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BMC Complementary Medicine and Therapies

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Open Access 01-12-2021 | Rheumatoid Arthritis | Research

Network analysis indicating the pharmacological mechanism of Yunpi-Qufeng-Chushi-prescription in prophylactic treatment of rheumatoid arthritis

Authors: Lin Li, Donghai Zhou, Qiuping Liu, Dianming Li, Qiao Wang, Xiaowei Shi, Chengping Wen, Lin Huang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Abstract

Background

Rheumatoid arthritis (RA), is an autoimmune inflammatory disease with increasing global morbidity and high disability. Early treatment is an effective intervention to slow down joint deformation. However, as for early RA and pre-RA patients, it sometimes takes a long time to make a definite diagnosis and few guidelines have made suggestion for these suspected or early phrase individuals. Yunpi-Qufeng-Chushi-Prescription (YQCP) is an optimization of the traditional formula, Cangzhu Fangfeng Tang which is effective for arthromyodynia management.

Methods

In this study, LC-MS identify the main component of YQCP. Ingredients of the 11 herbs were collected from Traditional Chinese Medicine Integrated Database (TCMID). Targets of these ingredients were collected from two source, TCMID and PharmMapper. Microarray of 20 early untreated RA patients and corresponding health control were download from NCBI Gene Expression Omnibus (GEO) database to defined the differential expressed genes. Gene ontology analysis and KEGG enrichment analysis were carried out for the YQCP. Protein-protein interactions (PPIs) networks were constructed to identify the hub targets. At last, molecular docking (MD) were conducted to further verified the the possibility of YQCP for RA therapy.

Result

The study indicated that by acting on hub targets such as C3, EGFR, SRC and MMP9, YQCP may influence the mature of B cells and inhibit B cell-related IgG production, regulate oxidative stress and modulate activity of several enzymes including peroxidase and metallopeptidase to delay the occurrence and progress of RA and benefit the pre-RA or early RA patients.

Conclusion

YQCP is a potential effective therapy for prophylactic treatment of RA.

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Smith E, Hoy D, Cross M, Merriman TR, Vos T, Buchbinder R, et al. The global burden of gout: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(8):1470–6. https://doi.org/10.1136/annrheumdis-2013-204647.CrossRefPubMed

McInnes IB, Schett G. Mechanisms of disease the pathogenesis of rheumatoid arthritis. New Engl J Med. 2011;365(23):2205–19. https://doi.org/10.1056/NEJMra1004965.CrossRefPubMed

Paulissen SMJ, van Hamburg JP, Dankers W, Lubberts E. The role and modulation of CCR6+Th17 cell populations in rheumatoid arthritis. Cytokine. 2015;74(1):43–53. https://doi.org/10.1016/j.cyto.2015.02.002.CrossRefPubMed

Prodinger B, Ndosi M, Nordenskiold U, Stamm T, Persson G, Andreasson I, et al. Rehabilitation provided to patients with rheumatoid arthritis: a comparison of three different rheumatology clinics in Austria, Sweden and the Uk from the perspectives of patients and health professionals. J Rehabil Med. 2015;47(2):174–82. https://doi.org/10.2340/16501977-1914.CrossRefPubMed

Sun E, Negi A, Davies R. An audit of current clinical practice in the rheumatology Department of University Hospital Wales against the top ten quality standards for rheumatoid arthritis as defined by the British Society for Rheumatology. Rheumatology. 2015;54:103.

Xie CM, Jiang J, Liu JP, Yuan GH, Zhao ZY. Triptolide suppresses human synoviocyte MH7A cells mobility and maintains redox balance by inhibiting autophagy. Biomed Pharmacother. 2019;115:108911. https://doi.org/10.1016/j.biopha.2019.108911.CrossRefPubMed

Wang SL, Liu ZG, Wang JC, Wang YF, Liu JH, Ji XY, et al. The triptolide-induced apoptosis of osteoclast precursor by degradation of cIAP2 and treatment of rheumatoid arthritis of TNF-transgenic mice. Phytother Res. 2019;33(2):342–9. https://doi.org/10.1002/ptr.6224.CrossRefPubMed

Lin H, Donghai Z, Zhixing H, Qiao W, Chengping W. Effect of Yunpi Qufeng Chushi Prescription on CIA Rats. J Zhejiang Chinese Med Univ. 2020;44(10):929–48.

Wu RM, Jiang B, Li H, Dang WZ, Bao WL, Li HD, et al. A network pharmacology approach to discover action mechanisms of Yangxinshi Tablet for improving energy metabolism in chronic ischemic heart failure. J Ethnopharmacol. 2019;246:112227.CrossRef

10.

Huang L, Xie D, Yu Y, Liu H, Shi Y, Shi T, et al. TCMID 2.0: a comprehensive resource for TCM. Nucleic Acids Res. 2018;46(D1):D1117–20. https://doi.org/10.1093/nar/gkx1028.CrossRefPubMed

11.

Wang X, Shen Y, Wang S, Li S, Zhang W, Liu X, et al. PharmMapper 2017 update: a web server for potential drug target identification with a comprehensive target pharmacophore database. Nucleic Acids Res. 2017;45(W1):W356–60. https://doi.org/10.1093/nar/gkx374.CrossRefPubMedPubMedCentral

12.

Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, et al. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatics. 2016;54:31–3.CrossRef

13.

Prasad TSK, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, et al. Human protein reference Database-2009 update. Nucleic Acids Res. 2009;37(Database):D767–72. https://doi.org/10.1093/nar/gkn892.CrossRef

14.

Fechtner S, Singh A, Chourasia M, Ahmed S. Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1 beta signaling in rheumatoid arthritis synovial fibroblasts. Toxicol Appl Pharmacol. 2017;329:112–20. https://doi.org/10.1016/j.taap.2017.05.016.CrossRefPubMedPubMedCentral

15.

Tykocinski LO, Lauffer AM, Bohnen A, Kaul NC, Krienke S, Tretter T, et al. Synovial fibroblasts selectively suppress Th1 cell responses through IDO1-mediated tryptophan catabolism. J Immunol. 2017;198(8):3109–17.CrossRef

16.

Liu R, Hao DL, Xu WY, Li JJ, Li XR, Shen D, et al. beta-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice. Pharm Biol. 2019;57(1):161–8. https://doi.org/10.1080/13880209.2019.1577461.CrossRefPubMedPubMedCentral

17.

Wu Y, Lin Z, Yan Z, Wang Z, Fu X, Yu K. Sinomenine contributes to the inhibition of the inflammatory response and the improvement of osteoarthritis in mouse-cartilage cells by acting on the Nrf2/HO-1 and NF-kappaB signaling pathways. Int Immunopharmacol. 2019;75:105715. https://doi.org/10.1016/j.intimp.2019.105715.CrossRefPubMed

18.

Yang J, Zhao S, Yang X, Zhang H, Zheng P, Wu H. Inhibition of B-cell apoptosis is mediated through increased expression of Bcl-2 in patients with rheumatoid arthritis. Int J Rheum Dis. 2016;19(2):134–40. https://doi.org/10.1111/1756-185X.12706.CrossRefPubMed

19.

López-Hoyos M, Marquina R, Tamayo E, González-Rojas J, Izui S, Merino R, et al. Defects in the regulation of B cell apoptosis are required for the production of citrullinated peptide autoantibodies in mice. Arthritis Rheum. 2003;48(8):2353–61. https://doi.org/10.1002/art.11107.CrossRefPubMed

20.

Bemis EA, Norris JM, Seifert J, Frazer-Abel A, Okamoto Y, Feser ML, et al. Complement and its environmental determinants in the progression of human rheumatoid arthritis. Mol Immunol. 2019;112:256–65.CrossRef

21.

Choi S, Lee K, Jung H, Park N, Kang J, Nam K-H, et al. Kruppel-Like Factor 4 Positively Regulates Autoimmune Arthritis in Mouse Models and Rheumatoid Arthritis in Patients via Modulating Cell Survival and Inflammation Factors of Fibroblast-Like Synoviocyte. Front Immunol. 2018;9:1339.CrossRef

22.

Leichsenring A, Bäcker I, Furtmüller PG, Obinger C, Lange F, Flemmig J. Long-term effects of (−)-Epigallocatechin Gallate (EGCG) on Pristane-induced arthritis (PIA) in female dark Agouti rats. PLoS One. 2016;11(3):e0152518. https://doi.org/10.1371/journal.pone.0152518.CrossRefPubMedPubMedCentral

23.

Storch H, Zimmermann B, Resch B, Tykocinski LO, Moradi B, Horn P, et al. Activated human B cells induce inflammatory fibroblasts with cartilage-destructive properties and become functionally suppressed in return. Ann Rheum Dis. 2016;75(5):924–32. https://doi.org/10.1136/annrheumdis-2014-206965.CrossRefPubMed

24.

Teitsma XM, Yang W, Jacobs JWG, Petho-Schramm A, Borm MEA, Harms AC, et al. Baseline metabolic profiles of early rheumatoid arthritis patients achieving sustained drug-free remission after initiating treat-to-target tocilizumab, methotrexate, or the combination: insights from systems biology. Arthritis Res Ther. 2018;20(1):230. https://doi.org/10.1186/s13075-018-1729-2.CrossRefPubMedPubMedCentral

25.

Corr M, Lerman I, Keubel JM, Ronacher L, Misra R, Lund F, et al. Decreased Krev Interaction-Trapped 1 Expression Leads to Increased Vascular Permeability and Modifies Inflammatory Responses In Vivo. Arterioscl Throm Vas. 2012;32(11):2702.CrossRef

26.

Crow AR, Kapur R, Koernig S, Campbell IK, Jen CC, Mott PJ, et al. Treating murine inflammatory diseases with an anti-erythrocyte antibody. Sci Transl Med. 2019;11:506.CrossRef

27.

Zhou J, Sun YY, Sun MY, Mao WA, Wang L, Zhang J, et al. Prim-O-glucosylcimifugin attenuates Lipopolysaccharideinduced inflammatory response in RAW 264.7 macrophages. Pharmacogn Mag. 2017;13(51):378–84. https://doi.org/10.4103/pm.pm_323_16.CrossRefPubMedPubMedCentral

28.

Naveed M, Hejazi V, Abbas M, Kamboh AA, Khan GJ, Shumzaid M, et al. Chlorogenic acid (CGA): a pharmacological review and call for further research. Biomed Pharmacother. 2018;97:67–74. https://doi.org/10.1016/j.biopha.2017.10.064.CrossRefPubMed

29.

Park B, Jo K, Lee TG, Hyun SW, Kim JS, Kim CS. Polydatin Inhibits NLRP3 Inflammasome in Dry Eye Disease by Attenuating Oxidative Stress and Inhibiting the NF-kappaB Pathway. Nutrients. 2019;11:11.

30.

Chen XJ, Shen YS, He MC, Yang F, Yang P, Pang FX, et al. Polydatin promotes the osteogenic differentiation of human bone mesenchymal stem cells by activating the BMP2-Wnt/beta-catenin signaling pathway. Biomed Pharmacother. 2019;112:108746. https://doi.org/10.1016/j.biopha.2019.108746.CrossRefPubMed

31.

Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004;50(2):380–6. https://doi.org/10.1002/art.20018.CrossRefPubMed

32.

Bohler C, Radner H, Smolen JS, Aletaha D. Serological changes in the course of traditional and biological disease modifying therapy of rheumatoid arthritis. Ann Rheum Dis. 2013;72(2):241–4. https://doi.org/10.1136/annrheumdis-2012-202297.CrossRefPubMed

33.

Shabgah AG, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohammadi M. The role of BAFF and APRIL in rheumatoid arthritis. J Cell Physiol. 2019;234(10):17050–63. https://doi.org/10.1002/jcp.28445.CrossRefPubMed

34.

Humby F, Bombardieri M, Manzo A, Kelly S, Blades MC, Kirkham B, et al. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid Synovium. PLoS Med. 2009;6(1):59–75.CrossRef

35.

Rivellese F, Mauro D, Nerviani A, Pagani S, Fossati-Jimack L, Messemaker T, et al. Mast cells in early rheumatoid arthritis associate with disease severity and support B cell autoantibody production. Ann Rheum Dis. 2018;77(12):1773–81. https://doi.org/10.1136/annrheumdis-2018-213418.CrossRefPubMed

36.

Fortea-Gordo P, Nuno L, Villalba A, Peiteado D, Monjo I, Sanchez-Mateos P, et al. Two populations of circulating PD-1hiCD4 T cells with distinct B cell helping capacity are elevated in early rheumatoid arthritis. Rheumatology (Oxford). 2019;58(9):1662–73. https://doi.org/10.1093/rheumatology/kez169.CrossRef

37.

Kaegi C, Wuest B, Schreiner J, Steiner UC, Vultaggio A, Matucci A, et al. Systematic review of safety and efficacy of rituximab in treating immune-mediated disorders. Front Immunol. 2019;10:1990. https://doi.org/10.3389/fimmu.2019.01990.CrossRefPubMedPubMedCentral

38.

Caudwell V, Porteu F, Calender A, Pangburn MK, Halbwachs-Mecarelli L. Complement alternative pathway activation and control on membranes of human lymphoid B cell lines. Eur J Immunol. 1990;20(12):2643–50. https://doi.org/10.1002/eji.1830201218.CrossRefPubMed

39.

Nikitin PA, Rose EL, Byun TS, Parry GC, Panicker S. C1s inhibition by BIVV009 (Sutimlimab) prevents complement-enhanced activation of autoimmune human B cells in vitro. J Immunol. 2019;202(4):1200–9. https://doi.org/10.4049/jimmunol.1800998.CrossRefPubMedPubMedCentral

40.

Buhe V, Pers JO, Marianowski R, Berthou C, Youinou P, Loisel S. Development of a murine model to dissect the CpG-oligonucleotide-enhancement of the killing of human B cells by rituximab. J Autoimmun. 2010;34(2):136–44. https://doi.org/10.1016/j.jaut.2009.08.007.CrossRefPubMed

41.

Romeo SG, Alawi KM, Rodrigues J, Singh A, Kusumbe AP, Ramasamy SK. Endothelial proteolytic activity and interaction with non-resorbing osteoclasts mediate bone elongation. Nat Cell Biol. 2019;21(4):430–41. https://doi.org/10.1038/s41556-019-0304-7.CrossRefPubMed

42.

Liu X, Zhu Y, Zheng W, Qian T, Wang H, Hou X. Antagonism of NK-1R using aprepitant suppresses inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes. Artificial Cells Nanomed Biotechnol. 2019;47(1):1628–34. https://doi.org/10.1080/21691401.2019.1573177.CrossRef

43.

Lee J, Son HS, Lee HI, Lee GR, Jo YJ, Hong SE, et al. Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling. FASEB J. 2019;33(2):2026–36. https://doi.org/10.1096/fj.201800866RR.CrossRefPubMed

44.

Tebib J, Mariette X, Bourgeois P, Flipo RM, Gaudin P, Le Loet X, et al. Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study. Arthritis Res Ther. 2009;11:3.CrossRef

45.

Roskoski R Jr. Properties of FDA-approved small molecule protein kinase inhibitors. Pharmacol Res. 2019;144:19–50. https://doi.org/10.1016/j.phrs.2019.03.006.CrossRefPubMed

46.

Huang CY, Lin HJ, Chen HS, Cheng SY, Hsu HC, Tang CH. Thrombin promotes matrix metalloproteinase-13 expression through the PKCdelta c-Src/EGFR/PI3K/Akt/AP-1 signaling pathway in human chondrocytes. Mediat Inflamm. 2013;2013:326041.CrossRef

Title: Network analysis indicating the pharmacological mechanism of Yunpi-Qufeng-Chushi-prescription in prophylactic treatment of rheumatoid arthritis
Authors: Lin Li
Donghai Zhou
Qiuping Liu
Dianming Li
Qiao Wang
Xiaowei Shi
Chengping Wen
Lin Huang
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Rheumatoid Arthritis
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-021-03311-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Network analysis indicating the pharmacological mechanism of Yunpi-Qufeng-Chushi-prescription in prophylactic treatment of rheumatoid arthritis

Abstract

Background

Methods

Result

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Result

Conclusion

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