Anti-inflammatory Effects and Mechanisms of Rhein, an Anthraquinone Compound, and Its Applications in Treating Arthritis: A Review

doi:10.1007/s13659-020-00272-y

应用天然产物 ›› 2020, Vol. 10 ›› Issue (6): 445-452.DOI: 10.1007/s13659-020-00272-y

Anti-inflammatory Effects and Mechanisms of Rhein, an Anthraquinone Compound, and Its Applications in Treating Arthritis: A Review

Hongjuan Wang¹, Dezhi Yang¹, Li Li², Shiying Yang¹, Guanhua Du², Yang Lu^1,2

1 Beijing Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
2 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

收稿日期:2020-08-02 修回日期:2020-10-12 出版日期:2020-12-24 发布日期:2020-12-24
通讯作者: Yang Lu
基金资助:
This work was financially supported by Drug Innovation Major Project (Grant Nos. 2018ZX09711001-001-015, 2018ZX09711001-003-022) and CAMS Innovation Fund for Medical Sciences (Grant No. 2016-I2M-3-007).

Anti-inflammatory Effects and Mechanisms of Rhein, an Anthraquinone Compound, and Its Applications in Treating Arthritis: A Review

Hongjuan Wang¹, Dezhi Yang¹, Li Li², Shiying Yang¹, Guanhua Du², Yang Lu^1,2

1 Beijing Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
2 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

Received:2020-08-02 Revised:2020-10-12 Online:2020-12-24 Published:2020-12-24
Contact: Yang Lu
Supported by:
This work was financially supported by Drug Innovation Major Project (Grant Nos. 2018ZX09711001-001-015, 2018ZX09711001-003-022) and CAMS Innovation Fund for Medical Sciences (Grant No. 2016-I2M-3-007).

摘要/Abstract

摘要： Inflammation is a defensive response of living tissues to damaging agents, which exists in two forms, acute inflammation and chronic inflammation, and chronic inflammation is closely related to arthritis. Currently, the commonly prescribed antiinflammatory medications are greatly limited by high incidence of gastrointestinal erosions in the clinical applications. Rhein, a bioactive constituent of anthraquinone, exhibits excellent anti-inflammatory activities and therapeutic effects on arthritis with less gastrointestinal damages. Although there are numbers of studies on anti-inflammatory effects and mechanisms of rhein in the last few decades, to the best of our knowledge, only a few review articles pay attention to the interactive relationships of rhein on multiple inflammatory signaling pathways and cellular processes from a comprehensive perspective. Herein, we summarized anti-inflammatory effects and mechanisms of rhein and its practical applications in the treatment of arthritis, thereby providing a reference for its basic researches and clinical applications.

关键词: Rhein, Anthraquinone, Anti-inflammatory, Arthritis

Abstract: Inflammation is a defensive response of living tissues to damaging agents, which exists in two forms, acute inflammation and chronic inflammation, and chronic inflammation is closely related to arthritis. Currently, the commonly prescribed antiinflammatory medications are greatly limited by high incidence of gastrointestinal erosions in the clinical applications. Rhein, a bioactive constituent of anthraquinone, exhibits excellent anti-inflammatory activities and therapeutic effects on arthritis with less gastrointestinal damages. Although there are numbers of studies on anti-inflammatory effects and mechanisms of rhein in the last few decades, to the best of our knowledge, only a few review articles pay attention to the interactive relationships of rhein on multiple inflammatory signaling pathways and cellular processes from a comprehensive perspective. Herein, we summarized anti-inflammatory effects and mechanisms of rhein and its practical applications in the treatment of arthritis, thereby providing a reference for its basic researches and clinical applications.

Key words: Rhein, Anthraquinone, Anti-inflammatory, Arthritis

Hongjuan Wang, Dezhi Yang, Li Li, Shiying Yang, Guanhua Du, Yang Lu. Anti-inflammatory Effects and Mechanisms of Rhein, an Anthraquinone Compound, and Its Applications in Treating Arthritis: A Review[J]. 应用天然产物, 2020, 10(6): 445-452.

参考文献

1. O. Takeuchi, S. Akira, Cell 140, 805-820 (2010)
2. C. Gabay, I. Kushner, N. Engl. J. Med. 340, 448-454 (1999)
3. T. Tamura, T. Shirai, N. Kosaka, K. Ohmori, N. Takafumi, Eur. J. Pharmacol. 448, 81-87 (2002)
4. D. Hürlimann, F. Enseleit, F. Ruschitzka, Herz 29, 760-768 (2004)
5. M.A. González-Gay, C. González-Juanatey, Arthritis Res. Ther. 14, 122 (2012)
6. S.E. Sweeney, G.S. Firestein, Int. J. Biochem. Cell Biol. 36, 372-378 (2004)
7. I.B. Mcinnes, G. Schett, Nat. Rev. Immunol. 7, 429-442 (2007)
8. P. Libby, Am. J. Med. 121, S21-S31 (2008)
9. M.J. Benito, D.J. Veale, O. Fitzgerald, W.B.V.D. Berg, B. Bresnihan, Ann. Rheum. Dis. 64, 1263-1267 (2005)
10. J. Sellam, F. Berenbaum, Nat. Rev. Rheumatol. 6, 625 (2010)
11. S. Vilá, Puerto Rico Health Ences J. 36, 123-129 (2017)
12. N. Schlesinger, Drugs 64, 2399-2416 (2004)
13. C.A. Dinarello, L.A.B. Joosten, Nat. Rev. Rheumatol. 12, 78-80 (2016)
14. S. Chu, S. Yang, K. Lue, Y. Hsieh, T. Hsiao, K. Lu, Clin. Chim. Acta 339, 77-83 (2004)
15. H. Chen, S. Zheng, Y. Wang, H. Zhu, Q. Liu, Y. Xue, J. Qiu, H. Zou, X. Zhu, Clin. Rheumatol. 35, 1189-1195 (2014)
16. C. Cuvelier, C. Barbatis, H. Mielants, M. De Vos, H. Roels, E.M. Veys, Gut 28, 394-401 (1987)
17. J.R. Vane, R.M. Botting, Inflamm. Res. 47, 78-87 (1998)
18. B. Cryer, M. Feldman, Am. J. Med. 104, 413-421 (1998)
19. I. Bjarnason, J. Hayllar, A. Macpherson, A.S. Russell, Gastroenterology 104, 1832-1847 (1993)
20. N.E. Quintana, A.R. Allocco, J.A. Ponce, M.G. Magurno, Clin. Ophthalmol. 8, 1209-1212 (2014)
21. S. Samieirad, H. Afrasiabi, E. Tohidi, M. Qolizade, B. Shaban, M.A. Hashemipour, I.D. Shirvan, J. Cranio-Maxillofac. Surg. 45, 1614-1621 (2017)
22. Y. Yuan, I.T. Padol, R.H. Hunt, Nat. Clin. Pract. Gastroenterol. Hepatol. 3, 80-89 (2006)
23. Y.K. Shim, N. Kim, Korean J. Gastroenterol. 67, 300-312 (2016)
24. A.B. Ballinger, G.V. Smith, Expert Opin. Pharmacother. 2, 31-40 (2001)
25. F.L. Lanza, F.K.L. Chan, E.M. Quigley, Am. J. Gastroenterol. 104, 728-738 (2009)
26. W. Chang, M. Chu, C. Hsu, Y.J. Wu, J. Lee, T. Chen, W. Chung, D. Chen, S. Hung, Am. J. Chin. Med. 47, 135-151 (2019)
27. H. Sun, G. Luo, D. Chen, Z. Xiang, Front. Pharmacol. 7, 247 (2016)
28. S. Zhuang, J. Zhong, Q. Zhou, Y. Zhong, P. Liu, Z. Liu, Int. Immunopharmacol. 71, 321-327 (2019)
29. T. Tamura, K. Ohmori, Jpn. J. Pharmacol. 85, 101-104 (2001)
30. G. Martin, P. Bogdanowicz, F. Domagala, H. Ficheux, J.P. Pujol, Biorheology 41, 549-561 (2004)
31. F. Moldovan, J.P. Pelletier, F.C. Jolicoeur, J.M. Cloutier, J. Martelpelletier, Osteoarthr. Cartil. 8, 186-196 (2000)
32. M.V.C. Nguyen, M. Dougados, L. Berdah, B. Amor, Arthritis Rheum. 37, 529-536 (1994)
33. J. Martelpelletier, F. Mineau, F.C. Jolicoeur, J.M. Cloutier, J.P. Pelletier, J. Rheumatol. 25, 753-762 (1998)
34. F. Legendre, P. Bogdanowicz, G. Martin, F. Domagala, S. Leclercq, J.P. Pujol, H. Ficheux, Clin. Exp. Rheumatol. 25, 546-555 (2007)
35. J. Cai, Y. Duan, J. Yu, J. Chen, M. Chao, M. Ji, Eur. J. Med. Chem. 55, 409-419 (2012)
36. C. Wu, H. Cao, H. Zhou, L. Sun, J. Xue, J. Li, Y. Bian, R. Sun, S. Dong, P. Liu, Anticancer Agents Med. Chem. 15, 1624-1632 (2015)
37. G.B. Porro, S. Ardizzone, I. Caruso, F. Montrone, Minerva Med. 78, 411-413 (1987)
38. F. Legendre, A. Heuze, K. Boukerrouche, S. Leclercq, K. Boumediene, P. Galera, F. Domagala, J.P. Pujol, H. Ficheux, Scand. J. Rheumatol. 38, 104-111 (2009)
39. N. Samnang, N. Pavel, K. Ladislav, Chemotherapy 59, 447-452 (2013)
40. Z. Meng, Y. Yan, Z. Tang, C. Guo, N. Li, W. Huang, G. Ding, Z. Wang, W. Xiao, Z. Yang, Planta Med. 81, 279-285 (2015)
41. Y. Gao, X. Chen, L. Fang, F. Liu, R. Cai, C. Peng, Y. Qi, Free Radic. Biol. Med. 72, 104-112 (2014)
42. A.F. Mendes, M.M. Caramona, A.P.D. Carvalho, M.C. Lopes, Pharmacol. Toxicol. 91, 22-28 (2002)
43. J. Cuschieri, R.V. Maier, Crit. Care Med. 33, 417-419 (2005)
44. A.S. Kamiguti, R.J. Harris, J.R. Slupsky, P.K. Baker, J.C. Cawley, M. Zuzel, Oncogene 22, 2272-2284 (2003)
45. S. Lin, J.J. Li, M. Fujii, D. Hou, Int. J. Oncol. 22, 829-833 (2003)
46. C.G. Lee, H. Link, P. Baluk, R.J. Homer, S.P. Chapoval, V. Bhandari, M. Kang, L. Cohn, Y.K. Kim, D. Mcdonald, Nat. Med. 10, 1095-1103 (2004)
47. Z. He, R. Zhou, M. He, C.B. Lau, G.G. Yue, W. Ge, P.P. But, Phytomedicine 18, 470-478 (2011)
48. V.E. Fernand, J.N. Losso, R.E. Truax, E.E. Villar, D.K. Bwambok, S.O. Fakayode, M. Lowry, I.M. Warner, Chem. Biol. Interact. 192, 220-232 (2011)
49. Y. Han, S.H. Lee, I.S. Lee, K.Y. Lee, Food Chem. Toxicol. 106, 17-24 (2017)
50. P. Antonisamy, P. Agastian, C. Kang, N. Kim, J.H. Kim, Saudi J. Biol. Sci. 26, 96-104 (2017)
51. E. Mortaz, I.M. Adcock, H. Shafei, M.R. Masjedi, G. Folkerts, Tanaffos 11, 6-11 (2012)
52. F. Hu, F. Xing, G. Zhu, G. Xu, C. Li, J. Qu, I. Lee, L. Pan, Sci. Rep. 5, 14012-14012 (2015)
53. J.W.J. Bijlsma, F. Berenbaum, F.P.J.G. Lafeber, The Lancet 377, 2115-2126 (2011)
54. T. Hayami, M. Pickarski, Y. Zhuo, G. Wesolowski, G.A. Rodan, L.T. Duong, Bone 38, 234-243 (2006)
55. A.B. Blom, S.M. Brockbank, P.L.E.M. Van Lent, H.M. Van Beuningen, J. Geurts, N. Takahashi, P.M.V. Der Kraan, F.A.J.V. De Loo, B.W. Schreurs, K.M. Clements, Arthritis Rheum. 60, 501-512 (2009)
56. J.C. Fernandes, G. Tardif, J. Martelpelletier, V. Lascaucoman, M. Dupuis, F. Moldovan, M. Sheppard, B.R. Krishnan, J. Pelletier, Am. J. Pathol. 154, 1159-1169 (1999)
57. R.K. Studer, D. Jaffurs, M. Stefanovicracic, P.D. Robbins, C.H. Evans, Osteoarthr. Cartil. 7, 377-379 (1999)
58. M. Yaron, I. Shirazi, I. Yaron, Osteoarthr. Cartil. 7, 272-280 (1999)
59. I.B. Mcinnes, G. Schett, N. Engl. J. Med. 365, 2205-2219 (2011)
60. J.A.D.S. Jaques, L.V. Becker, V.D.C.G. Souza, C.A.M. Leal, T.M.D. Bertoldo, K.D.V. Pinheiro, V.M. Morsch, M.R.C. Schetinger, D.B.R. Leal, Cell Biochem. Funct. 31, 395-399 (2013)
61. F. Hu, D. Zhu, W. Pei, I. Lee, X. Zhang, L. Pan, J. Xu, Int. Immunopharmacol. 75, 105780 (2019)
62. G. Martin, P. Bogdanowicz, F. Domagala, H. Ficheux, J. Pujol, Inflammation 27, 233-246 (2003)
63. N. Zippel, R.A. Malik, T. Fromel, R. Popp, E. Bess, B. Strilic, N. Wettschureck, I. Fleming, B. Fisslthaler, Arterioscler. Thromb. Vasc. Biol. 33, 2792-2799 (2013)
64. L.O. Demirezer, M. Bodur, Planta Med. 81, PM_170 (2015)
65. N. Schlesinger, R.G. Thiele, Ann. Rheum. Dis. 69, 1907-1912 (2010)
66. S.R. Kingsbury, P.G. Conaghan, M.F. Mcdermott, J. Inflamm. Res. 4, 39-49 (2011)
67. F.A. Amaral, V.V. Costa, L.D. Tavares, D. Sachs, M.M. Teixeira, Arthritis Rheumatol. 64, 474-484 (2012)
68. F.A. Amaral, L.F.S. Bastos, T.H.C. Oliveira, A.C.F. Dias, V.L.S. De Oliveira, L.D. Tavares, V.V. Costa, I. Galvao, F.M. Soriani, D.E. Szymkowski, Eur. J. Immunol. 46, 204-211 (2016)
69. M.I. Santos, R.L. Reis, Macromol. Biosci. 10, 12-27 (2010)
70. X. Xu, X. Qi, Y. Yan, J. Qi, N. Qian, L. Guo, C. Li, F. Wang, P. Huang, H. Zhou, Eur. J. Med. Chem. 123, 769-776 (2016)
71. J.P. Pelletier, D. Lajeunesse, P. Reboul, F. Mineau, J. MartelPelletier, J. Rheumatol. 28, 814 (2001)

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Anti-inflammatory Effects and Mechanisms of Rhein, an Anthraquinone Compound, and Its Applications in Treating Arthritis: A Review

Anti-inflammatory Effects and Mechanisms of Rhein, an Anthraquinone Compound, and Its Applications in Treating Arthritis: A Review

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