Investigating the molecular mechanism of epimedium herb in treating rheumatoid arthritis through network pharmacology, molecular docking, and experimental validation.
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| Název: | Investigating the molecular mechanism of epimedium herb in treating rheumatoid arthritis through network pharmacology, molecular docking, and experimental validation. |
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| Autoři: | Ding C; Department of Pharmacy, Wuxi Ninth People's Hospital Affiliated to Soochow University, No. 999 Liang Xi Road, Binhu District, Wuxi, 214000, Jiangsu, China., Liu Q; Department of Clinical Laboratory, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, 214000, Jiangsu, China., You X; Department of Pharmacy, Wuxi Ninth People's Hospital Affiliated to Soochow University, No. 999 Liang Xi Road, Binhu District, Wuxi, 214000, Jiangsu, China., Yuan J; Department of Clinical Laboratory, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, 214000, Jiangsu, China., Xia J; Department of Clinical Laboratory, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, 214000, Jiangsu, China., Tan Y; Department of Clinical Laboratory, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, 214000, Jiangsu, China., Hu Y; Department of Rheumatology and Immunology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214000, Jiangsu, China. hyxtjl@163.com., Wang Q; Department of Clinical Laboratory, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, 214000, Jiangsu, China. wangqiubo2020@suda.edu.cn. |
| Zdroj: | Molecular diversity [Mol Divers] 2025 Oct; Vol. 29 (5), pp. 4061-4081. Date of Electronic Publication: 2025 Jan 16. |
| Způsob vydávání: | Journal Article |
| Jazyk: | English |
| Informace o časopise: | Publisher: ESCOM Science Publishers Country of Publication: Netherlands NLM ID: 9516534 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-501X (Electronic) Linking ISSN: 13811991 NLM ISO Abbreviation: Mol Divers Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Leiden, The Netherlands : ESCOM Science Publishers, c1995- |
| Výrazy ze slovníku MeSH: | Epimedium*/chemistry , Arthritis, Rheumatoid*/drug therapy , Arthritis, Rheumatoid*/metabolism , Arthritis, Rheumatoid*/pathology , Molecular Docking Simulation* , Network Pharmacology* , Drugs, Chinese Herbal*/pharmacology , Drugs, Chinese Herbal*/chemistry, Animals ; Mice ; Synoviocytes/drug effects ; Synoviocytes/metabolism ; Arthritis, Experimental/drug therapy ; Arthritis, Experimental/pathology ; Apoptosis/drug effects ; Humans ; Mice, Inbred DBA ; Male |
| Abstrakt: | Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: This study adhered to the principles of the Declaration of Helsinki and the relevant guidelines and regulations. This study was conducted with the informed consent of patients and received approval from Wuxi Ninth People's Hospital Affiliated to Soochow University Medical Ethical Committee (No. LW20220056). The animal experiments were approved by the Lab Animal Ethical Committee of Wuxi Ninth People's Hospital Affiliated to Soochow University (No. KS2023043). This study attempted to explore the molecular mechanism of Epimedium herb (EH) on rheumatoid arthritis (RA) treatment. We employed network pharmacology, molecular docking, and HPLC analysis to investigate the molecular mechanisms underlying the efficacy of EH in treating RA. To assess the efficacy of EH intervention, RA fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) mouse models were utilized. Ultimately, the active compounds icariin, luteolin, quercetin, and kaempferol were identified, with interleukin-1β (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) emerging as key targets of EH for RA. These targets were found to be downregulated in both in vitro and in vivo experiments following EH intervention. Furthermore, EH treatment induced apoptosis, reduced metastasis and invasion in RA-FLS, and ameliorated arthritis-related symptoms while regulating Th17 and Treg cells in CIA mice. (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.) |
| References: | Cush JJ (2021) Rheumatoid arthritis: early diagnosis and treatment. Med Clin North Am 105(2):355–365. https://doi.org/10.1016/j.mcna.2020.10.006. (PMID: 10.1016/j.mcna.2020.10.00633589108) Alivernini S, Firestein GS, McInnes IB (2022) The pathogenesis of rheumatoid arthritis. Immunity 55(12):2255–2270. https://doi.org/10.1016/j.immuni.2022.11.009. (PMID: 10.1016/j.immuni.2022.11.00936516818) Edilova MI, Akram A, Abdul-Sater AA (2021) Innate immunity drives pathogenesis of rheumatoid arthritis. Biomed J 44(2):172–182. https://doi.org/10.1016/j.bj.2020.06.010. (PMID: 10.1016/j.bj.2020.06.01032798211) Finckh A, Gilbert B, Hodkinson B, Bae SC, Thomas R, Deane KD et al (2022) Global epidemiology of rheumatoid arthritis. Nat Rev Rheumatol 18(10):591–602. https://doi.org/10.1038/s41584-022-00827-y. (PMID: 10.1038/s41584-022-00827-y36068354) Aletaha D, Smolen JS (2018) Diagnosis and management of rheumatoid arthritis: a review. JAMA 320(13):1360–1372. https://doi.org/10.1001/jama.2018.13103. (PMID: 10.1001/jama.2018.1310330285183) Cho WK, Weeratunga P, Lee BH, Park JS, Kim CJ, Ma JY et al (2015) Epimedium koreanum Nakai displays broad spectrum of antiviral activity in vitro and in vivo by inducing cellular antiviral state. Viruses 7(1):352–377. https://doi.org/10.3390/v7010352. (PMID: 10.3390/v7010352256093074306843) Irfan M, Kwon TH, Lee DH, Hong SB, Oh JW, Kim SD et al (2021) Antiplatelet and antithrombotic effects of Epimedium koreanum Nakai. Evid Based Complement Alternat Med 2021:7071987. https://doi.org/10.1155/2021/7071987. (PMID: 10.1155/2021/7071987339537888068545) Jung JY, Park SM, Ko HL, Lee JR, Park CA, Byun SH et al (2018) Epimedium koreanum ameliorates oxidative stress-mediated liver injury by activating nuclear factor erythroid 2-related factor 2. Am J Chin Med 46(2):469–488. https://doi.org/10.1142/S0192415X18500246. (PMID: 10.1142/S0192415X1850024629433393) Qian HQ, Wu DC, Li CY, Liu XR, Han XK, Peng Y et al (2024) A systematic review of traditional uses, phytochemistry, pharmacology and toxicity of Epimedium koreanum Nakai. J Ethnopharmacol 318(Pt B):116957. https://doi.org/10.1016/j.jep.2023.116957. (PMID: 10.1016/j.jep.2023.11695737544344) Lili C, Chunfang X, Hongxia Y, Shouhong G, Zhipeng W, Xia T (2021) Research progress of clinical application of Kunxian capsule. World Chin Med 16(11):1754–1758. Liu T, Zhao M, Zhang Y, Qiu Z, Zhang Y, Zhao C et al (2021) Pharmacokinetic-pharmacodynamic modeling analysis and anti-inflammatory effect of Wangbi capsule in the treatment of adjuvant-induced arthritis. Biomed Chromatogr 35(7):e5101. https://doi.org/10.1002/bmc.5101. (PMID: 10.1002/bmc.510133625739) Wang X, Cao Y, Xu T, Cao W (2021) A meta-analysis of the clinical effect of Kunxian capsule combined with methotrexate or single use in the treatment of rheumatoid arthritis. World J Integr Traditional Western Med 16(2):254–63. https://doi.org/10.13935/j.cnki.sjzx.210212 . Wu J, Su L, Fang Q, Wang W, Su X, Wang Y et al. (2023) Wangbi Capsule for active rheumatoid arthritis: a multicenter, randomized, double-blind, parallel-controlled study. Chin J Integr Traditional Western Med 42(6). https://doi.org/10.7661/j.cjim.20231106.338 . Zhang R, Zhu X, Bai H, Ning K (2019) Network pharmacology databases for traditional chinese medicine: review and assessment. Front Pharmacol 10:123. https://doi.org/10.3389/fphar.2019.00123. (PMID: 10.3389/fphar.2019.00123308469396393382) Zhou Z, Chen B, Chen S, Lin M, Chen Y, Jin S et al (2020) Applications of network pharmacology in traditional Chinese Medicine Research. Evid Based Complement Alternat Med 2020:1646905. https://doi.org/10.1155/2020/1646905. (PMID: 10.1155/2020/1646905321485337042531) Ru J, Li P, Wang J, Zhou W, Li B, Huang C et al (2014) TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 6:13. https://doi.org/10.1186/1758-2946-6-13. (PMID: 10.1186/1758-2946-6-13247356184001360) Guo Y, Walsh AM, Fearon U, Smith MD, Wechalekar MD, Yin X et al (2017) CD40L-dependent pathway is active at various stages of rheumatoid arthritis disease progression. J Immunol 198(11):4490–4501. https://doi.org/10.4049/jimmunol.1601988. (PMID: 10.4049/jimmunol.160198828455435) Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M et al (2013) NCBI GEO: archive for functional genomics data sets-update. Nucleic Acids Res 41(Database issue):D991–D995. https://doi.org/10.1093/nar/gks1193 . Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC et al (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4(5):P3. (PMID: 10.1186/gb-2003-4-5-p312734009) Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (2017) KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 45(D1):D353–D361. https://doi.org/10.1093/nar/gkw1092. (PMID: 10.1093/nar/gkw109227899662) Chen J, Ye W (2024) Molecular mechanisms underlying Tao-Hong-Si-Wu decoction treating hyperpigmentation based on network pharmacology, Mendelian randomization analysis, and experimental verification. Pharm Biol 62(1):296–313. https://doi.org/10.1080/13880209.2024.2330609. (PMID: 10.1080/13880209.2024.23306093855586011632782) Cho WK, Ma JY (2022) Antiviral activity of Epimedium koreanum Nakai water extract against influenza viruses. Biomed Pharmacother 146:112581. https://doi.org/10.1016/j.biopha.2021.112581. (PMID: 10.1016/j.biopha.2021.11258134965505) Liu Y, Grimm M, Dai WT, Hou MC, Xiao ZX, Cao Y (2020) CB-Dock: a web server for cavity detection-guided protein-ligand blind docking. Acta Pharmacol Sin 41(1):138–144. https://doi.org/10.1038/s41401-019-0228-6. (PMID: 10.1038/s41401-019-0228-631263275) Rosengren S, Boyle DL, Firestein GS (2007) Acquisition, culture, and phenotyping of synovial fibroblasts. Methods Mol Med 135:365–375. https://doi.org/10.1007/978-1-59745-401-8_24. (PMID: 10.1007/978-1-59745-401-8_2417951672) Brand DD, Latham KA, Rosloniec EF (2007) Collagen-induced arthritis. Nat Protoc 2(5):1269–1275. https://doi.org/10.1038/nprot.2007.173. (PMID: 10.1038/nprot.2007.17317546023) Li JM, Deng HS, Yao YD, Wang WT, Hu JQ, Dong Y et al (2023) Sinomenine ameliorates collagen-induced arthritis in mice by targeting GBP5 and regulating the P2X7 receptor to suppress NLRP3-related signaling pathways. Acta Pharmacol Sin 44(12):2504–2524. https://doi.org/10.1038/s41401-023-01124-4. (PMID: 10.1038/s41401-023-01124-43748257010692212) Zhao H, Zhao T, Yang J, Huang Q, Wu H, Pan Y et al (2022) Epimedium protects against dyszoospermia in mice with Pex3 knockout by exerting antioxidant effects and regulating the expression level of P16. Cell Death Dis 13(1):69. https://doi.org/10.1038/s41419-021-04435-8. (PMID: 10.1038/s41419-021-04435-8350584298776794) Shi L, Zhao Y, Feng C, Miao F, Dong L, Wang T et al (2022) Therapeutic effects of shaogan fuzi decoction in rheumatoid arthritis: network pharmacology and experimental validation. Front Pharmacol 13:967164. https://doi.org/10.3389/fphar.2022.967164. (PMID: 10.3389/fphar.2022.967164360599439428562) Shen P, Lin W, Ba X, Huang Y, Chen Z, Han L et al (2021) Quercetin-mediated SIRT1 activation attenuates collagen-induced mice arthritis. J Ethnopharmacol 279:114213. https://doi.org/10.1016/j.jep.2021.114213. (PMID: 10.1016/j.jep.2021.11421334023442) Kyrylkova K, Kyryachenko S, Leid M, Kioussi C (2012) Detection of apoptosis by TUNEL assay. Methods Mol Biol 887:41–47. https://doi.org/10.1007/978-1-61779-860-3_5. (PMID: 10.1007/978-1-61779-860-3_522566045) Zhou D, Zhang H, Xue X, Tao Y, Wang S, Ren X et al (2021) Safety evaluation of natural drugs in chronic skeletal disorders: a literature review of clinical trials in the past 20 years. Front Pharmacol 12:801287. https://doi.org/10.3389/fphar.2021.801287. (PMID: 10.3389/fphar.2021.80128735095508) Zhai YK, Guo X, Pan YL, Niu YB, Li CR, Wu XL et al (2013) A systematic review of the efficacy and pharmacological profile of Herba Epimedii in osteoporosis therapy. Pharmazie 68(9):713–722. (PMID: 24147339) Chi L, Gao W, Shu X, Lu X (2014) A natural flavonoid glucoside, icariin, regulates Th17 and alleviates rheumatoid arthritis in a murine model. Mediators Inflamm 2014:392062. https://doi.org/10.1155/2014/392062. (PMID: 10.1155/2014/392062253744434211316) Pu L, Meng Q, Li S, Liu B, Li F (2021) Icariin arrests cell cycle progression and induces cell apoptosis through the mitochondrial pathway in human fibroblast-like synoviocytes. Eur J Pharmacol 912:174585. https://doi.org/10.1016/j.ejphar.2021.174585. (PMID: 10.1016/j.ejphar.2021.17458534678240) Wei CC, Ping DQ, You FT, Qiang CY, Tao C (2016) Icariin prevents cartilage and bone degradation in experimental models of arthritis. Mediators Inflamm 2016:9529630. https://doi.org/10.1155/2016/9529630. (PMID: 10.1155/2016/952963027199510) Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB et al (2021) The role of tumor necrosis factor alpha (TNF-alpha) in autoimmune disease and current TNF-alpha Inhibitors in therapeutics. Int J Mol Sci 22(5). https://doi.org/10.3390/ijms22052719 . Leone GM, Mangano K, Petralia MC, Nicoletti F, Fagone P (2023) Past, present and (Foreseeable) future of biological anti-TNF alpha therapy. J Clin Med 12(4). https://doi.org/10.3390/jcm12041630 . Mahmoud DE, Kaabachi W, Sassi N, Tarhouni L, Rekik S, Jemmali S et al (2022) The synovial fluid fibroblast-like synoviocyte: a long-neglected piece in the puzzle of rheumatoid arthritis pathogenesis. Front Immunol 13:942417. https://doi.org/10.3389/fimmu.2022.942417. (PMID: 10.3389/fimmu.2022.942417359906939388825) Zhao J, Jiang P, Guo S, Schrodi SJ, He D (2021) Apoptosis, autophagy, NETosis, necroptosis, and pyroptosis mediated programmed cell death as targets for innovative therapy in rheumatoid arthritis. Front Immunol 12:809806. https://doi.org/10.3389/fimmu.2021.809806. (PMID: 10.3389/fimmu.2021.809806350031398739882) Taams LS (2020) Interleukin-17 in rheumatoid arthritis: trials and tribulations. J Exp Med 217(3). https://doi.org/10.1084/jem.20192048 . Toghi M, Bitarafan S, Ghafouri-Fard S (2023) Pathogenic Th17 cells in autoimmunity with regard to rheumatoid arthritis. Pathol Res Pract 250:154818. https://doi.org/10.1016/j.prp.2023.154818. (PMID: 10.1016/j.prp.2023.15481837729783) Levescot A, Chang MH, Schnell J, Nelson-Maney N, Yan J, Martinez-Bonet M et al (2021) IL-1beta-driven osteoclastogenic Tregs accelerate bone erosion in arthritis. J Clin Invest 131(18). https://doi.org/10.1172/JCI141008 . Ridgley LA, Anderson AE, Maney NJ, Naamane N, Skelton AJ, Lawson CA et al (2019) IL-6 mediated transcriptional programming of naive CD4+ T cells in early rheumatoid arthritis drives dysregulated effector function. Front Immunol 10:1535. https://doi.org/10.3389/fimmu.2019.01535. (PMID: 10.3389/fimmu.2019.01535313336666618050) Fassio A, Adami G, Gatti D, Orsolini G, Giollo A, Idolazzi L et al (2019) Inhibition of tumor necrosis factor-alpha (TNF-alpha) in patients with early rheumatoid arthritis results in acute changes of bone modulators. Int Immunopharmacol 67:487–489. https://doi.org/10.1016/j.intimp.2018.12.050. (PMID: 10.1016/j.intimp.2018.12.05030599401) Takai S, Jin D (2022) Pathophysiological role of chymase-activated matrix metalloproteinase-9. Biomedicines 10(10). https://doi.org/10.3390/biomedicines10102499 . Wu ZM, Xiang YR, Zhu XB, Shi XD, Chen S, Wan X et al (2022) Icariin represses the inflammatory responses and survival of rheumatoid arthritis fibroblast-like synoviocytes by regulating the TRIB1/TLR2/NF-kB pathway. Int Immunopharmacol 110:108991. https://doi.org/10.1016/j.intimp.2022.108991. (PMID: 10.1016/j.intimp.2022.10899135792272) Liu X, Tao T, Yao H, Zheng H, Wang F, Gao Y (2023) Mechanism of action of quercetin in rheumatoid arthritis models: meta-analysis and systematic review of animal studies. Inflammopharmacology 31(4):1629–1645. https://doi.org/10.1007/s10787-023-01196-y. (PMID: 10.1007/s10787-023-01196-y37150762) Pan D, Li N, Liu Y, Xu Q, Liu Q, You Y et al (2018) Kaempferol inhibits the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes by blocking activation of the MAPK pathway. Int Immunopharmacol 55:174–182. https://doi.org/10.1016/j.intimp.2017.12.011. (PMID: 10.1016/j.intimp.2017.12.01129268189) Xiao B, Li J, Qiao Z, Yang S, Kwan HY, Jiang T, et al. (2023) Therapeutic effects of Siegesbeckia orientalis L. and its active compound luteolin in rheumatoid arthritis: network pharmacology, molecular docking and experimental validation. J Ethnopharmacol 317:116852. https://doi.org/10.1016/j.jep.2023.116852 . Li SL, Gao H, Zhang KH (2008) Effects of Epimedium on proliferation, function and apoptosis of mouse osteoblasts in vitro. Beijing Da Xue Xue Bao Yi Xue Ban 40(1):43–46. (PMID: 18278136) Song YH, Li BS, Chen XM, Cai H (2008) Ethanol extract from Epimedium brevicornum attenuates left ventricular dysfunction and cardiac remodeling through down-regulating matrix metalloproteinase-2 and -9 activity and myocardial apoptosis in rats with congestive heart failure. Int J Mol Med 21(1):117–124. (PMID: 18097624) Lee W, Nam JH, Cho HJ, Lee JY, Cho WK, Kim U et al (2017) Epimedium koreanum Nakai inhibits PMA-induced cancer cell migration and invasion by modulating NF-kappaB/MMP-9 signaling in monomorphic malignant human glioma cells. Oncol Rep 38(6):3619–3631. https://doi.org/10.3892/or.2017.6043. (PMID: 10.3892/or.2017.604329130110) Wu Z, Liu Q, Cao Z, Li H, Zhou Y, Zhang P (2024) Icariin decreases cell proliferation and inflammation of rheumatoid arthritis-fibroblast like synoviocytes via GAREM1/MAPK signaling pathway. Immunopharmacol Immunotoxicol 46(1):86–92. https://doi.org/10.1080/08923973.2023.2253990. (PMID: 10.1080/08923973.2023.225399037647355) Zheng W, Wang H, Wang X, Li X, Hu J, Zi X, et al. (2024) Kaempferol 3-O-Rutinoside, a flavone derived from Tetrastigma hemsleyanum Diels et Gilg, reduces body temperature through accelerating the elimination of IL-6 and TNF-alpha in a mouse fever model. Molecules 29(7). https://doi.org/10.3390/molecules29071641 . Zhou W, Hu M, Hu J, Du Z, Su Q, Xiang Z (2021) Luteolin suppresses microglia neuroinflammatory responses and relieves inflammation-induced cognitive impairments. Neurotox Res 39(6):1800–1811. https://doi.org/10.1007/s12640-021-00426-x. (PMID: 10.1007/s12640-021-00426-x34655374) Rosloniec EF, Whittington K, Proslovsky A, Brand DD (2021) Collagen-induced arthritis mouse model. Curr Protoc 1(12):e313. https://doi.org/10.1002/cpz1.313. (PMID: 10.1002/cpz1.31334890495) Sun P, Liu Y, Deng X, Yu C, Dai N, Yuan X et al (2013) An inhibitor of cathepsin K, icariin suppresses cartilage and bone degradation in mice of collagen-induced arthritis. Phytomedicine 20(11):975–979. https://doi.org/10.1016/j.phymed.2013.04.019. (PMID: 10.1016/j.phymed.2013.04.01923746958) Lee CJ, Moon SJ, Jeong JH, Lee S, Lee MH, Yoo SM et al (2018) Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis. Cell Death Dis 9(3):401. https://doi.org/10.1038/s41419-018-0433-0. (PMID: 10.1038/s41419-018-0433-0295406975851988) Paradowska-Gorycka A, Wajda A, Romanowska-Prochnicka K, Walczuk E, Kuca-Warnawin E, Kmiolek T et al (2020) Th17/Treg-related transcriptional factor expression and cytokine profile in patients with rheumatoid arthritis. Front Immunol 11:572858. https://doi.org/10.3389/fimmu.2020.572858. (PMID: 10.3389/fimmu.2020.572858333627617759671) Zhang L, Zhang YD, Jiang M (2021) Effect and mechanism of epimedium polysaccharide on bone marrow hematopoietic function and Th17/Treg balance in aplastic anemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi 29(5):1548–1554. https://doi.org/10.19746/j.cnki.issn.1009-2137.2021.05.027 . |
| Grant Information: | Q202237 Scientific Research Project of Wuxi Municipal Health Commission; H2023093 Scientific Research Program of Jiangsu Health Commission; BJ2023109 Top Talent Support Program for young and middle-aged people of Wuxi Health Committee; JSYGY-3-2024-94 Jiangsu Provincial Hospital Association hospital management innovation research project; x202319 Jiangsu Provincial Health Commission parasite prevention and control research project |
| Contributed Indexing: | Keywords: Collagen-induced arthritis; Epimedium herb; Fibroblast-like synoviocytes; Network pharmacology; Rheumatoid arthritis |
| Substance Nomenclature: | 0 (Drugs, Chinese Herbal) |
| Entry Date(s): | Date Created: 20250117 Date Completed: 20250922 Latest Revision: 20250922 |
| Update Code: | 20250923 |
| DOI: | 10.1007/s11030-024-11019-z |
| PMID: | 39821498 |
| Databáze: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: This study adhered to the principles of the Declaration of Helsinki and the relevant guidelines and regulations. This study was conducted with the informed consent of patients and received approval from Wuxi Ninth People's Hospital Affiliated to Soochow University Medical Ethical Committee (No. LW20220056). The animal experiments were approved by the Lab Animal Ethical Committee of Wuxi Ninth People's Hospital Affiliated to Soochow University (No. KS2023043).<br />This study attempted to explore the molecular mechanism of Epimedium herb (EH) on rheumatoid arthritis (RA) treatment. We employed network pharmacology, molecular docking, and HPLC analysis to investigate the molecular mechanisms underlying the efficacy of EH in treating RA. To assess the efficacy of EH intervention, RA fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) mouse models were utilized. Ultimately, the active compounds icariin, luteolin, quercetin, and kaempferol were identified, with interleukin-1β (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) emerging as key targets of EH for RA. These targets were found to be downregulated in both in vitro and in vivo experiments following EH intervention. Furthermore, EH treatment induced apoptosis, reduced metastasis and invasion in RA-FLS, and ameliorated arthritis-related symptoms while regulating Th17 and Treg cells in CIA mice.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.) |
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| ISSN: | 1573-501X |
| DOI: | 10.1007/s11030-024-11019-z |