Albiflorin alleviates DSS-induced ulcerative colitis in mice by reducing inflammation and oxidative stress

Document Type : Original Article

Authors

1 Department of General Surgery, Bayinguoleng Mongolian Autonomous Prefecture People’s Hospital, Korla, 841000, Xinjiang, China

2 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China

3 Department of General Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215009, Jiangsu, China

Abstract

Objective(s): To clarify therapeutic potential of albiflorin and its intrinsic mechanisms against dextran sulfate sodium (DSS)-induced Ulcerative colitis (UC) mice.
Materials and Methods: Sixty male C57BL/6 mice were randomly divided into five groups: negative control, positive, albiflorin low-dose group, albiflorin high-dose group and treatment control (Salicylazosulfapyridine “SASP”, 100 mg/kg) group. Acute colitis was induced in all groups except NC by administration of 3% DSS for 7 days. Albiflorin and SASP were administered via the intragastric route twice a day for 7 days. The changes of colon tissue were assessed by disease activity index (DAI), HE staining, and ELISA. Adrenodoxin expressions of UC colon tissues were evaluated by immunohistochemistry. Western blotting was performed to investigate related protein of the NF-κB and MAPK signaling pathways. 
Results: It has been found that the albiflorin shares similar influences as the SASP in ameliorating the DSS-induced UC. The reduced DAI and alleviated colon tissue damage were observed in albiflorin intervened groups. Moreover, albiflorin significantly inhibited myeloperoxidase activities and attenuated immuno-inflammatory response and elevated Foxp3 mRNA in colon tissue. Furthermore, investigations revealed that albiflorin could inhibit adrenodoxin isoform and activate activated phosphorylated NF-κB p65 and IκBα, which consequently suppressed phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK).
Conclusion: These findings showed that albiflorin could alleviate DSS-induced murine colitis by activating inhibiting NF-κB and MAPK signaling pathways. It might be a potential therapeutic reagent for UC treatment.

Keywords

References

1. Feuerstein JD, Moss AC, Farraye FA. Ulcerative colitis. Mayo Clin Proc 2019; 94:1357-1373. 
2. Kucharzik T, Koletzko S, Kannengiesser K, Dignass A. Ulcerative colitis-diagnostic and therapeutic algorithms. Dtsch Arztebl Int 2020; 117:564-574. 
3. Neurath MF, Leppkes M. Resolution of ulcerative colitis. Semin Immunopathol 2019; 41:747-756. 
4. Ballester MP, Marti-Aguado D, Fullana M, Bosca-Watts MM, Tosca J, Romero E, et al. Impact and risk factors of non-adherence to 5-aminosalicylates in quiescent ulcerative colitis evaluated by an electronic management system. Int J Colorectal Dis 2019; 34:1053-1059. 
5. Cottone M, Renna S, Modesto I, Orlando A. Is 5-ASA still the treatment of choice for ulcerative colitis? Curr Drug Targets 2011; 12:1396-1405. 
6. Hiraoka S, Fujiwara A, Toyokawa T, Higashi R, Moritou Y, Takagi S, et al. Multicenter survey on mesalamine intolerance in patients with ulcerative colitis. J Gastroenterol Hepatol 2021; 36:137-143. 
7. Huang Y, Wang H, Chen Z, Wang Y, Qin K, Huang Y, et al. Efficacy and safety of total glucosides of paeony combined with methotrexate and leflunomide for active rheumatoid arthritis: a meta-analysis. Drug Des Devel Ther 2019; 13:1969-1984. 
8. Luo J, Song WJ, Xu Y, Chen GY, Hu Q, Tao QW. Benefits and safety of tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviews. Chin J Integr Med 2019; 25:696-703. 
9. Jin L, Li C, Li Y, Wu B. Clinical efficacy and safety of total glucosides of paeony for primary sjogren’s syndrome: a systematic review. Evid Based Complement Alternat Med 2017; 2017:3242301-3242310. 
10. Li R, Zhang JF, Wu YZ, Li YC, Xia GY, Wang LY, et al. Structures and biological evaluation of monoterpenoid glycosides from the roots of paeonia lactiflora. J Nat Prod 2018; 81:1252-1259. 
11. Wang QS, Gao T, Cui YL, Gao LN, Jiang HL. Comparative studies of paeoniflorin and albiflorin from Paeonia lactiflora on anti-inflammatory activities. Pharm Biol 2014; 52:1189-1195. 
12. Sun J, Li X, Jiao K, Zhai Z, Sun D. Albiflorin inhibits the formation of THP-1-derived foam cells through the LOX-1/NF-kappaB pathway. Minerva Med 2019; 110:107-114. 
13. Kim MJ, Kang HH, Seo YJ, Kim KM, Kim YJ, Jung SK. Paeonia lactiflora root extract and its components reduce biomarkers of early atherosclerosis via anti-inflammatory and antioxidant effects in vitro and in vivo. Antioxidants (Basel) 2021; 10:1507-1517. 
14. Xu Y-J, Mei Y, Shi X-Q, Zhang Y-F, Wang X-Y, Guan L, et al. Albiflorin ameliorates memory deficits in APP/PS1 transgenic mice via ameliorating mitochondrial dysfunction. Brain Res 2019; 1719:113-123. 
15. Tan WSD, Liao W, Zhou S, Wong WSF. Is there a future for andrographolide to be an anti-inflammatory drug? deciphering its major mechanisms of action. Biochem Pharmacol 2017; 139:71-81. 
16. Gambhir S, Vyas D, Hollis M, Aekka A, Vyas A. Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies. World J Gastroenterol 2015; 21:3174-3183. 
17. Mitchell S, Vargas J, Hoffmann A. Signaling via the NFκB system. Wiley Interdiscip Rev Syst Biol Med 2016; 8:227-241. 
18. Varthya SB, Sarma P, Bhatia A, Shekhar N, Prajapat M, Kaur H, et al. Efficacy of green tea, its polyphenols and nanoformulation in experimental colitis and the role of non-canonical and canonical nuclear factor kappa beta (NF-kB) pathway: a preclinical in-vivo and in-silico exploratory study. J Biomol Struct Dyn 2021; 39: 5314-5326. 
19. Valmiki S, Ahuja V, Paul J. MicroRNA exhibit altered expression in the inflamed colonic mucosa of ulcerative colitis patients. World J Gastroenterol 2017; 23:5324-5332. 
20. Zhang D-K, Yu J-J, Li Y-M, Wei L-N, Yu Y, Feng Y-H, et al. A picrorhiza kurroa derivative, picroliv, attenuates the development of dextran-sulfate-sodium-induced colitis in mice. Mediators Inflamm 2012; 2012:751629-751638. 
21. Coskun M, Olsen J, Seidelin JB, Nielsen OH. MAP kinases in inflammatory bowel disease. Clinica Chimica Acta 2011; 412:513-520. 
22. Friedman DJ, Künzli BM, A-Rahim YI, Sevigny J, Berberat PO, Enjyoji K, et al. From the cover: CD39 deletion exacerbates experimental murine colitis and human polymorphisms increase susceptibility to inflammatory bowel disease. Proc Natl Acad Sci U S A 2009; 106:16788-16793. 
23. Majumder K, Fukuda T, Zhang H, Sakurai T, Taniguchi Y, Watanabe H, et al. Intervention of isomaltodextrin mitigates intestinal inflammation in a dextran sodium sulfate-induced mouse model of colitis via inhibition of toll-like receptor-4. J Agric Food Chem 2017; 65:810-817. 
24. Du L, Ha C. Epidemiology and pathogenesis of ulcerative colitis. Gastroenterol Clin North Am 2020; 49:643- 654. 
25. Renna S, Cottone M, Orlando A. Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease. World J Gastroenterol 2014; 20:9675-9690. 
26. Lu PD, Zhao YH. Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of chinese medicines. Chin Med 2020; 15:15-26. 
27. Goyal N, Rana A, Ahlawat A, Bijjem KR, Kumar P. Animal models of inflammatory bowel disease: a review. Inflammopharmacology 2014; 22:219-233. 
28. Ewen KM, Ringle M, Bernhardt R. Adrenodoxin--a versatile ferredoxin. IUBMB Life 2012; 64:506-512. 
29. Long Y, Zhao X, Xia C, Li X, Fan C, Liu C, et al. Upregulated IL-17A secretion and CCR6 co-expression in Treg subsets are related to the imbalance of Treg/Th17 cells in active UC patients. Scand J Immunol 2020; 91:12842-12853. 
30. Luo CT, Li MO. Transcriptional control of regulatory T cell development and function. Trends Immunol 2013; 34:531-539. 
31. Ivanov II, Zhou L, Littman DR. Transcriptional regulation of Th17 cell differentiation. Semin Immunol 2007; 19:409- 417. 
32. Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev 2014; 13:3-10. 
33. Dou W, Zhang J, Ren G, Ding L, Sun A, Deng C, et al. Mangiferin attenuates the symptoms of dextran sulfate sodium-induced colitis in mice via NF-κB and MAPK signaling inactivation. Int Immunopharmacol 2014; 23:170-178. 
34. Qian Z, Wu Z, Huang L, Qiu H, Wang L, Li L, et al. Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice. Sci Rep 2015; 5:17348-17361. 
35. Sánchez-Fidalgo S, Villegas I, Rosillo MÁ, Aparicio-Soto M, de la Lastra CA. Dietary squalene supplementation improves DSS-induced acute colitis by downregulating p38 MAPK and NFkB signaling pathways. Mol Nutr Food Res 2015; 59:284-292. 
36. Docena G, Rovedatti L, Kruidenier L, Fanning A, Leakey NAB, Knowles CH, et al. Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease. Clin Exp Immunol 2010; 162:108-115. 
37. Zhang H, Wang J, Lang W, Liu H, Zhang Z, Wu T, et al. Albiflorin ameliorates inflammation and oxidative stress by regulating the NF-κB/NLRP3 pathway in methotrexate-induced enteritis. Int Immunopharmacol 2022; 109:108824.
Iranian Journal of Basic Medical Sciences
Volume 26, Issue 1
January 2023
Pages 48-56

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