Abstract
Ulcerative colitis is a serious intestinal disorder, which can lead to a variety of complications, and in severe cases, the risk of becoming cancerous, seriously harming human health. This study aimed to investigate the anti-inflammatory effect of shionone on ulcerative colitis and analyze its potential mechanism of action. Cell counting kit-8 and lactate dehydrogenase kits were used to detect the viability of colorectal adenocarcinoma Caco-2 cells and lactate dehydrogenase activity, respectively. Apoptosis of the treated cells was detected using flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins and p38 MAPK/NF-κB signaling pathway-related proteins. Changes in inflammatory factor secretion in cell supernatants were detected using enzyme-linked immunosorbent assay. Shionone showed no toxic effects on the cells. Shionone enhanced the proliferative activity of lipopolysaccharide-induced Caco-2 cells, decreased lactate dehydrogenase activity, and reduced apoptosis. It also suppressed the secretion of inflammatory factors. Shionone was found to affect the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway by decreasing the expression levels of p-p38 and p-p65 proteins and decreasing the ratio of p-p38/p38 and p-p65/p65. Moreover, the p38 mitogen-activated protein kinase agonist, P79350, significantly reversed the effects of shionone on lipopolysaccharide-induced Caco-2 cells, as demonstrated by the promotion of the expression of p-p38 and p-p65, the elevation of the p-p38/p38 and p-p65/p65 ratios, an increase in cell apoptosis, and an increase in inflammatory factor secretion. Shionone alleviated ulcerative colitis through the p38 MAPK/NF-κB signaling pathway, providing a novel therapeutic target for the management of ulcerative colitis.
Graphical Abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Aldars-García L, Marin AC, Chaparro M, Gisbert JP (2021) The interplay between immune system and microbiota in inflammatory bowel disease: a narrative review. Int J Mol Sci 22:3076. https://doi.org/10.3390/ijms22063076
Althagafy HS, Ali FEM, Hassanein EHM, Mohammedsaleh ZM, Kotb El-Sayed MI, Atwa AM, Sayed AM, Soubh AA (2023) Canagliflozin ameliorates ulcerative colitis via regulation of TLR4/MAPK/NF-kappaB and Nrf2/PPAR-gamma/SIRT1 signaling pathways. Eur J Pharmacol 960:176166. https://doi.org/10.1016/j.ejphar.2023.176166
Ansari MN, Rehman NU, Karim A, Soliman GA, Ganaie MA, Raish M, Hamad AM (2021) Role of oxidative stress and infammatory cytokines (TNF-α and IL-6) in acetic acid-induced ulcerative colitis in rats: ameliorated by Otostegia fruticosa. Life 11:195. https://doi.org/10.3390/life11030195
Athari SS (2019) Targeting cell signaling in allergic asthma. Signal Transduct Target Ther 4:45. https://doi.org/10.1038/s41392-019-0079-0
Chen H, Tao L, Liang J, Pan C, Wei H (2023) Ubiquitin D promotes the progression of rheumatoid arthritis via activation of the p38 MAPK pathway. Mol Med Rep 27:53. https://doi.org/10.3892/mmr.2023.12940
Davis SC, Robinson BL, Vess J, Lebel JS (2018) Primary care management of ulcerative colitis. Nurse Pract 43:11–19. https://doi.org/10.1097/01.NPR.0000527565.05934.14
Dönder Y, Arikan TB, Baykan M, Akyüz M, Öz AB (2018) Effects of quercitrin on bacterial translocation in a rat model of experimental colitis. Asian J Surg 41:543–550. https://doi.org/10.1016/j.asjsur.2017.12.002
Dong LN, Wang M, Guo J, Wang JP (2019) Influences of probiotics combined with sulfasalazine on rats with ulcerative colitis via the Wnt/β-catenin signaling pathway. Eur Rev Med Pharmacol Sci 23:6371–6378. https://doi.org/10.26355/eurrev_201907_18461
Du H, Zhang M, Yao K, Hu Z (2017) Protective effect of Aster tataricus extract on retinal damage on the virtue of its antioxidant and anti-inflammatory effect in diabetic rat. Biomed Pharmacother 89:617–622. https://doi.org/10.1016/j.biopha.2017.01.179
Du R, Wang T, Lv H, Zou Y, Hou X, Hou N, Zhang P, Li H, Chi G (2022) Shionone-targeted pneumolysin to ameliorate acute lung injury induced by Streptococcus pneumoniae in vivo and in vitro. Molecules 27:6258. https://doi.org/10.3390/molecules27196258
Elkholy SE, Maher SA, Abd El-Hamid NR, Elsayed HA, Hassan WA, Abdelmaogood AKK, Hussein SM, Jaremko M, Alshawwa SZ, Alharbi HM, Imbaby S (2023) The immunomodulatory effects of probiotics and azithromycin in dextran sodium sulfate-induced ulcerative colitis in rats via TLR4-NF-κB and p38-MAPK pathway. Biomed Pharmacother 165:115005. https://doi.org/10.1016/j.biopha.2023.115005
Huang P, Bai L, Liu L, Fu J, Wu K, Liu H, Liu Y, Qi B, Qi B (2021) Redd1 knockdown prevents doxorubicin-induced cardiac senescence. Aging 13:13788–13806. https://doi.org/10.18632/aging.202972
Keefer L, Bedell A, Norton C, Hart AL (2022) How should pain, fatigue, and emotional wellness be incorporated into treatment goals for optimal management of inflammatory bowel disease? Gastroenterology 162:1439–1451. https://doi.org/10.1053/j.gastro.2021.08.060
Kobayashi T, Siegmund B, Le Berre C, Wei SC, Ferrante M, Shen B, Bernstein CN, Danese S, Peyrin-Biroulet L, Hibi T (2020) Ulcerative Colitis Nat Rev Dis Primers 6:74. https://doi.org/10.1038/s41572-020-0205-x
Li C, Lun WJ, Zhao XM, Lei S, Guo YD, Ma J, Zhi FC (2015) Allicin alleviates inflammation of trinitrobenzenesulfonic acid-induced rats and suppresses P38 and JNK pathways in Caco-2 cells. Mediators Inflamm 2015:434692. https://doi.org/10.1155/2015/434692
Li J, Zheng M, Wang C, Jiang J, Xu C, Li L, Li L, Yan G, Jin Y (2020a) Cryptotanshinone attenuates allergic airway inflammation through negative regulation of NF-κB and p38 MAPK. Biosci Biotechnol Biochem 84:268-278. https://doi.org/10.1080/09168451.2019.1687280
Li J, Tang RS, Shi Z, Li JQ (2020b) Nuclear factor-kappaB in rheumatoid arthritis. Int J Rheum Dis 23:1627-1635. https://doi.org/10.1111/1756-185X.13958
Liu Y, Huang ZZ, Min L, Li ZF, Chen K (2021) The BRD4 inhibitor JQ1 protects against chronic obstructive pulmonary disease in mice by suppressing NF-kappaB activation. Histol Histopathol 36:101–112. https://doi.org/10.14670/HH-18-283
Luo Y, Yu MH, Yan YR, Zhou Y, Qin SL, Huang YZ, Qin J, Zhong M (2020) Rab27A promotes cellular apoptosis and ROS production by regulating the miRNA-124-3p/STAT3/RelA signalling pathway in ulcerative colitis. J Cell Mol Med 24:11330–11342. https://doi.org/10.1111/jcmm.15726
Mu PW, Jiang P, Wang MM, Chen YM, Zheng SH, Tan Z, Jiang W, Zeng LY, Wang TH (2016) Oestrogen exerts anti-inflammation via p38 MAPK/NF-κB cascade in adipocytes. Obes Res Clin Pract 10:633–641. https://doi.org/10.1016/j.orcp.2016.02.007
Pelaia C, Vatrella A, Gallelli L, Lombardo N, Sciacqua A, Savino R, Pelaia G (2021) Role of p38 mitogen-activated protein kinase in asthma and COPD: pathogenic aspects and potential targeted therapies. Drug Des Devel Ther 15:1275–1284. https://doi.org/10.2147/DDDT.S300988
Prescott JA, Mitchell JP, Cook SJ (2021) Inhibitory feedback control of NF-kappaB signalling in health and disease. Biochem J 478:2619–2664. https://doi.org/10.1042/BCJ20210139
Samman FS, Elaidy SM, Essawy SS, Hassan MS (2018) New insights on the modulatory roles of metformin or alpha-lipoic acid versus their combination in dextran sulfate sodium-induced chronic colitis in rats. Pharmacol Rep 70:488–496. https://doi.org/10.1016/j.pharep.2017.11.015
Sanz-Ezquerro JJ, Cuenda A (2021) p38 signalling pathway. J Mol Sci 22:1003. https://doi.org/10.3390/ijms22031003
Segal JP, LeBlanc JF, Hart AL (2021) Ulcerative colitis: an update. Clin Med 21:135–139. https://doi.org/10.7861/clinmed.2021-0080
Wang X, Fan L, Yin H, Zhou Y, Tang X, Fei X, Tang H, Peng J, Ren X, Xue Y, Zhu C, Luo J, Jin Q, Jin Q (2020) Protective effect of Aster tataricus extract on NLRP3-mediated pyroptosis of bladder urothelial cells. J Cell Mol Med 24:13336–13345. https://doi.org/10.1111/jcmm.15952
Wang X, Yin H, Fan L, Zhou Y, Tang X, Fei X, Tang H, Peng J, Zhang J, Xue Y, Luo J, Jin Q, Jin Q (2021) Shionone alleviates NLRP3 inflammasome mediated pyroptosis in interstitial cystitis injury. Int Immunopharmacol 90:107132. https://doi.org/10.1016/j.intimp.2020.107132
Wang H, Teng J, Wang M, Zhang Y, Liu X, Liu Z (2023) Expression and significant roles of the lncRNA NEAT1/miR-493-5p/Rab27A axis in ulcerative colitis. Immun Inflamm Dis 11:e814. https://doi.org/10.1002/iid3.814
Whitaker RH, Cook JG (2021) Stress relief techniques: p38 MAPK determines the balance of cell cycle and apoptosis pathways. Biomolecules 11:1444. https://doi.org/10.3390/biom11101444
Xu N, Hu J, Han K, Ou Y, Ji T, Xing J (2020) Shionone suppresses the growth, migration and invasion of human breast cancer cells via induction of apoptosis and inhibition of MEK/ERK and STAT3 signalling pathways. J BUON 25:1821–1826
Yang L, Shen L, Li Y, Li Y, Yu S, Wang S (2017) Hyperoside attenuates dextran sulfate sodium-induced colitis in mice possibly via activation of the Nrf2 signalling pathway. J Inflamm 14:25. https://doi.org/10.1186/s12950-017-0172-5
Yin L, Yu X (2018) Arsenic-induced apoptosis in the p53-proficient and p53-deficient cells through differential modulation of NFkB pathway. Food Chem Toxicol 118:849–860. https://doi.org/10.1016/j.fct.2018.06.053
Zhang B, Xue Y, Zhao J, Jiang H, Zhu J, Yin H, Qiu Y, Hu A, Xu L, Song Y, Wang X (2022) Shionone attenuates sepsis-induced acute kidney injury by regulating macrophage polarization via the ECM1/STAT5 pathway. Front Med 8:796743. https://doi.org/10.3389/fmed.2021.796743
Zhou WB, Zeng GZ, Xu HM, He WJ, Zhang YM, Tan NH (2014) Astershionones A-F, six new anti-HBV shionane-type triterpenes from Aster tataricus. Fitoterapia 93:98–104. https://doi.org/10.1016/j.fitote.2013.12.021
Zhu L, Shen H, Gu PQ, Liu YJ, Zhang L, Cheng JF (2020) Baicalin alleviates TNBS-induced colitis by inhibiting PI3K/AKT pathway activation. Exp Ther Med 20:581–590. https://doi.org/10.3892/etm.2020.8718
Funding
No funding was received.
Author information
Authors and Affiliations
Contributions
PW: conceptualization, formal analysis, project administration, writing, review and editing of the original draft. ZC: supervision, visualization, and writing, review, and editing. YW and XL: investigation, methodology, software, and validation. All authors have read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics Approval
Not applicable.
Competing Interests
The authors declare that they have no competing interests.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Wei, P., Wang, Y., Li, X. et al. Shionone Relieves Ulcerative Colitis by Regulating the p38 MAPK/NF-κB Pathway. Rev. Bras. Farmacogn. (2024). https://doi.org/10.1007/s43450-024-00552-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s43450-024-00552-5