Flower extract of Caragana sinica. ameliorates Dss-induced ulcerative colitis by affecting TLR4/NF-κB and TLR4/MAPK signaling pathway in a mouse model

Document Type : Original Article

Authors

1 College of Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, 650500, People’s Republic of China

2 Yunnan Institute of Food Safety, Kunming University of Science and Technology, Kunming, 650500, People’s Republic of China

Abstract

Objective(s): This study aimed to find out the protective effects and preliminary mechanisms of the flower extract of Caragana sinica (FEC) on dextran sulfate sodium salt (DSS)-induced colitis.
Materials and Methods: The ulcerative colitis models of mice induced by 3% DSS were established and treated with FEC. Body weight changes, disease activity index (DAI), colon histopathological score, anti-oxidant ability, and the level of inflammatory cytokines were determined. The expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) were assessed in colonic tissue by immunohistochemical staining. Western blot was used to analyze the expression of TLR4/ nuclear factor kappa-B (NF-κB) and TLR4/ mitogen-activated protein kinase (MAPK) signaling pathway-related proteins.
Results: FEC significantly prevented body weight loss and colonic shortening and reduced the disease activity index and histopathological score (p <0.05). Moreover, FEC treatment remarkably down-regulated the levels of myeloperoxidase (MPO), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) and up-regulated the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and interleukin 10 (IL-10) in the colon of DSS mice (p <0.05). Furthermore, the expression of TLR4/NF-κB and TLR4/MAPK pathway-related proteins was inhibited by FEC (p <0.05).
Conclusion: Our findings demonstrated that FEC could serve as a potential therapeutic agent for treatment of ulcerative colitis.

Keywords

References

1. Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. The Lancet 2017; 389: 1756-1770.
2. Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis? Ann Rheum Dis 2017; 77: 175–187.
3. Petrakis I, Koilakou S, Masouridou K, Kollia AM. Vedolizumab in ulcerative colitis; a budget impact model for a novel drug in a recession environment. Value Health 2015; 18: A622–A623.
4. Kopylov U, Boucher G, Waterman M, Rivers CR, Patel M, Cho JH, et al. Genetic predictors of benign course of ulcerative colitis-A North American inflammatory bowel disease genetics consortium study. Inflamm Bowel Dis 2016; 22: 2311–2316.
5. Xiao B, Merlin D. Oral colon-specific therapeutic approaches toward treatment of inflammatory bowel disease. Expert Opin Drug Deliv 2012; 9: 1393-1407.
6. Yan Y, Ren FL, Wang PC, Sun Y, Xing JF. Synthesis and evaluation of a prodrug of 5-aminosalicylic acid for the treatment of ulcerative colitis. Iran J Basic Med Sci 2019; 22: 1452-1461.
7. Shimodate Y, Takanashi K, Waga E, Fujita T, Katsuki S, Nomura M. Exacerbation of bloody diarrhea as a side effect of mesalamine treatment of active ulcerative colitis. Case Rep Gastroenterol 2011; 5: 159-165.
8. Van Assche G, Manguso F, Zibellini M, Cabriada Nuño JL, Goldis A, Tkachenko E, et al. Corrigendum: Oral prolonged release beclomethasone dipropionate and prednisone in the treatment of active ulcerative colitis: Results from a double-blind, randomized, parallel group study. Am J Gastroenterol 2015; 110: 943.
9. Van Assche G, Manguso F, Zibellini M, Cabriada Nuño JL, Goldis A, Tkachenko E, et al. Oral prolonged release beclomethasone dipropionate and prednisone in the treatment of active ulcerative colitis: results from a double-blind, randomized, parallel group study. Am J Gastroenterol 2015; 110: 708-715.
10. Meng QX, Niu Y, Niu XW, Roubin RH, Hanrahan JR. Ethnobotany, phytochemistry and pharmacology of the genus Caragana used in traditional Chinese medicine. J Ethnopharmacol 2009; 124: 350-368.
11. Liang GL, Bi JB, Huang HQ, Zhang S, Hu CQ. Metabolites and the pharmacokinetics of kobophenol A from Caragana sinica in rats. J Ethnopharmacol 2005; 101: 324-329.
12. Tai ZG, Cai L, Dai L, Sun WJ, Zhe W, Yang YB, et al. Anti-oxidant activities of Caragana sinica flower extracts and their main chemical constituents. Molecules 2010; 15: 6722-6732.
13. Lee SR, Kwak JH, Kim HJ, Pyo S. Neuroprotective effects of kobophenol a against the withdrawal of tropic support, nitrosative stress, and mitochondrial damage in SH-SY5Y neuroblastoma cells. Bioorg Med Chem Lett 2007; 17: 1879–1882.
14. Cho H, Park JH, Ahn EK, Oh JS. Kobophenol a isolated from roots of Caragana sinica (Buc’hoz) rehder exhibits anti-inflammatory activity by regulating NF-κB nuclear translocation in J774A.1 Cells. Toxicol Rep 2018; 5: 647-653.
15. Wang XP, Sun Y, Zhao Y, Ding YX, Zhang XB, Kong LY, et al. Oroxyloside prevents dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB pathway through PPARγ activation. Biochem Pharmacol 2016; 106: 70-81.
16. Shi Z, Li T, Liu YW, Cai TT, Yao WD, Jiang JP, et al. Hepatoprotective and anti-oxidative effects of total flavonoids from Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on nonalcoholic steatohepatitis in vivo and in vitro through Nrf2-ARE signaling pathway. Front Pharmacol 2020; 11: 483-495.
17. Vázquez CV, Rojas MGV, Ramírez CA, Chávez-Servín JL, García-Gasca T, Ferriz Martínez RA, et al. Total phenolic compounds in milk from different species. Design of an extraction technique for quantification using the folin-ciocalteu method. Food Chem 2015; 176: 480-486.
18. Alex P, Zachos NC, Nguyen T, Gonzales L, Chen TE, Conklin LS, et al. Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflamm Bowel Dis 2009; 15: 341-352.
19. Liu W, Guo WJ, Wu J, Luo Q, Tao FF, Gu YH, et al. A novel benzo[d]imidazole derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of NLRP3 inflammasome. Biochem Pharmacol 2013; 85: 1504-1512.
20. Dou W, Zhang JJ, Zhang E, Sun A, Ding LL, Chou GX, et al. Chrysin ameliorates chemically induced colitis in the mouse through modulation of a pxr/nf-κb signaling pathway. J Pharmacol Exp Ther 2013; 345: 473-482.
21. Wang RQ, Wu GT, Du LD, Shao J, Liu FL, Yang ZJ, et al. Semi-bionic extraction of compound turmeric protects against dextran sulfate sodium-induced acute enteritis in rats. J Ethnopharmacol 2016; 190: 288-300.
22. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al.  Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 2001; 22: 153-183.
23. Goyal N, Rana A, Ahlawat A, Bijjem KRV, Kumar P. Animal models of inflammatory bowel disease: a review. Inflammopharmacology 2014; 22: 219-233.
24. Lebeer S, Vanderleyden J, De Keersmaecker SCJ. Host interactions of probiotic bacterial surface molecules: Comparison with commensals and pathogens. Nat Rev Microbiol 2010; 8: 171-184.
25. Guo YL, Wu XX, Wu Q, Lu YF, Shi JS, Chen XP. Dihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice. Toxicol Appl Pharmacol 2018; 344: 35-45.
26. Zhu H, Li YR. Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence. Exp Biol Med (Maywood) 2012; 237: 474-480.
27.    Rezaie A, Parker RD, Abdollahi M. Oxidative stress and pathogenesis of inflammatory bowel disease: an epiphenomenon or the cause? Dig Dis Sci 2007; 52: 2015-2021.
28.    Chen HL, Yang J, Fu YF, Meng XN, Zhao WD, Hu TJ. Effect of total flavonoids of Spatholobus suberectus Dunn on PCV2 induced oxidative stress in RAW264.7 cells. BMC Complement Altern Med 2017; 17: 244-252.
29.    Strengert M, Jennings R, Davanture S, Hayes P, Gabriel G, Knaus UG. Mucosal reactive oxygen species are required for antiviral response: role of Duox in influenza a virus infection. Anti-oxid Redox Signal 2014; 20: 2695-2709.
30. Danese S, Mantovani A. Inflammatory bowel disease and intestinal cancer: A paradigm of the Yin–Yang interplay between inflammation and cancer. Oncogene 2010; 29: 3313-3323.
31. Tian T, Wang ZL, Zhang JH. Pathomechanisms of oxidative stress in inflammatory bowel disease and potential anti-oxidant therapies. Oxid Med Cell Longev 2017; 2017: 1-18.
32. Shen J, Cheng JZ, Zhu SG, Zhao J, Ye QY, Xu YY, et al. Regulating effect of baicalin on IKK/IKB/ NF-κB signaling pathway and apoptosis-related proteins in rats with ulcerative colitis. Int Immunopharmacol 2019; 73: 193-200.
33.    Chavan S, Sava L, Saxena V, Pillai S, Sontakke A, Ingole D. Reduced glutathione: Importance of specimen collection. Indian J Clin Biochem 2005; 20: 150-162.
34. Liu G, Yu L, Fang J, Hu CAA, Yin J, Ni HJ, et al. Methionine restriction on oxidative stress and immune response in DSS-induced colitis mice. Oncotarget 2017; 8: 44511-44520.
35. Xu XP, Zhang L, Liu ZH, Pan Y, Chen D, Yang ZY, et al. Therapeutic efficacy of the traditional chinese medicine baishaoqiwu on TNBS-induced colitis is associated with down-regulation of the TLR4/MyD88/NF-κB signaling pathway. In vivo (Athens, Greece) 2016; 30: 181-196.
36. Slattery ML, Herrick JS, Bondurant KL, Wolff RK. Toll-like receptor genes and their association with colon and rectal cancer development and prognosis. Int J Cancer 2012; 130: 2974-2980.
37. Kumar H, Kawai T, Akira S. Toll-like receptors and innate immunity. Biochem Biophys Res Commun 2009; 388: 621-625.
38. He XX, Wei ZK, Wang JJ, Kou JH, Liu WJ, Fu YH, et al. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis. Sci Rep 2016; 6: 28370-28380.
39. Choi YH, Bae JK, Chae HS, Choi YO, Nhoek P, Choi JS, et al. Isoliquiritigenin ameliorates dextran sulfate sodium-induced colitis through the inhibition of MAPK pathway. Int Immunopharmacol 2016; 31: 223-232.
40. Park JH, Peyrin-Biroulet L, Eisenhut M, Shin JI. IBD immunopathogenesis: A comprehensive review of inflammatory molecules. Autoimmun Rev 2017; 16: 416-426.
41. Perkins ND. Integrating cell-signalling pathways with NF-κB and IKK function. Nat Rev Mol Cell Biol 2007; 8: 49-62.
42. Oh WJ, Jung U, Eom HS, Shin HJ, Park HR. Inhibition of lipopolysaccharide-induced proinflammatory responses by Buddleja officinalis extract in BV-2 microglial cells via negative regulation of NF-κB and ERK1/2 signaling. Molecules 2013; 18: 9195-9206.
43. Thalhamer T, McGrath MA, Harnett MM. MAPKs and their relevance to arthritis and inflammation. Rheumatology 2007; 47: 409-414.
44. Li CP, Li JH, He SY, Chen O, Shi L. Effect of curcumin on p38MAPK expression in DSS-induced murine ulcerative colitis. Genet Mol Res 2015; 14: 3450-3458.
45. Saccani S, Pantano S, Natoli G. p38-dependent marking of inflammatory genes for increased NF-κB recruitment. Nat Immunol 2001; 3: 69-75.
46. Min GY, Park JM, Joo IH, Kim DH. Inhibition effect of Caragana sinica root extracts on Osteoarthritis through MAPKs, NF-κB signaling pathway. Int J Med Sci 2021;18: 861-872.
47. Wu WL, Li DY, Zong Y, Zhu H, Pan DF, Xu TD, et al. Luteolin inhibits inflammatory responses via p38/MK2/TTP-mediated mRNA stability. Molecules 2013; 18: 8083-8094.
48. Seelinger G, Merfort I, Schempp CM. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med 2008; 74: 1667-1677.
49. Han YM, Koh J, Kim JH, Lee J, Im JP, Kim JS. Astragalin inhibits nuclear factor-κb signaling in human colonic epithelial cells and attenuates experimental colitis in mice. Gut Liver 2021; 15: 100-108.
50. Mascaraque C, González R, Suárez MD, Zarzuelo A, de Medina FS, Martínez-Augustin O. Intestinal anti-inflammatory activity of apigenin K in two rat colitis models induced by trinitrobenzenesulfonic acid and dextran sulphate sodium. Br J Nutr 2015; 113: 618-626.
51. Sun LC, Zhang HB, Gu CD, Guo SD, Li G, Lian R, et al. Protective effect of acacetin on sepsis-induced acute lung injury via its anti-inflammatory and anti-oxidative activity. Arch Pharm Res 2018; 41: 1199-1210.
Iranian Journal of Basic Medical Sciences
Volume 24, Issue 5
May 2021
Pages 595-603

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