Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

CP-25, a compound derived from paeoniflorin: research advance on its pharmacological actions and mechanisms in the treatment of inflammation and immune diseases

Abstract

Total glycoside of paeony (TGP) has been widely used to treat inflammation and immune diseases in China. Paeoniflorin (Pae) is the major active component of TGP. Although TGP has few adverse drug reactions, the slow onset and low bioavailability of Pae limit its clinical use. Enhanced efficacy without increased toxicity is pursued in developing new agents for inflammation and immune diseases. As a result, paeoniflorin-6′-O-benzene sulfonate (CP-25) derived from Pae, is developed in our group, and exhibits superior bioavailability and efficacy than Pae. Here we describe the development process and research advance on CP-25. The pharmacokinetic parameters of CP-25 and Pae were compared in vivo and in vitro. CP-25 was also compared with the first-line drugs methotrexate, leflunomide, and hydroxychloroquine in their efficacy and adverse effects in arthritis animal models and experimental Sjögren’s syndrome. We summarize the regulatory effects of CP-25 on inflammation and immune-related cells, elucidate the possible mechanisms, and analyze the therapeutic prospects of CP-25 in inflammation and immune diseases, as well as the diseases related to its potential target G-protein-coupled receptor kinases 2 (GRK2). This review suggests that CP-25 is a promising agent in the treatment of inflammation and immune diseases, which requires extensive investigation in the future. Meanwhile, this review provides new ideas about the development of anti-inflammatory immune drugs.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: The development process of CP-25.
Fig. 2: Effects of CP-25 on cells and possible mechanisms.

References

  1. 1.

    Jin Z. To explore the medicine of Cassia twig and Paeonia lactiflora in “Synopsis of Golden Chamber”. forum on traditional Chinese. Medicine. 2008;23:5–6.

    Google Scholar 

  2. 2.

    Ma SH, Wang HF, Liu JL, Huo XP, Zhao XR, Cao QW, et al. Inhibition of Paeoniflorin on TNF-α-induced TNF-α receptor type I /nuclear factor-κB signal transduction in endothelial cells. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2016;36:339–44.

    Google Scholar 

  3. 3.

    Kaneda M, Litaka Y, Shibata S. The absolute structures of paeoniflorin, albiflorin, oxypaeoniflorin and benzoylpaeoniflorin isolated from chinese paeony root. Tetrahedron. 1972;28:4309–17.

    CAS  Google Scholar 

  4. 4.

    Wang C, Yuan J, Yang ZY, Nie XX, Song LH, Wei W. Pharmacokinetics of paeoniflorin microemulsion after repeated dosing in rats with adjuvant arthritis. Pharmazie. 2012;67:997–1001.

    CAS  Google Scholar 

  5. 5.

    Takeda S, Isono T, Wakui Y, Matsuzaki Y, Sasaki H, Amagaya S, et al. Absorption and excretion of paeoniflorin in rats. J Pharm Pharmacol. 1995;47:1036–40.

    CAS  Google Scholar 

  6. 6.

    He JX, Akao T, Tani T. Influence of co-administered antibiotics on the pharmacokinetic fate in rats of paeoniflorin and its active metabolite paeonimetabolin-I from Shaoyao-Gancao-tang. J Pharm Pharmacol. 2003;55:313–21.

    CAS  Google Scholar 

  7. 7.

    Hsiu SL, Lin YT, Wen KC, Hou YC, Chao PD. A deglucosylated metabolite of paeoniflorin of the root of Paeonia lactiflora and its pharmacokinetics in rats. Planta Med. 2003;69:1113–8.

    CAS  Google Scholar 

  8. 8.

    Liu ZQ, Jiang ZH, Liu L, Hu M. Mechanisms responsible for poor oral bioavailability of paeoniflorin: Role of intestinal disposition and interactions with sinomenine. Pharm Res. 2006;23:2768–80.

    CAS  Google Scholar 

  9. 9.

    Chan K, Liu ZQ, Jiang ZH, Zhou H, Wong YF, Xu HX, et al. The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model. J Ethnopharmacol. 2006;103:425–32.

    CAS  Google Scholar 

  10. 10.

    Wu H, Zhu Z, Zhang G, Zhao L, Zhang H, Zhu D, et al. Comparative pharmacokinetic study of paeoniflorin after oral administration of pure paeoniflorin, extract of Cortex Moutan and Shuang-Dan prescription to rats. J Ethnopharmacol. 2009;125:444–9.

    CAS  Google Scholar 

  11. 11.

    Yang X, Guo J, Xu W. Absorption and transport characteristic of paeoniflorin and its derivatives in model of Caco-2 cell monolayers. Chinese Traditional and Herbal. Chin Tradit Herb Drugs. 2013;44:2097–104.

    CAS  Google Scholar 

  12. 12.

    Cheng Y, Peng C, Wen F, Zhang H. Pharmacokinetic comparisons of typical constituents in white peony root and sulfur fumigated white peony root after oral administration to mice. J Ethnopharmacol. 2010;129:167–73.

    CAS  Google Scholar 

  13. 13.

    Wang C, Yuan J, Wei W. Study on paeoniflorin-6’O-benzene sulfonate’s physicochemical property. Acta Univ Med Anhui. 2014;49:202–5.

  14. 14.

    Zhao M, Zhou P, Yu J, James A, Xiao F, Wang C, et al. The tissue distribution and excretion study of paeoniflorin-6’-O-benzene sulfonate (CP-25) in rats. Inflammopharmacology. 2019;27:969–74.

    CAS  Google Scholar 

  15. 15.

    Yang XD, Wang C, Zhou P, Yu J, Asenso J, Ma Y, et al. Absorption characteristic of paeoniflorin-6’-O-benzene sulfonate (CP-25) in in situ single-pass intestinal perfusion in rats. Xenobiotica. 2016;46:775–83.

    CAS  Google Scholar 

  16. 16.

    Wang J, Wang C, Xiao F, Ma Y, Wei W. Study on absorption mechanism of paeoniflorin-6’-O-benzene sulfonate (CP-25) in Caco-2 cells. Acta Univ Med Anhui. 2018;53:1751–6.

    Google Scholar 

  17. 17.

    Wang C, Yuan J, Zhang LL, Wei W. Pharmacokinetic comparisons of Paeoniflorin and Paeoniflorin-6’O-benzene sulfonate in rats via different routes of administration. Xenobiotica. 2016;46:1142–50.

    CAS  Google Scholar 

  18. 18.

    Szakács G, Váradi A, Ozvegy-Laczka C, Sarkadi B. The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Drug Discov Today. 2008;13:379–93.

    Google Scholar 

  19. 19.

    Wang C, Wei W. Research progress of pharmacokinetic study on paeoniflorin. Chin Pharmacol Bull. 2014;30:1646–50.

    CAS  Google Scholar 

  20. 20.

    Tang H, Wu YJ, Xiao F, Wang B, Asenso J, Wang Y, et al. Regulation of CP-25 on P-glycoprotein in synoviocytes of rats with adjuvant arthritis. Biomed Pharmacother. 2019;119:109432.

    CAS  Google Scholar 

  21. 21.

    Asenso J, Yu J, Xiao F, Zhao M, Wang J, Wu Y, et al. Methotrexate improves the anti-arthritic effects of Paeoniflorin-6’-O-benzene sulfonate by enhancing its pharmacokinetic properties in adjuvant-induced arthritis rats. Biomed Pharmacother. 2019;112:108644.

    CAS  Google Scholar 

  22. 22.

    Wu YJ, Zhao MY, Wang J, Tang H, Wang B, Xiao F, et al. Absorption and efflux characteristics of CP-25 in plasma and peripheral blood mononuclear cells of rats by UPLC-MS/MS. Biomed Pharmacother 2018;108:1651–7.

    CAS  Google Scholar 

  23. 23.

    Daohua Shi, Jie Deng, Qiuyan Lian. Relationship between the protein concentration and total concentration of valproate acid in plasma on free concentration. Chin J Clin Pharmacol. 2014;7:1006–8.

    Google Scholar 

  24. 24.

    Yu J, Xiao F, Asenso J, Peng Z, Yang XD, Wang C, et al. Simultaneous determination of paeoniflorin-6′-O-benzene sulfonate (CP-25) and its active paeoniflorin (Pae) metabolite in rat plasma using UPLC-MS/MS: an application for pharmacokinetic studies. RSC Adv. 2016;113209–18.

  25. 25.

    Chang Y, Jia X, Wei F, Wang C, Sun X, Xu S, et al. CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage. Sci Rep. 2016;6:26239.

    CAS  Google Scholar 

  26. 26.

    Chen J, Wang Y, Wu H, Yan S, Chang Y, Wei W. A modified compound from paeoniflorin, CP-25, suppressed immune responses and synovium inflammation in collagen-induced arthritis mice. Front Pharmacol. 2018;9:563.

    Google Scholar 

  27. 27.

    Burmester GR, Pope JE. Novel treatment strategies in rheumatoid arthritis. Lancet. 2017;389:2338–48.

    Google Scholar 

  28. 28.

    Tanaka Y. Rheumatoid arthritis: DMARD de-escalation - let the patient guide you. Nat Rev Rheumatol. 2017;13:637–8.

    Google Scholar 

  29. 29.

    McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet. 2017;389:2328–37.

    CAS  Google Scholar 

  30. 30.

    Kavanaugh A, van Vollenhoven RF, Fleischmann R, Emery P, Sainsbury I, Florentinus S, et al. Testing treat-to-target outcomes with initial methotrexate monotherapy compared with initial tumour necrosis factor inhibitor (adalimumab) plus methotrexate in early rheumatoid arthritis. Ann Rheum Dis. 2018;77:289–92.

    CAS  Google Scholar 

  31. 31.

    Nogueira E, Lager F, Le Roux D, Nogueira P, Freitas J, Charvet C, et al. Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice. J Biomed Nanotechnol. 2015;11:2243–52.

    CAS  Google Scholar 

  32. 32.

    Aletaha D, Stamm T, Kapral T, Eberl G, Grisar J, Machold KP, et al. Survival and effectiveness of leflunomide compared with methotrexate and sulfasalazine in rheumatoid arthritis: a matched observational study. Ann Rheum Dis. 2003;62:944–51.

    CAS  Google Scholar 

  33. 33.

    Xiang N, Li XM, Zhang MJ, Zhao DB, Zhu P, Zuo XX, et al. Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis. Int Immunopharmacol. 2015;28:802–7.

    CAS  Google Scholar 

  34. 34.

    Chen Z, Li XP, Li ZJ, Xu L, Li XM. Reduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis. Int Immunopharmacol. 2013;15:474–7.

    CAS  Google Scholar 

  35. 35.

    Yang X, Zhao Y, Jia X, Wang C, Wu Y, Zhang L, et al. CP-25 combined with MTX/ LEF ameliorates the progression of adjuvant-induced arthritis by the inhibition on GRK2 translocation. Biomed Pharmacother. 2019;110:834–43.

    CAS  Google Scholar 

  36. 36.

    Chen X, Zhang P, Liu Q, Zhang Q, Gu F, Xu S, et al. Alleviating effect of paeoniflorin-6’-O-benzene sulfonate in antigen-inducedexperimental Sjögren’s syndrome by modulating B lymphocyte migrationvia CXCR5-GRK2-ERK/p38 signaling pathway. Int Immunopharmacol. 2020;80:106199. https://doi.org/10.1016/j.intimp.2020.106199.

    CAS  Google Scholar 

  37. 37.

    Vivino FB, Carsons SE, Foulks G, Daniels TE, Parke A, Brennan MT, et al. New treatment guidelines for Sjögren’s disease. Rheum Dis Clin N Am. 2016;42:531–51.

    Google Scholar 

  38. 38.

    Li H, Sun X, Zhang J, Sun Y, Huo R, Li H, et al. Paeoniflorin ameliorates symptoms of experimental Sjogren’s syndrome associated with down-regulating Cyr61 expression. Int Immunopharmacol. 2016;30:27–35.

    CAS  Google Scholar 

  39. 39.

    Zhang L, Wei W. Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony. Pharmacol Ther. 2020;207:107452.

    CAS  Google Scholar 

  40. 40.

    Gu F, Xu S, Zhang P, Chen X, Wu Y, Wang C, et al. CP-25 alleviates experimental Sjögren’s syndrome features in NOD/Ltj mice and modulates T lymphocyte subsets. Basic Clin Pharmacol Toxicol. 2018;123:423–34. https://doi.org/10.1111/bcpt.13025.

  41. 41.

    Wu Y, Chen W, Chen H, Zhang L, Chang Y, Yan S, et al. The elevated secreted immunoglobulin D enhanced the activation of peripheral blood mononuclear cells in rheumatoid arthritis. PLoS ONE. 2016;11:e0147788.

    Google Scholar 

  42. 42.

    Wu YJ, Chen WS, Chen HS, Dai X, Dong J, Wang Y, et al. The immunoglobulin D Fc receptor expressed on fibroblast-like synoviocytes from patients with rheumatoid arthritis contributes to the cell activation. Acta Pharmacol Sin. 2017;38:1466–74.

    CAS  Google Scholar 

  43. 43.

    Wu YJ, Chen HS, Chen WS, Dong J, Dong XJ, Dai X, et al. CP-25 attenuates the activation of CD4+ T cells stimulated with immunoglobulin D in human. Front Pharmacol. 2018;9:4. https://doi.org/10.3389/fphar.2018.00004.

    Google Scholar 

  44. 44.

    Zhang F, Shu JL, Li Y, Wu YJ, Zhang XZ, Han L, et al. CP-25, a novel anti-inflammatory and immunomodulatory drug, inhibits the functions of activated human B cells through regulating BAFF and TNF-alpha signaling and comparative efficacy with biological agents. Front Pharmacol. 2017;8:933.

    Google Scholar 

  45. 45.

    Shu JL, Zhang XZ, Han L, Zhang F, Wu YJ, Tang XY, et al. Paeoniflorin-6’-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents. Acta Pharmacol Sin. 2019;40:801–13.

    CAS  Google Scholar 

  46. 46.

    Li Y, Sheng K, Chen J, Wu Y, Zhang F, Chang Y, et al. Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25. Eur J Pharmacol. 2015;769:8–21.

    CAS  Google Scholar 

  47. 47.

    Jia XY, Chang Y, Sun XJ, Wei F, Wu YJ, Dai X, et al. Regulatory effects of paeoniflorin-6’-O-benzene sulfonate (CP-25) on dendritic cells maturation and activation via PGE2-EP4 signaling in adjuvant-induced arthritic rats. Inflammopharmacology. 2019;27:997–1010.

    CAS  Google Scholar 

  48. 48.

    Haringman JJ, Gerlag DM, Zwinderman AH, Smeets TJ, Kraan MC, Baeten D, et al. Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2005;64:834–8.

    CAS  Google Scholar 

  49. 49.

    Wang DD, Jiang MY, Wang W, Zhou WJ, Zhang YW, Yang M, et al. Paeoniflorin-6’-O-benzene sulfonate down-regulates CXCR4-Gβγ-PI3K/AKT mediated migration in fibroblast-like synoviocytes of rheumatoid arthritis by inhibiting GRK2 translocation. Biochem Biophys Res Commun. 2020;526:805–12.

    CAS  Google Scholar 

  50. 50.

    Jia XY, Chang Y, Wei F, Dai X, Wu YJ, Sun XJ, et al. CP-25 reverses prostaglandin E4 receptor desensitization-induced fibroblast-like synoviocyte dysfunction via the G protein-coupled receptor kinase 2 in autoimmune arthritis. Acta Pharmacol Sin. 2019;40:1029–39.

    CAS  Google Scholar 

  51. 51.

    Jia X, Wei F, Sun X, Chang Y, Xu S, Yang X, et al. CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFF-activated CD4+ T cells. J Ethnopharmacol. 2016;189:194–201.

    CAS  Google Scholar 

  52. 52.

    Yang X, Chang Y, Wei W. Endothelial dysfunction and inflammation: immunity in rheumatoid arthritis. Mediators Inflamm. 2016;2016:6813016.

    Google Scholar 

  53. 53.

    Han CC, Liu Q, Zhang Y, Li YF, Cui DQ, Luo TT, et al. CP-25 inhibits PGE2-induced angiogenesis by down-regulating EP4/AC/cAMP/PKA-mediated GRK2 translocation. Clin Sci. 2020;134:331–47.

    CAS  Google Scholar 

  54. 54.

    Zhang M, Gao M, Chen J, Song L, Wei W. CP-25 exerts anti-angiogenic effects on a rat model of adjuvant-induced arthritis by promoting GRK2-induced downregulation of CXCR4-ERK1/2 signaling in endothelial cells. Mol Med Rep. 2019;20:4831–42.

    CAS  Google Scholar 

  55. 55.

    Wu H, Chen X, Gu F, Zhang P, Xu S, Liu Q, et al. CP-25 alleviates antigen-induced experimental Sjögren’s syndrome in mice by inhibiting JAK1-STAT1/2-CXCL13 signaling and interfering with B-cell migration. Lab Investig. 2020. https://doi.org/10.1038/s41374-020-0453-0.

    Article  Google Scholar 

  56. 56.

    Yang X, Li S, Zhao Y, Li S, Zhao T, Tai Y, et al. GRK2 mediated abnormal transduction of PGE2-EP4-cAMP-CREB signaling induces the imbalance of macrophages polarization in collagen-induced arthritis mice. Cells. 2019;8:E1596.

    Google Scholar 

  57. 57.

    Steury MD, McCabe LR, Parameswaran N. G protein-coupled receptor kinases in the inflammatory response and signaling. Adv Immunol. 2017;136:227–77.

    CAS  Google Scholar 

  58. 58.

    Hagen SA, Kondyra AL, Grocott HP, El-Moalem H, Bainbridge D, Mathew JP, et al. Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells. Anesthesiology. 2003;98:343–8.

  59. 59.

    Vroon A, Heijnen CJ, Lombardi MS, Cobelens PM, Mayor F Jr, Caron MG, et al. Reduced GRK2 level in T cells potentiates chemotaxis and signaling in response to CCL4. J Leukoc Biol. 2004;75:901–9.

    CAS  Google Scholar 

  60. 60.

    Penela P, Ribas C, Sánchez-Madrid F, Mayor F Jr. G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub. Cell Mol Life Sci. 2019;76:4423–46.

    CAS  Google Scholar 

  61. 61.

    Grassi F, Cristino S, Toneguzzi S, Piacentini A, Facchini A, Lisignoli G. XCL12 chemokine up-regulates bone resorption and MMP-9 release by human osteoclasts: CXCL12 levels are increased in synovial and bone tissue of rheumatoid arthritis patients. J Cell Physiol. 2004;199:244–51.

    CAS  Google Scholar 

  62. 62.

    Kanbe K, Chiba J, Inoue Y, Taguchi M, Yabuki A. SDF-1 and CXCR4 in synovium are associated with disease activity and bone and joint destruction in patients with rheumatoid arthritis treated with golimumab. Mod Rheumatol. 2016;26:46–50.

    CAS  Google Scholar 

  63. 63.

    Whiteman M, Spencer JP, Zhu YZ, Armstrong JS, Schantz JT. Peroxynitrite-modified collagen-II induces p38/ERK and NF-kappaB-dependent synthesis of prostaglandin E2 and nitric oxide in chondrogenically differentiated mesenchymal progenitor cells. Osteoarthr Cartil. 2006;14:460–70.

    CAS  Google Scholar 

  64. 64.

    Elorza A, Penela P, Sarnago S, Mayor F Jr. MAPK-dependent degradation of G protein-coupled receptor kinase 2. J Biol Chem. 2003;278:29164–73.

    CAS  Google Scholar 

  65. 65.

    Fu X, Koller S, Abd Alla J, Quitterer U. Inhibition of G-protein-coupled receptor kinase 2 (GRK2) triggers the growth-promoting mitogen-activated protein kinase (MAPK) pathway. J Biol Chem. 2013;288:7738–55.

    CAS  Google Scholar 

  66. 66.

    Han FL, Liang F, Jiang TC, Liu M. Increased expression of CXCR5 and CXCL13 in mice with experimental autoimmune myocarditis. Eur Rev Med Pharmacol Sci. 2017;21:1860–7.

    Google Scholar 

  67. 67.

    Förster R, Mattis AE, Kremmer E, Wolf E, Brem G, Lipp M. A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell 1996;87:1037–47.

    Google Scholar 

  68. 68.

    Müller G, Lipp M. Signal transduction by the chemokine receptor CXCR5: structural requirements for G protein activation analyzed by chimeric CXCR1/CXCR5 molecules. Biol Chem. 2001;382:1387–97.

    Google Scholar 

  69. 69.

    Grech AP, Amesbury M, Chan T, Gardam S, Basten A, Brink R. TRAF2 differentially regulates the canonical and noncanonical pathways of NF-kappaB activation in mature B cells. Immunity. 2004;21:629–42.

    CAS  Google Scholar 

  70. 70.

    Chang Y, Zhang L, Wang C, Jia XY, Wei W. Paeoniflorin inhibits function of synoviocytes pretreated by rIL-1α and regulates EP4 receptor expression. J Ethnopharmacol. 2011;137:1275–82.

    CAS  Google Scholar 

  71. 71.

    Wang C, Yuan J, Wu HX, Chang Y, Wang QT, Wu YJ, et al. Paeoniflorin inhibits inflammatory responses in mice with allergic contact dermatitis by regulating the balance between inflammatory and anti-inflammatory cytokines. Inflamm Res. 2013;62:1035–44.

    CAS  Google Scholar 

  72. 72.

    Wu JJ, Sun WY, Hu SS, Zhang S, Wei W. A standardized extract from Paeonia lactiflora and Astragalus membranaceus induces apoptosis and inhibits the proliferation, migration and invasion of human hepatoma cell lines. Int J Oncol. 2013;43:1643–51.

    Google Scholar 

  73. 73.

    Yang HO, Ko WK, Kim JY, Ro HS. Paeoniflorin: an antihyperlipidemic agent from Paeonia lactiflora. Fitoterapia. 2004;75:45–9.

    CAS  Google Scholar 

  74. 74.

    Liu DZ, Xie KQ, Ji XQ, Ye Y, Jiang CL, Zhu XZ. Neuroprotective effect of paeoniflorin on cerebral ischemic rat by activating adenosine A1 receptor in a manner different from its classical agonists. Br J Pharmacol. 2005;146:604–11.

    CAS  Google Scholar 

  75. 75.

    Mushegian A, Gurevich VV, Gurevich EV. The origin and evolution of G protein-coupled receptor kinases. PLoS ONE. 2012;7:e33806.

    CAS  Google Scholar 

  76. 76.

    Penela P, Nogués L, Mayor F Jr. Role of G protein-coupled receptor kinases in cell migration. Curr Opin Cell Biol. 2014;27:10–7.

    CAS  Google Scholar 

  77. 77.

    Gurevich EV, Gainetdinov RR, Gurevich VV. G protein-coupled receptor kinases as regulators of dopamine receptor functions. Pharmacol Res. 2016;111:1–16.

    CAS  Google Scholar 

  78. 78.

    Hullmann J, Traynham CJ, Coleman RC, Koch WJ. The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development. Pharmacol Res. 2016;110:52–64.

    CAS  Google Scholar 

  79. 79.

    Ciccarelli M, Chuprun JK, Rengo G, Gao E, Wei Z, Peroutka RJ, et al. G protein-coupled receptor kinase 2 activity impairs cardiac glucose uptake and promotes insulin resistance after myocardial ischemia. Circulation. 2011;123:1953–62.

  80. 80.

    Wang Q, Wang L, Wu L, Zhang M, Hu S, Wang R, et al. Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. Sci Rep. 2017;7:45364.

    CAS  Google Scholar 

  81. 81.

    Waldschmidt HV, Homan KT, Cruz-Rodríguez O, Cato MC, Waninger-Saroni J, Larimore KM, et al. Structure-based design, synthesis, and biological evaluation of highly selective and potent G protein-coupled receptor kinase 2 inhibitors. J Med Chem. 2016;59:3793–807.

    CAS  Google Scholar 

  82. 82.

    Nogués L, Reglero C, Rivas V, Neves M, Penela P, Mayor F Jr. G-protein-coupled receptor kinase 2 as a potential modulator of the hallmarks of cancer. Mol Pharmacol. 2017;91:220–8.

    Google Scholar 

  83. 83.

    Mayor F Jr, Cruces-Sande M, Arcones AC, Vila-Bedmar R, Briones AM, Salaices M, et al. G protein-coupled receptor kinase 2 (GRK2) as an integrative signalling node in the regulation of cardiovascular function and metabolic homeostasis. Cell Signal. 2018;41:25–32.

    CAS  Google Scholar 

  84. 84.

    Wei W. Soft regulation of inflammatory immune responses. Chin Pharmacol Bull. 2016;32:297–303.

    Google Scholar 

  85. 85.

    Boyle DL, Soma K, Hodge J, Kavanaugh A, Mandel D, Mease P, et al. The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis. 2015;74:1311–6.

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81673444, 81330081and 81973332).

Author information

Affiliations

Authors

Contributions

Study concept and design: WW and XZY; Writing of the paper: XZY and WW; All authors reviewed the manuscript prior to submission.

Corresponding author

Correspondence to Wei Wei.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yang, Xz., Wei, W. CP-25, a compound derived from paeoniflorin: research advance on its pharmacological actions and mechanisms in the treatment of inflammation and immune diseases. Acta Pharmacol Sin 41, 1387–1394 (2020). https://doi.org/10.1038/s41401-020-00510-6

Download citation

Keywords

  • paeoniflorin-6′-O-benzene sulfonate (CP-25)
  • total glycoside of paeony
  • paeoniflorin
  • inflammation and immune diseases
  • G-protein-coupled receptor kinases 2 (GRK2)

Search

Quick links