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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

2019 Impact Factor: 3.421

Frontiers of Medicine  2019, Vol. 13 Issue (5): 564-574   https://doi.org/10.1007/s11684-018-0676-2
  本期目录
Deciphering the pharmacological mechanism of Guan-Jie-Kang in treating rat adjuvant-induced arthritis using omics analysis
Hudan Pan1, Yanfang Zheng1,2, Zhongqiu Liu3, Zhongwen Yuan1, Rutong Ren1, Hua Zhou1, Ying Xie1(), Liang Liu1()
1. State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China
2. Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
3. International Institute for Translational Research of Traditional Chinese Medicine of Guangzhou University of Chinese Medicine, Guangzhou 510006, China
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Abstract

Traditional Chinese medicine (TCM) formulas have attracted increasing attention worldwide in the past few years for treating complex disease including rheumatoid arthritis. However, their mechanisms are complex and remain unclear. Guan-Jie-Kang (GJK), a prescription modified from “Wu Tou Decoction,” was found to significantly relieve arthritis symptoms in rats with adjuvant-induced arthritis after 30-day treatment, especially in the 24 g/kg/day group. By analyzing 1749 targets related to 358 compounds in the five herbs of GJK, we identified the possible anti-arthritis pathways of GJK, including the calcium signaling and metabolic pathways. Bone damage levels were assessed by micro-computed tomography, and greater bone protective effect was observed with GJK treatment than with methotrexate. Receptor activator of nuclear factor κB ligand (RANKL)–RANK signaling, which is related to calcium signaling, was significantly regulated by GJK. Moreover, a target metabolomics assay of serum was conducted; 17 metabolic biomarkers showed significant correlations with treatment. An integrated pathway analysis revealed that pyruvate metabolism, purine metabolism, and glycolysis metabolism were significantly associated with the effects of GJK in arthritis treatment. Thus, this study establishes a new omics analytical method integrated with bioinformatics analysis for elucidating the multi-pathway mechanisms of TCM.

Key wordsrheumatoid arthritis    traditional Chinese medicine    pharmacological mechanism    metabolism    adjuvant-induced arthritis    omics analysis
收稿日期: 2018-07-19      出版日期: 2019-10-14
Corresponding Author(s): Ying Xie,Liang Liu   
 引用本文:   
. [J]. Frontiers of Medicine, 2019, 13(5): 564-574.
Hudan Pan, Yanfang Zheng, Zhongqiu Liu, Zhongwen Yuan, Rutong Ren, Hua Zhou, Ying Xie, Liang Liu. Deciphering the pharmacological mechanism of Guan-Jie-Kang in treating rat adjuvant-induced arthritis using omics analysis. Front. Med., 2019, 13(5): 564-574.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-018-0676-2
https://academic.hep.com.cn/fmd/CN/Y2019/V13/I5/564
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1 TR Mikuls. Co-morbidity in rheumatoid arthritis. Best Pract Res Clin Rheumatol 2003; 17(5): 729–752
https://doi.org/10.1016/S1521-6942(03)00041-X pmid: 12915155
2 DL Scott, F Wolfe, TW Huizinga. Rheumatoid arthritis. Lancet 2010; 376(9746): 1094–1108
https://doi.org/10.1016/S0140-6736(10)60826-4 pmid: 20870100
3 SE Gabriel. The epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am 2011; 27(2): 269–281
4 GS Firestein. Evolving concepts of rheumatoid arthritis. Nature 2003; 423(6937): 356–361
https://doi.org/10.1038/nature01661 pmid: 12748655
5 NJ Cooper. Economic burden of rheumatoid arthritis: a systematic review. Rheumatology (Oxford) 2000; 39(1): 28–33
https://doi.org/10.1093/rheumatology/39.1.28 pmid: 10662870
6 JA Singh, KG Saag, SL Bridges Jr, EA Akl, RR Bannuru, MC Sullivan, E Vaysbrot, C McNaughton, M Osani, RH Shmerling, JR Curtis, DE Furst, D Parks, A Kavanaugh, J O’Dell, C King, A Leong, EL Matteson, JT Schousboe, B Drevlow, S Ginsberg, J Grober, EW St Clair, E Tindall, AS Miller, T McAlindon. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol 2016; 68(1): 1–26
https://doi.org/10.1002/art.39480 pmid: 26545940
7 JA Singh, R Christensen, GA Wells, ME Suarez-Almazor, R Buchbinder, MA Lopez-Olivo, ET Ghogomu, P Tugwell. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Sao Paulo Med J 2010; 128(5): 309–310
https://doi.org/10.1590/S1516-31802010000500013 pmid: 21181074
8 GS Firestein, IB McInnes. Immunopathogenesis of rheumatoid arthritis. Immunity 2017; 46(2): 183–196
https://doi.org/10.1016/j.immuni.2017.02.006 pmid: 28228278
9 AE Koch. The pathogenesis of rheumatoid arthritis. Am J Orthop (Belle Mead NJ) 2007; 36(7 Suppl): 5–8
pmid: 17694191
10 I Haro, R Sanmartí. Rheumatoid arthritis: current advances in pathogenesis, diagnosis and therapy. Curr Top Med Chem 2013; 13(6): 697
https://doi.org/10.2174/15680266113139990091 pmid: 23574517
11 XR Wang, Y Su, Y An, YS Zhou, XY Zhang, TJ Duan, JX Zhu, XF Li, CH Wang, LZ Wang, YF Wang, R Yang, GC Wang, X Lu, P Zhu, LN Chen, Y Wang, XY Wang, HT Jin, JT Liu, HY Chen, P Wei, JX Wang, XY Liu, L Sun, LF Cui, R Shu, BL Liu, ZL Zhang, GT Li, ZB Li, J Yang, JF Li, B Jia, FX Zhnag, , JM Tao, JY Lin, MQ Wei, XM Liu, D Ke, SX Hu, C Ye, SL Han, XY Yang, H Li, CB Huang, M Gao, P Lai, LJ Song, R Mu, ZG Li. Survey of tumor necrosis factor inhibitors application in patients with rheumatoid arthritis in China. J Peking Univ (Health Sci) (Beijing Da Xue Xue Bao Yi Xue Ban) 2012. 44(2): p. 182–7 (in Chinese)
12 C Xu, X Wang, R Mu, L Yang, Y Zhang, S Han, X Li, Y Wang, G Wang, P Zhu, H Jin, L Sun, H Chen, L Cui, Z Zhang, Z Li, J Li, F Zhang, J Lin, X Liu, S Hu, X Yang, B Lai, X Li, X Wang, Y Su, Z Li. Societal costs of rheumatoid arthritis in China: a hospital-based cross-sectional study. Arthritis Care Res (Hoboken) 2014; 66(4): 523–531
https://doi.org/10.1002/acr.22160 pmid: 24023001
13 J Liu, Y Sun. How does Chinese medicine target cytokine imbalance in rheumatoid arthritis? Chin J Integr Med 2013; 19(11): 874–880
https://doi.org/10.1007/s11655-013-1620-6 pmid: 24170633
14 J Liu, Z Chen. Traditional Chinese medicine in the new century. Front Med 2011; 5(2): 111–114
https://doi.org/10.1007/s11684-011-0125-y pmid: 21695612
15 Z Xiang, X Wang, T Liu, D Lv. Thoughts and exploration on studying pharmacological mechanism of traditional Chinese medicine using network biology approach. China J Chin Materia Medica (Zhongguo Zhong Yao Za Zhi) 2012; 37(2): 146–151 (in Chinese)
pmid: 22737841
16 J Wu, Y Xie, Z Xiang, C Wang, H Zhou, L Liu. Simultaneous determination of multiple components in Guanjiekang in rat plasma via the UPLC-MS/MS method and its application in pharmacokinetic study. Molecules 2016; 21(12): E1732
https://doi.org/10.3390/molecules21121732 pmid: 27999285
17 Y Ma, K Zhou, J Fan, S Sun. Traditional Chinese medicine: potential approaches from modern dynamical complexity theories. Front Med 2016; 10(1): 28–32
https://doi.org/10.1007/s11684-016-0434-2 pmid: 26809465
18 R Xue, Z Fang, M Zhang, Z Yi, C Wen, T Shi. TCMID: traditional Chinese medicine integrative database for herb molecular mechanism analysis. Nucleic Acids Res 2013; 41(Database issue): D1089–D1095
pmid: 23203875
19 S Li, B Zhang. Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med 2013; 11(2): 110–120
https://doi.org/10.1016/S1875-5364(13)60037-0 pmid: 23787177
20 C Wang, Y Xie, Z Xiang, H Zhou, L Liu. Simultaneous determination of thirteen major active compounds in Guanjiekang preparation by UHPLC-QQQ-MS/MS. J Pharm Biomed Anal 2016; 118: 315–321
https://doi.org/10.1016/j.jpba.2015.10.043 pmid: 26588049
21 X1 Cai, YF Wong, H Zhou, ZQ Liu, Y Xie, ZH Jiang, ZX Bian, HX Xu, L Liu. Manipulation of the induction of adjuvant arthritis in Sprague-Dawley rats. Inflamm Res 2006; 55(9): 368–377
https://doi.org/10.1007/s00011-006-6026-x pmid: 17122958
22 J Zuo, Y Xia, X Li, JW Chen. Therapeutic effects of dichloromethane fraction of Securidaca inappendiculata on adjuvant-induced arthritis in rat. J Ethnopharmacol 2014; 153(2): 352–358
https://doi.org/10.1016/j.jep.2014.02.015 pmid: 24583103
23 AB Lemmey. Rheumatoid cachexia: the undiagnosed, untreated key to restoring physical function in rheumatoid arthritis patients? Rheumatology (Oxford) 2016; 55(7): 1149–1150
https://doi.org/10.1093/rheumatology/kev412 pmid: 26672906
24 SV Komarova, MF Pilkington, AF Weidema, SJ Dixon, SM Sims. RANK ligand-induced elevation of cytosolic Ca2+ accelerates nuclear translocation of nuclear factor κ B in osteoclasts. J Biol Chem 2003; 278(10): 8286–8293
https://doi.org/10.1074/jbc.M206421200 pmid: 12496256
25 P Zhang, J Li, Y Han, XW Yu, L Qin. Traditional Chinese medicine in the treatment of rheumatoid arthritis: a general review. Rheumatol Int 2010; 30(6): 713–718
https://doi.org/10.1007/s00296-010-1370-0 pmid: 20204371
26 P Hemon, Y Renaudineau, M Debant, N Le Goux, S Mukherjee, W Brooks, O Mignen. Calcium signaling: from normal B cell development to tolerance breakdown and autoimmunity. Clin Rev Allergy Immunol 2017; 53(2): 141–165
https://doi.org/10.1007/s12016-017-8607-6 pmid: 28500564
27 H Kajiya. Calcium signaling in osteoclast differentiation and bone resorption. Adv Exp Med Biol 2012; 740: 917–932
https://doi.org/10.1007/978-94-007-2888-2_41 pmid: 22453976
28 T Negishi-Koga, H Takayanagi. Ca2+-NFATc1 signaling is an essential axis of osteoclast differentiation. Immunol Rev 2009; 231(1): 241–256
https://doi.org/10.1111/j.1600-065X.2009.00821.x pmid: 19754901
29 E Leah. Rheumatoid arthritis. Assessment of CVD in patients with RA by strain imaging. Nat Rev Rheumatol 2013; 9(9): 506
https://doi.org/10.1038/nrrheum.2013.117 pmid: 23917955
30 BJ Paul, HI Kandy, V Krishnan. Pre-rheumatoid arthritis and its prevention. Eur J Rheumatol 2017; 4(2): 161–165
https://doi.org/10.5152/eurjrheum.2017.16006 pmid: 28638695
31 VR da Cunha, CV Brenol, JC Brenol, RM Xavier. Rheumatoid arthritis and metabolic syndrome. Rev Bras Reumatol 2011; 51(3): 260–268
pmid: 21625814
32 X Chang, C Wei. Glycolysis and rheumatoid arthritis. Int J Rheum Dis 2011; 14(3): 217–222
https://doi.org/10.1111/j.1756-185X.2011.01598.x pmid: 21816017
33 Z Yang, Y Shen, H Oishi, EL Matteson, L Tian, JJ Goronzy, CM Weyand. Restoring oxidant signaling suppresses proarthritogenic T cell effector functions in rheumatoid arthritis. Sci Transl Med 2016; 8(331): 331ra38
https://doi.org/10.1126/scitranslmed.aad7151 pmid: 27009267
34 LR Gray, SC Tompkins, EB Taylor. Regulation of pyruvate metabolism and human disease. Cell Mol Life Sci 2014; 71(14): 2577–2604
https://doi.org/10.1007/s00018-013-1539-2 pmid: 24363178
35 A Perl. Review: Metabolic control of immune system activation in rheumatic diseases. Arthritis Rheumatol 2017; 69(12): 2259–2270
https://doi.org/10.1002 /art.40223 pmid: 28841779
36 CM Weyand, JJ Goronzy. Immunometabolism in early and late stages of rheumatoid arthritis. Nat Rev Rheumatol 2017; 13(5): 291–301
https://doi.org/10.1038/nrrheum.2017.49 pmid: 28360422
37 BN Cronstein. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol Rev 2005; 57(2): 163–172
https://doi.org/10.1124/pr.57.2.3 pmid: 15914465
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