year":"2007","journal-title":"Phytother. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yin, H., Liu, N., Sigdel, K.R., and Duan, L. (2022). Role of NLRP3 Inflammasome in Rheumatoid Arthritis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.931690"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1038\/s41423-020-00630-3","article-title":"Necroptosis, pyroptosis and apoptosis: An intricate game of cell death","volume":"18","author":"Bertheloot","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, Y., Ye, X., Escames, G., Lei, W., Zhang, X., Li, M., Jing, T., Yao, Y., Qiu, Z., and Wang, Z. (2023). The NLRP3 inflammasome: Contributions to inflammation-related diseases. Cell. Mol. Biol. Lett., 28.","DOI":"10.1186\/s11658-023-00462-9"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Huang, W., Zhang, Z., Qiu, Y., Gao, Y., Fan, Y., Wang, Q., and Zhou, Q. (2023). NLRP3 inflammasome activation in response to metals. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1055788"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xu, Z., Kombe Kombe, A.J., Deng, S., Zhang, H., Wu, S., Ruan, J., Zhou, Y., and Jin, T. (2024). NLRP inflammasomes in health and disease. Mol. Biomed., 5.","DOI":"10.1186\/s43556-024-00179-x"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.gendis.2023.01.009","article-title":"Fantastic voyage: The journey of NLRP3 inflammasome activation","volume":"11","author":"Que","year":"2024","journal-title":"Genes Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Xiao, Y., and Zhang, L. (2023). Mechanistic and therapeutic insights into the function of NLRP3 inflammasome in sterile arthritis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1273174"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Liu, J., Han, X., Zhang, T., Tian, K., Li, Z., and Luo, F. (2023). Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: From mechanism to therapy. J. Hematol. Oncol., 16.","DOI":"10.1186\/s13045-023-01512-7"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Koziel, J., Mydel, P., and Potempa, J. (2014). The link between periodontal disease and rheumatoid arthritis: An updated review. Curr. Rheumatol. Rep., 16.","DOI":"10.1007\/s11926-014-0408-9"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1136\/annrheumdis-2018-213697","article-title":"Porphyromonas gingivalis experimentally induces periodontis and an anti-CCP2-associated arthritis in the rat","volume":"78","author":"Courbon","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Febles, J., Rodr\u00edguez-Lozano, B., S\u00e1nchez-Piedra, C., Garnier-Rodr\u00edguez, J., Bustabad, S., Hern\u00e1ndez-Gonz\u00e1lez, M., Gonz\u00e1lez-D\u00e1vila, E., Sanz, M., and D\u00edaz-Gonz\u00e1lez, F. (2020). Association between periodontitis and anti-citrullinated protein antibodies in rheumatoid arthritis patients: A cross-sectional study. Arthritis Res. Ther., 22.","DOI":"10.1186\/s13075-020-2121-6"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/art.38348","article-title":"Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis","volume":"66","author":"Mikuls","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1902\/jop.2011.100481","article-title":"Clinical periodontal and microbiologic parameters in patients with rheumatoid arthritis","volume":"82","author":"Ziebolz","year":"2011","journal-title":"J. Periodontol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1600-051X.2012.01885.x","article-title":"The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation","volume":"39","author":"Nesse","year":"2012","journal-title":"J. Clin. Periodontol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"M\u00fcnzer, P., Negro, R., Fukui, S., di Meglio, L., Aymonnier, K., Chu, L., Cherpokova, D., Gutch, S., Sorvillo, N., and Shi, L. (2021). NLRP3 Inflammasome Assembly in Neutrophils Is Supported by PAD4 and Promotes NETosis Under Sterile Conditions. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.683803"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wu, J., Chen, X., Lv, Y., Gao, K., Liu, Z., Zhao, Y., Chen, X., He, X., Chu, Y., and Wu, X. (2020). Chinese Herbal Formula Huayu-Qiangshen-Tongbi Decoction Compared With Leflunomide in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis: An Open-Label, Randomized, Controlled, Pilot Study. Front. Med., 7.","DOI":"10.3389\/fmed.2020.00484"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Shah, D.K., Ghosh, S., More, N., Choppadandi, M., Sinha, M., Srivalliputtur, S.B., Velayutham, R., and Kapusetti, G. (2024). ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment. BMC Biotechnol., 24.","DOI":"10.1186\/s12896-024-00856-3"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/joim.13537","article-title":"Where traditional Chinese medicine meets Western medicine in the prevention of rheumatoid arthritis","volume":"292","author":"Jakobsson","year":"2022","journal-title":"J. Intern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, Z., Wu, J., Li, D., Tang, X., Zhao, Y., Cai, X., Chen, X., Chen, X., Huang, Q., and Huang, R. (2020). Traditional Chinese medicine Biqi capsule compared with leflunomide in combination with methotrexate in patients with rheumatoid arthritis: A randomized controlled trial. Chin. Med., 15.","DOI":"10.1186\/s13020-020-00319-9"},{"key":"ref_33","first-page":"5221","article-title":"Systematic review and meta-analysis of the efficacy and safety of Biqi capsule in rheumatoid arthritis patients","volume":"15","author":"Chen","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jep.2015.10.024","article-title":"Characteristics of traditional Chinese medicine use in patients with rheumatoid arthritis in Taiwan: A nationwide population-based study","volume":"176","author":"Huang","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, Y., Chen, S., Du, K., Liang, C., Wang, S., Owusu Boadi, E., Li, J., Pang, X., He, J., and Chang, Y.X. (2021). Traditional herbal medicine: Therapeutic potential in rheumatoid arthritis. J. Ethnopharmacol., 279.","DOI":"10.1016\/j.jep.2021.114368"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1007\/s10787-024-01445-8","article-title":"Pathophysiology, diagnosis, and herbal medicine-based therapeutic implication of rheumatoid arthritis: An overview","volume":"32","author":"Kaur","year":"2024","journal-title":"Inflammopharmacology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Jo, H.G., Seo, J., and Lee, D. (2022). Clinical evidence construction of East Asian herbal medicine for inflammatory pain in rheumatoid arthritis based on integrative data mining approach. Pharmacol. Res., 185.","DOI":"10.1016\/j.phrs.2022.106460"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.jtcme.2022.01.005","article-title":"Conventional disease-modifying anti-rheumatic drugs combined with Chinese Herbal Medicines for rheumatoid arthritis: A systematic review and meta-analysis","volume":"12","author":"Han","year":"2022","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Syed Zameer Ahmed, K., Ahmed, S.S.Z., Thangakumar, A., and Krishnaveni, R. (2019). Therapeutic effect of Parmotrema tinctorum against complete Freund\u2019s adjuvant-induced arthritis in rats and identification of novel Isophthalic ester derivative. Biomed. Pharmacother., 112.","DOI":"10.1016\/j.biopha.2019.108646"},{"key":"ref_40","first-page":"301","article-title":"Control of autoimmune arthritis by herbal extracts and their bioactive components","volume":"11","author":"Venkatesha","year":"2016","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Nanjundaiah, S.M., Lee, D.Y., Ma, Z., Fong, H.H., Lao, L., Berman, B.M., and Moudgil, K.D. (2012). Modified huo-luo-xiao-ling dan suppresses adjuvant arthritis by inhibiting chemokines and matrix-degrading enzymes. Evid. Based Complement. Alternat. Med., 2012.","DOI":"10.1155\/2012\/589256"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tong, L., and Moudgil, K.D. (2007). Celastrus aculeatus Merr. suppresses the induction and progression of autoimmune arthritis by modulating immune response to heat-shock protein 65. Arthritis Res. Ther., 9.","DOI":"10.1186\/ar2268"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/jn\/132.3.341","article-title":"Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilage proteoglycan and type II collagen degradation in vitro","volume":"132","author":"Adcocks","year":"2002","journal-title":"J. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Deligiannidou, G.E., Gougoula, V., Bezirtzoglou, E., Kontogiorgis, C., and Constantinides, T.K. (2021). The Role of Natural Products in Rheumatoid Arthritis: Current Knowledge of Basic In Vitro and In Vivo Research. Antioxidants, 10.","DOI":"10.3390\/antiox10040599"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1093\/rheumatology\/keg183","article-title":"Herbal medicines for the treatment of rheumatoid arthritis: A systematic review","volume":"42","author":"Soeken","year":"2003","journal-title":"Rheumatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ejphar.2016.04.020","article-title":"Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes","volume":"785","author":"Sergeant","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1002\/art.20303","article-title":"Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: A multicenter, double-blind, placebo-controlled trial","volume":"50","author":"Nishimoto","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1002\/art.11181","article-title":"Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis","volume":"48","author":"Cambridge","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0140-6736(08)61000-4","article-title":"Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): A randomised, double-blind, parallel treatment trial","volume":"372","author":"Emery","year":"2008","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s10753-009-9157-8","article-title":"Gamma-linolenic acid inhibits inflammatory responses by regulating NF-kappaB and AP-1 activation in lipopolysaccharide-induced RAW 264.7 macrophages","volume":"33","author":"Chang","year":"2010","journal-title":"Inflammation"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Fu, Y., Zhou, H., Wang, S., and Wei, Q. (2014). Glycyrol suppresses collagen-induced arthritis by regulating autoimmune and inflammatory responses. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098137"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1021\/acs.jafc.9b00185","article-title":"Liquiritin from Glycyrrhiza uralensis Attenuating Rheumatoid Arthritis via Reducing Inflammation, Suppressing Angiogenesis, and Inhibiting MAPK Signaling Pathway","volume":"67","author":"Zhai","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Al-Nahain, A., Jahan, R., and Rahmatullah, M. (2014). Zingiber officinale: A Potential Plant against Rheumatoid Arthritis. Arthritis, 2014.","DOI":"10.1155\/2014\/159089"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lee, W.S., Lim, J.H., Sung, M.S., Lee, E.G., Oh, Y.J., and Yoo, W.H. (2014). Ethyl acetate fraction from Angelica sinensis inhibits IL-1\u03b2-induced rheumatoid synovial fibroblast proliferation and COX-2, PGE2, and MMPs production. Biol. Res., 47.","DOI":"10.1186\/0717-6287-47-41"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"He, D.Y., and Dai, S.M. (2011). Anti-inflammatory and immunomodulatory effects of paeonia lactiflora pall., a traditional chinese herbal medicine. Front. Pharmacol., 2.","DOI":"10.3389\/fphar.2011.00010"},{"key":"ref_56","first-page":"2791","article-title":"Inhibitory effect of Saposhnikovia divaricate polysaccharide on fibroblast-like synoviocytes from rheumatoid arthritis rat in vitro","volume":"31","author":"Ci","year":"2018","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Li, W., Wang, K., Liu, Y., Wu, H., He, Y., Li, C., Wang, Q., Su, X., Yan, S., and Su, W. (2022). A Novel Drug Combination of Mangiferin and Cinnamic Acid Alleviates Rheumatoid Arthritis by Inhibiting TLR4\/NF\u03baB\/NLRP3 Activation-Induced Pyroptosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.912933"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Xia, X., May, B.H., Zhang, A.L., Guo, X., Lu, C., Xue, C.C., and Huang, Q. (2020). Chinese Herbal Medicines for Rheumatoid Arthritis: Text-Mining the Classical Literature for Potentially Effective Natural Products. Evid.-Based Complement. Alternat. Med., 2020.","DOI":"10.1155\/2020\/7531967"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ijbiomac.2016.01.010","article-title":"A pure polysaccharide from Ephedra sinica treating on arthritis and inhibiting cytokines expression","volume":"86","author":"Wang","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Gu, S., Li, L., Huang, H., Wang, B., and Zhang, T. (2019). Antitumor, Antiviral, and Anti-Inflammatory Efficacy of Essential Oils from Atractylodes macrocephala Koidz. Produced with Different Processing Methods. Molecules, 24.","DOI":"10.3390\/molecules24162956"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1055\/s-2005-871231","article-title":"Phthalide Lactones from Ligusticum chuanxiong inhibit lipopolysaccharide-induced TNF-alpha production and TNF-alpha-mediated NF-kappaB Activation","volume":"71","author":"Liu","year":"2005","journal-title":"Planta Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1055\/s-0034-1368196","article-title":"Polyacetylenes from Radix et Rhizoma Notopterygii incisi with an inhibitory effect on nitric oxide production in vitro","volume":"80","author":"Blunder","year":"2014","journal-title":"Planta Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.bioorg.2016.11.012","article-title":"Bioactivity-guided isolation of anti-inflammatory triterpenoids from the sclerotia of Poria cocos using LPS-stimulated Raw264.7 cells","volume":"70","author":"Lee","year":"2017","journal-title":"Bioorg. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhao, T., Wei, Y., Zhu, Y., Xie, Z., Hai, Q., Li, Z., and Qin, D. (2022). Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1007165"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Tsetseri, M.N., Silman, A.J., Keene, D.J., and Dakin, S.G. (2023). The role of the microbiome in rheumatoid arthritis: A review. Rheumatol. Adv. Pract., 7.","DOI":"10.1093\/rap\/rkad034"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lin, L., Zhang, K., Xiong, Q., Zhang, J., Cai, B., Huang, Z., Yang, B., Wei, B., Chen, J., and Niu, Q. (2023). Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression. J. Autoimmun., 141.","DOI":"10.1016\/j.jaut.2023.103001"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Opoku, Y.K., Asare, K.K., Ghartey-Quansah, G., Afrifa, J., Bentsi-Enchill, F., Ofori, E.G., Koomson, C.K., and Kumi-Manu, R. (2022). Intestinal microbiome-rheumatoid arthritis crosstalk: The therapeutic role of probiotics. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.996031"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Ferro, M., Charneca, S., Dourado, E., Guerreiro, C.S., and Fonseca, J.E. (2021). Probiotic Supplementation for Rheumatoid Arthritis: A Promising Adjuvant Therapy in the Gut Microbiome Era. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.711788"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Pang, J., Ma, S., Xu, X., Zhang, B., and Cai, Q. (2021). Effects of rhizome of Atractylodes koreana (Nakai) Kitam on intestinal flora and metabolites in rats with rheumatoid arthritis. J. Ethnopharmacol., 281.","DOI":"10.1016\/j.jep.2021.114026"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/nm.3914","article-title":"The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment","volume":"21","author":"Zhang","year":"2015","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10067-017-3821-4","article-title":"The role of gut microbiota in the pathogenesis of rheumatic diseases","volume":"37","author":"Zhong","year":"2018","journal-title":"Clin. Rheumatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/art.39259","article-title":"Microbiome in Inflammatory Arthritis and Human Rheumatic Diseases","volume":"68","author":"Scher","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Chasov, V., Gilyazova, E., Ganeeva, I., Zmievskaya, E., Davletshin, D., Valiullina, A., and Bulatov, E. (2024). Gut Microbiota Modulation: A Novel Strategy for Rheumatoid Arthritis Therapy. Biomolecules, 14.","DOI":"10.3390\/biom14121653"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Rooney, C.M., Jeffery, I.B., Mankia, K., Wilcox, M.H., and Emery, P. (2024). Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: A cross-sectional and longitudinal observational study. Ann. Rheum. Dis., online ahead of print.","DOI":"10.1136\/ard-2024-226362"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Koh, J.H., Lee, E.H., Cha, K.H., Pan, C.H., Kim, D., and Kim, W.U. (2023). Factors associated with the composition of the gut microbiome in patients with established rheumatoid arthritis and its value for predicting treatment responses. Arthritis Res. Ther., 25.","DOI":"10.1186\/s13075-023-03013-x"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Longo, U.G., Lalli, A., Bandini, B., de Sire, R., Angeletti, S., Lustig, S., Ammendolia, A., Budhiparama, N.C., and de Sire, A. (2024). Role of the Gut Microbiota in Osteoarthritis, Rheumatoid Arthritis, and Spondylarthritis: An Update on the Gut-Joint Axis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063242"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41584-021-00585-3","article-title":"The gut-joint axis in rheumatoid arthritis","volume":"17","author":"Zaiss","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Bungau, S.G., Behl, T., Singh, A., Sehgal, A., Singh, S., Chigurupati, S., Vijayabalan, S., Das, S., and Palanimuthu, V.R. (2021). Targeting Probiotics in Rheumatoid Arthritis. Nutrients, 13.","DOI":"10.3390\/nu13103376"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Liang, Y., Liu, M., Cheng, Y., Wang, X., and Wang, W. (2023). Prevention and treatment of rheumatoid arthritis through traditional Chinese medicine: Role of the gut microbiota. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1233994"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/art.40003","article-title":"Evidence of the Immune Relevance of Prevotella copri, a Gut Microbe, in Patients With Rheumatoid Arthritis","volume":"69","author":"Pianta","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Maeda, Y., and Takeda, K. (2017). Role of Gut Microbiota in Rheumatoid Arthritis. J. Clin. Med., 6.","DOI":"10.3390\/jcm6060060"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Yao, Y., Cai, X., Fei, W., Ren, F., Wang, F., Luan, X., Chen, F., and Zheng, C. (2020). Regulating Gut Microbiome: Therapeutic Strategy for Rheumatoid Arthritis During Pregnancy and Lactation. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.594042"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Xu, Q., Hou, W., Zhao, B., Fan, P., Wang, S., Wang, L., and Gao, J. (2024). Mesenchymal stem cells lineage and their role in disease development. Mol. Med., 30.","DOI":"10.1186\/s10020-024-00967-9"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Babaahmadi, M., Tayebi, B., Gholipour, N.M., Kamardi, M.T., Heidari, S., Baharvand, H., Eslaminejad, M.B., Hajizadeh-Saffar, E., and Hassani, S.N. (2023). Rheumatoid arthritis: The old issue, the new therapeutic approach. Stem Cell. Res. Ther., 14.","DOI":"10.1186\/s13287-023-03473-7"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Sarsenova, M., Issabekova, A., Abisheva, S., Rutskaya-Moroshan, K., Ogay, V., and Saparov, A. (2021). Mesenchymal Stem Cell-Based Therapy for Rheumatoid Arthritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111592"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1136\/annrheumdis-2020-217798","article-title":"Combination of human umbilical cord mesenchymal stem (stromal) cell transplantation with IFN-gamma treatment synergistically improves the clinical outcomes of patients with rheumatoid arthritis","volume":"79","author":"He","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Vij, R., Stebbings, K.A., Kim, H., Park, H., and Chang, D. (2022). Safety and efficacy of autologous, adipose-derived mesenchymal stem cells in patients with rheumatoid arthritis: A phase I\/IIa, open-label, non-randomized pilot trial. Stem Cell Res. Ther., 13.","DOI":"10.1186\/s13287-022-02763-w"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/stcltm\/szad065","article-title":"Therapeutic Effects of Mesenchymal\/Stromal Stem Cells and Their Derived Extracellular Vesicles in Rheumatoid Arthritis","volume":"12","author":"Tsiapalis","year":"2023","journal-title":"Stem Cells Transl. Med."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Mesa, L.E., Lopez, J.G., Lopez Quiceno, L., Barrios Arroyave, F., Halpert, K., and Camacho, J.C. (2023). Safety and efficacy of mesenchymal stem cells therapy in the treatment of rheumatoid arthritis disease: A systematic review and meta-analysis of clinical trials. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0284828"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Sun, Y., Deng, W., Geng, L., Zhang, L., Liu, R., Chen, W., Yao, G., Zhang, H., Feng, X., and Gao, X. (2015). Mesenchymal stem cells from patients with rheumatoid arthritis display impaired function in inhibiting Th17 cells. J. Immunol. Res., 2015.","DOI":"10.1155\/2015\/284215"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.ebiom.2019.08.073","article-title":"Meta-analysis of preclinical studies of mesenchymal stromal cells to treat rheumatoid arthritis","volume":"47","author":"Liu","year":"2019","journal-title":"eBioMedicine"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Alivernini, S., Masserdotti, A., Magatti, M., Cargnoni, A., Papait, A., Silini, A.R., Romoli, J., Ficai, S., Di Mario, C., and Gremese, E. (2025). Exploring perinatal mesenchymal stromal cells as a potential therapeutic strategy for rheumatoid arthritis. Heliyon, 11.","DOI":"10.1016\/j.heliyon.2024.e41438"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1080\/1744666X.2023.2299729","article-title":"A comprehensive review on the role of mesenchymal stromal\/stem cells in the management of rheumatoid arthritis","volume":"20","author":"Pignatti","year":"2024","journal-title":"Expert Rev. Clin. Immunol."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/4\/254\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:11:48Z","timestamp":1760029908000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/4\/254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,7]]},"references-count":93,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["cimb47040254"],"URL":"https:\/\/doi.org\/10.3390\/cimb47040254","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,7]]}}}