Effects of nitidine chloride on ulcerative colitis in mice and its mechanism

doi:10.12047/j.cjap.5827.2019.115

Abstract

Abstract: Objective: To investigate the protective effects of nitidine chloride (NC) on dextran sodium sulfate (DSS) - induced ulcerative colitis (UC) in mice by targeting miR-31 and its underlying mechanisms. Methods: DSS at the concentration of 1% was used to induce UC in mice. Thirty C57BL/6 male mice were randomly divided into four groups: normal control group (n=7), DSS group (n=8), DSS + NC group (7.27 mg/kg) (n=8) and NC group (n=7). DSS was added in drinking water, and NC was administrated by gavage. The period of modeling lasted for 3 weeks. The control group and NC group drank sterile water every day, DSS group and DSS + NC group drank 1% DSS water in the first week, normal water in the second week and 1% DSS water in the third week. In the last week of modeling, mice in control group and DSS group were given 0.5% CMC-Na by gavage, while mice in DSS + NC group and NC group were given NC by gavage. After the establishment of the model, the disease activity index (DAI) related to colitis was observed, the pathological score of colon tissue was evaluated by HE staining, the expression level of miR-31 in colon tissue was detected by qPCR, and the protein expressions of NF -κ B and COX-2 in colon tissue were detected by Western blot. Results: ① Compared with DSS group, the DAI in the DSS + NC group was decreased (P＜0.01). The colonic pathological injury was obviously ameliorated after treated by NC. ② Compared with normal control group, the expression of miR-31 in colonic tissue of DSS group was increased significantly(P＜0.01), compared with DSS group, the expression of miR-31 was decreased after treatment with NC(P＜ 0.05). ③ Compared with DSS group, the levels of inflammatory protein NF-κB and COX-2 in DSS + NC group was decreased significantly (P＜0.05). Conclusion: Nitidine chloride has obvious therapeutic effects on DSS induced mouse colitis, and its anti-inflammatory mechanism is related to the down-regulation of miR-31 expression.

Key words: nitidine chloride, miR-31, ulcerative colitis, NF-<sub>k</sub>B

CLC Number:

R333.3

WU Ya-li, LIU Xin, LIU Kai-li, CUI Xiang-li, WANG Chun-fang. Effects of nitidine chloride on ulcerative colitis in mice and its mechanism[J]. CJAP, 2019, 35(6): 525-529.

References

[1] Ramos GP, Papadakis KA. Mechanisms of disease: inflammatory bowel diseases[J]. Mayo Clin Proc, 2019, 94(1): 155-165.
[2] Huang YF, Zhou JT, Qu C, et al. Anti-inflammatory effects of Brucea javanica oil emulsion by suppressing NF-κB activation on dextran sulfate sodium-induced ulcerative colitis in mice[J]. J Ethnopharmacol, 2017, 198: 389-398.
[3] Hilsden Rj, Verhoef Mj, Best A, et al. Complementary and alternative medicine use by Canadian patients with inflammatory bowel disease: results from a national survey[J]. Am J Gastroenterol, 2003, 98(7): 1563-1568.
[4] Head K, Jurenka JS. Crohn's disease—pathophysiology and conventional and alternative treatment options [J]. Altern Med Rev, 2004, 9(4): 360-401.
[5] Khan H, Hadda TB, Touzani R. Diverse therapeutic potential of nitidine, a comprehensive review[J]. Curr Drug Metab, 2018, 19: 986-991.
[6] Chen WX, Ren LH, Shi RH. Implication of miRNAs for inflammatory bowel disease treatment: Systematic review[J]. World J Gastrointest Pathophysiol, 2014, 5(2): 63-70.
[7] Wang ZQ, Wei Jiang, Zhi Zhang, et al. Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF- kappa B pathway in RAW 264.7 cells[J]. J Ethnopharmacol, 2012, 144(1): 145-150.
[8] Seril DN, Liao J, Yang GY, et al. Oxidative stress and ulcerative colitis associated carcinogenesis: studies in humans and animal models[J]. Carcinogenesis, 2003, 24(3): 353-362.
[9] Murano M, Maemura K, Hirata I, et al. Therapeutic effect of intracolonically administered nuclear factor κ B (p65) antisense oligonucleotide on mouse dextran sulphate sodium(DSS)-induced colitis [J]. Clin Exp Immunol, 2000, 120 (1): 51-58.
[10]Wang J, Chen J, Sen S. MicroRNA as Biomarkers and Diagnostics[J]. J Cell Physiol, 2016, 231(1): 25-30.
[11]Dong Q, Li C, Che X, et al. MicroRNA-891b is an independent prognostic factor of pancreatic cancer by targeting Cbl-b to suppress the growth of pancreatic cancer cells[J]. Oncotarget, 2016, 7(50): 82338-82353.
[12]Greco S, Fansanaro P, Castelvecchio S, et al. MicroRNA dysregulation in diabetic ischemic heart failure patients[J]. Diabetes, 2012, 61(6): 1633-1641.
[13]Cao B, Zhou X, Ma J, et al. Role of MiRNAs in inflammatory bowel disease[J]. Dig Dis Sci, 2017, 62(6): 1426-1438.
[14]Bardua M, Haftmann C, Durek P, et al. MicroRNA-31 reduces the motility of proinflammatory T helper 1 lymphocytes[J]. Front Immunol, 2018, 9: 2813.
[15]Sebastiani G, Nigi L, Spagnuolo L, et al. MicroRNA profiling in sera of patients with type 2 diabetes mellitus reveals an upregulation of miR-31 expression in subjects with microvascular complications[J]. J Biomed Sci Engineering, 2013, 6: 58-64.
[16]Wang HW, Huang TS, Lo HH, et al. Deficiency of the microRNA-31-microRNA-720 pathway in the plasma and endothelial progenitor cells from patients with coronary artery disease[J]. Arterioscler Thromb Vasc Biol, 2014, 34(4): 857-869.
[17]Chapman CG, Pekow J. The emerging role of miRNAs in inflammatory bowel disease: A review[J]. Ther Adv Gastroenterol, 2015, 8(1): 4-22.
[18]Coskun M, Bjerrum JT, Seidelin JB, et al. MicroRNAs in inflammatory bowel disease—pathogenesis,diagnostics and therapeutics[J]. World J Gastroenterol, 2012, 18(34): 4629-4634.
[19]Fisher K, Lin J. MicroRNA in inflammatory bowel disease: Translational research and clinical implication[J]. World J Gastroenterol, 2015, 21(43): 12274-12282.
[20]Schaefer JS, Attumi T, Opekun AR, et al. MicroRNA signatures differentiate Crohn’s disease from ulcerative colitis[J]. BMC Immunol, 2015, 16: 5.
[21]Wu F, Zikusoka M, Trindade A, et al. MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2α[J]. Gastroenterology, 2008, 135(5): 1624-1635.
[22]王茜, 张钧栋, 刘鑫, 等. 白藜芦醇通过G2期阻滞抑制结肠癌细胞的增殖[J].中国中西医结合消化杂志, 2018, 26(2): 161-171.
[23] Xu N, Meisgen F, Butler LM, et al. MicroRNA-31 is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting serine/threonine kinase 40[J]. J Immuno, 2013, 190(2): 678-688.