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Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Research Article

Sericic Acid Ameliorates DSS-induced Ulcerative Colitis in Mice by Modulating the NF-κB and Nrf2 Pathways

Author(s): Lifei-Luo, Jingze Zhang, Xinyu Li, Yanru Zhu, Yansheng Wang and Dailin Liu*

Volume 16, Issue 7, 2023

Published on: 27 December, 2022

Article ID: e280922209224 Pages: 12

DOI: 10.2174/1874467215666220928100319

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Abstract

Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease. In previous studies, we found extracts from the roots of Rosa odorata Sweet var. gigantea (Coll.et Hemsl.) Rehd. et Wils have a therapeutic effect on UC. Furthermore, sericic acid (SA) is a pentacyclic triterpenoid isolated from this plant that is being used for the first time. The purpose of this study was to investigate whether SA has anti-inflammatory and therapeutic effects on UC and its underlying mechanisms.

Methods: In this study, we used a dextran sulfate-induced UC mouse model and lipopolysaccharide (LPS)-induced inflammatory cell model along with an enzyme-linked immunosorbent assay (ELISA) to quantify the abundance of inflammatory factors and oxidative stress factors in tissues and cells. HE staining was used to analyze the therapeutic effect of the drugs on the UC mouse model. The expression levels of oxidative stress-related proteins were detected using immunoblotting and immunohistochemistry. The anti-inflammatory targets of SA were screened using protein chip arrays and verified by immunoblotting.

Results: We found that SA had anti-inflammatory and antioxidant effects in animal and cellular inflammation models. SA inhibited the levels of NO, TNF-α, IL-6, IL-1β, and MDA in tissues and cells and upregulated the expression level of SOD. Animal experiments showed that SA alleviated the shortening of colon length and colon pathological damage caused by DSS. The antiinflammatory targets of SA were screened using protein chip arrays, and SA was found to inhibit proteins related to the NF-κB signaling pathway. Finally, immunoblotting and immunohistochemistry showed that SA downregulated the expression of p-IKKα/β and its downstream protein p-NF-κB, while promoting the expression of Nrf2 and its downstream protein HO-1.

Conclusion: The above results indicated that SA alleviated DSS-induced colitis by inhibiting NF-κB signaling pathway and activating Nrf2 pathway.

Keywords: Rosa odorata , Sericic acid, Ulcerative colitis, Inflammatory, cytokines, Nrf2, NF-κB

Graphical Abstract

[1]
Magro, F.; Alves, C.; Santiago, M.; Ministro, P.; Lago, P.; Correia, L.; Gonçalves, R.; Carvalho, D.; Portela, F.; Dias, C.C.; Dignass, A.; Danese, S.; Peyrin-Biroulet, L.; Estevinho, M.M.; Moreira, P. Composite outcomes in observational studies of ulcerative colitis: A systematic review and meta-analysis. United European Gastroenterol. J., 2022, 10(1), 54-72.
[http://dx.doi.org/10.1002/ueg2.12183] [PMID: 34907660]
[2]
Ortenzi, M.; Balla, A.; Lezoche, G.; Colozzi, S.; Vergari, R.; Corallino, D.; Palmieri, L.; Meoli, F.; Paganini, A.M.; Guerrieri, M. Complications after bowel resection for inflammatory bowel disease associated cancer: A systematic literature review. Minerva Surg., 2022, 77(3), 272-280.
[http://dx.doi.org/10.23736/S2724-5691.22.09369-8] [PMID: 35175015]
[3]
Safwat El-Deeb, O.; El-Esawy, R.O.; Al-Shenawy, H.A.; Ghanem, H.B. Modulating gut dysbiosis and mitochondrial dysfunction in oxazolone-induced ulcerative colitis: The restorative effects of β-glucan and/or celastrol. Redox Rep., 2022, 27(1), 60-69.
[http://dx.doi.org/10.1080/13510002.2022.2046425] [PMID: 35246012]
[4]
Rao, Q.; Ma, G.; Wu, H.; Li, M.; Xu, W.; Wang, G.; Wang, D.; Zhang, C.; Ma, Z.; Zhang, Z. Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models. Drug Deliv., 2022, 29(1), 679-691.
[http://dx.doi.org/10.1080/10717544.2022.2044935] [PMID: 35225120]
[5]
Farsi, F.; Ebrahimi-Daryani, N.; Golab, F.; Akbari, A.; Janani, L.; Karimi, M.Y.; Irandoost, P.; Alamdari, N.M.; Agah, S.; Vafa, M. RETRACTED ARTICLE: A randomized controlled trial on the coloprotective effect of coenzyme Q10 on immune-inflammatory cytokines, oxidative status, antimicrobial peptides, and microRNA-146a expression in patients with mild-to-moderate ulcerative colitis. Eur. J. Nutr., 2021, 60(6), 3397-3410.
[http://dx.doi.org/10.1007/s00394-021-02514-2] [PMID: 33620550]
[6]
Salah, N.; Dubuquoy, L.; Carpentier, R.; Betbeder, D. Starch nanoparticles improve curcumin-induced production of anti-inflammatory cytokines in intestinal epithelial cells. Int. J. Pharm. X, 2022, 4, 100114.
[http://dx.doi.org/10.1016/j.ijpx.2022.100114] [PMID: 35295898]
[7]
Luo, H.; Cao, G.; Luo, C.; Tan, D.; Vong, C.T.; Xu, Y.; Wang, S.; Lu, H.; Wang, Y.; Jing, W. Emerging pharmacotherapy for inflammatory bowel diseases. Pharmacol. Res., 2022, 178, 106146.
[http://dx.doi.org/10.1016/j.phrs.2022.106146] [PMID: 35227890]
[8]
Gupta, M.; Mishra, V.; Gulati, M.; Kapoor, B.; Kaur, A.; Gupta, R.; Tambuwala, M.M. Natural compounds as safe therapeutic options for ulcerative colitis. Inflammopharmacology, 2022, 30(2), 397-434.
[http://dx.doi.org/10.1007/s10787-022-00931-1] [PMID: 35212849]
[9]
Wang, Z.; Li, C.; He, X.; Xu, K.; Xue, Z.; Wang, T.; Xu, Z.; Liu, X. Platycodon grandiflorum root fermentation broth reduces inflammation in a mouse IBD model through the AMPK/NF-κB/NLRP3 pathway. Food Funct., 2022, 13(7), 3946-3956.
[http://dx.doi.org/10.1039/D1FO03969E] [PMID: 35293398]
[10]
Fan, M.; Wu, X.; Li, X.; Piao, X.; Jiang, J.; Lian, M. Co-cultured adventitious roots of Echinacea pallida and Echinacea purpurea inhibit lipopolysaccharide-induced inflammation via MAPK pathway in mouse peritoneal macrophages. Chin. Herb. Med., 2021, 13(2), 228-234.
[http://dx.doi.org/10.1016/j.chmed.2021.01.001]
[11]
Zhou, Y.; Dou, F.; Song, H.; Liu, T. Anti-ulcerative effects of wogonin on ulcerative colitis induced by dextran sulfate sodium via Nrf2/TLR4/NF-κB signaling pathway in BALB/c mice. Environ. Toxicol., 2022, 37(4), 954-963.
[http://dx.doi.org/10.1002/tox.23457] [PMID: 35044701]
[12]
Guo, W.; Zhang, Q.; Du, Y.; Guo, J.; Zhao, T.; Bai, L.; An, X. Immunomodulatory activity of polysaccharides from Brassica rapa by activating Akt/NF-κB signaling. Chin. Herb. Med., 2022, 14(1), 90-96.
[http://dx.doi.org/10.1016/j.chmed.2021.10.003]
[13]
Gazouli, M.; Dovrolis, N.; Bourdakou, M.M.; Gizis, M.; Kokkotis, G.; Kolios, G.; Michalopoulos, G.; Michopoulos, S.; Papaconstantinou, I.; Tzouvala, M.; Viazis, N.; Xourafas, V.; Zacharopoulou, E.; Zampeli, E.; Mantzaris, G.; Papatheodoridis, G.; Bamias, G. Response to anti-α4β7 blockade in patients with ulcerative colitis is associated with distinct mucosal gene expression profiles at baseline. Inflamm. Bowel Dis., 2022, 28(1), 87-95.
[http://dx.doi.org/10.1093/ibd/izab117] [PMID: 34042157]
[14]
Baud, V.; Jacque, E. The alternative NF-kB activation pathway and cancer: Friend or foe? Med. Sci., 2008, 24(12), 1083-1088.
[http://dx.doi.org/10.1051/medsci/200824121083] [PMID: 19116119]
[15]
Pisani, L.F.; Tontini, G.; Vecchi, M.; Croci, G.A.; Pastorelli, L. NF-kB pathway is involved in microscopic colitis pathogenesis. J. Int. Med. Res., 2022, 50(3)
[http://dx.doi.org/10.1177/03000605221080104] [PMID: 35301900]
[16]
Li, X.; Liu, R.; Zhao, Y.; Gao, N.; Jin, X.; Gao, X.; Li, T.; Liu, D. The extract from the roots of Rose odorata sweet var. gigantean (Coll. et Hemsl.) Rehd. et Wils attenuates DSS-induced ulcerative colitis by regulating the Nrf2/NF-κB signaling pathways. RSC Advances, 2020, 10(16), 9450-9461.
[http://dx.doi.org/10.1039/C9RA10747A] [PMID: 35692958]
[17]
Cheng, B.C.Y.; Fu, X.Q.; Guo, H.; Li, T.; Wu, Z.Z.; Chan, K.; Yu, Z.L. The genus Rosa and arthritis: Overview on pharmacological perspectives. Pharmacol. Res., 2016, 114, 219-234.
[http://dx.doi.org/10.1016/j.phrs.2016.10.029] [PMID: 27816506]
[18]
Wu, C.; Chen, R.L.; Wang, Y.; Wu, W.Y.; Li, G. Acacetin alleviates myocardial ischaemia/reperfusion injury by inhibiting oxidative stress and apoptosis via the Nrf-2/HO-1 pathway. Pharm. Biol., 2022, 60(1), 553-561.
[http://dx.doi.org/10.1080/13880209.2022.2041675] [PMID: 35244510]
[19]
Nattagh-Eshtivani, E.; Barghchi, H.; Pahlavani, N.; Barati, M.; Amiri, Y.; Fadel, A.; Khosravi, M.; Talebi, S.; Arzhang, P.; Ziaei, R.; Ghavami, A. Biological and pharmacological effects and nutritional impact of phytosterols: A comprehensive review. Phytother. Res., 2022, 36(1), 299-322.
[http://dx.doi.org/10.1002/ptr.7312] [PMID: 34729825]
[20]
Wang, H.; Yu, W.; Zhang, D.; Zhao, Y.; Chen, C.; Zhu, H.; Cai, E.; Yan, Z. Cytotoxic and anti-tumor effects of 3,4- seco -lupane triterpenoids from the leaves of Eleutherococcus sessiliflorus against hepatocellular carcinoma. Nat. Prod. Res., 2022, 36(4), 1062-1066.
[http://dx.doi.org/10.1080/14786419.2020.1844698] [PMID: 33183092]
[21]
Kou, R.W.; Xia, B.; Wang, Z.J.; Li, J.N.; Yang, J.R.; Gao, Y.Q.; Yin, X.; Gao, J.M. Triterpenoids and meroterpenoids from the edible Ganoderma resinaceum and their potential anti-inflammatory, antioxidant and anti-apoptosis activities. Bioorg. Chem., 2022, 121, 105689.
[http://dx.doi.org/10.1016/j.bioorg.2022.105689] [PMID: 35217377]
[22]
Hess, S.C.; Brum, R.L.; Honda, N.K.; Cruz, A.B.; Moretto, E.; Cruz, R.B.; Messana, I.; Ferrari, F.; Filho, V.C.; Yunes, R.A. Antibacterial activity and phytochemical analysis of Vochysia divergens (Vochysiaceae). J. Ethnopharmacol., 1995, 47(2), 97-100.
[http://dx.doi.org/10.1016/0378-8741(95)01260-K] [PMID: 7500642]
[23]
Wang, O.; Liu, S.; Zou, J.; Lu, L.; Chen, L.; Qiu, S.; Li, H.; Lu, X. Anticancer activity of 2α 3α 19β 23β-tetrahydroxyurs-12-en-28-oic acid (THA), a novel triterpenoid isolated from Sinojackia sarcocarpa. PLoS One, 2011, 6(6), e21130.
[http://dx.doi.org/10.1371/journal.pone.0021130] [PMID: 21695177]
[24]
Louis, E.; Paridaens, K.; Al Awadhi, S.; Begun, J.; Cheon, J.H.; Dignass, A.U.; Magro, F.; Márquez, J.R.; Moschen, A.R.; Narula, N.; Rydzewska, G.; Freddi, M.J.; Travis, S.P.L. Modelling the benefits of an optimised treatment strategy for 5-ASA in mild-to-moderate ulcerative colitis. BMJ Open Gastroenterol., 2022, 9(1), e000853.
[http://dx.doi.org/10.1136/bmjgast-2021-000853] [PMID: 35165124]
[25]
Erben, U.; Loddenkemper, C.; Doerfel, K.; Spieckermann, S.; Haller, D.; Heimesaat, M.M.; Zeitz, M.; Siegmund, B.; Kühl, A.A. A guide to histomorphological evaluation of intestinal inflammation in mouse models. Int. J. Clin. Exp. Pathol., 2014, 7(8), 4557-4576.
[PMID: 25197329]
[26]
Li, B.L.; Yuan, J.; Wu, J.W. A review on the phytochemical and pharmacological properties of Rosa laevigata: A medicinal and edible plant. Chem. Pharm. Bull., 2021, 69(5), 421-431.
[http://dx.doi.org/10.1248/cpb.c20-00743] [PMID: 33952852]
[27]
Santos Silva, J.; França Ferreira, É.L.; Maciel Lima, A.; de Farias, R.R.S.; Quirino Araújo, B.; Quilles, J.C., Junior; Lima Santos, R.R.; de Amorim Carvalho, F.A.; Rai, M.; Vieira Júnior, G.M.; Chaves, M.H. Four new cycloartane-type triterpenoids from the leaves of Combretum mellifluum Eichler: Assessment of their antioxidant and antileishmanial activities. J. Toxicol. Environ. Health A, 2022, 85(9), 364-375.
[http://dx.doi.org/10.1080/15287394.2021.2015030] [PMID: 34933666]
[28]
Tatiya-aphiradee, N.; Chatuphonprasert, W.; Jarukamjorn, K. Immune response and inflammatory pathway of ulcerative colitis. J. Basic Clin. Physiol. Pharmacol., 2018, 30(1), 1-10.
[http://dx.doi.org/10.1515/jbcpp-2018-0036] [PMID: 30063466]
[29]
Fu, Y.P.; Yuan, H.; Xu, Y.; Liu, R.M.; Luo, Y.; Xiao, J.H. Protective effects of Ligularia fischeri root extracts against ulcerative colitis in mice through activation of Bcl-2/Bax signalings. Phytomedicine, 2022, 99, 154006.
[http://dx.doi.org/10.1016/j.phymed.2022.154006] [PMID: 35299029]
[30]
Piotrowska, M.; Swierczynski, M.; Fichna, J.; Piechota-Polanczyk, A. The Nrf2 in the pathophysiology of the intestine: Molecular mechanisms and therapeutic implications for inflammatory bowel diseases. Pharmacol. Res., 2021, 163, 105243.
[http://dx.doi.org/10.1016/j.phrs.2020.105243] [PMID: 33080322]
[31]
Khor, T.O.; Huang, M.T.; Kwon, K.H.; Chan, J.Y.; Reddy, B.S.; Kong, A.N. Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis. Cancer Res., 2006, 66(24), 11580-11584.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3562] [PMID: 17178849]
[32]
Alsharif, I.A.; Fayed, H.M.; Abdel-Rahman, R.F.; Abd-Elsalam, R.M.; Ogaly, H.A. Miconazole mitigates acetic acid-induced experimental colitis in rats: Insight into inflammation, oxidative stress and Keap1/Nrf-2 signaling crosstalk. Biology, 2022, 11(2), 303.
[http://dx.doi.org/10.3390/biology11020303] [PMID: 35205169]
[33]
Liu, C.; Hua, H.; Zhu, H.; Cheng, Y.; Guo, Y.; Yao, W.; Qian, H. Aloe polysaccharides ameliorate acute colitis in mice via Nrf2/HO-1 signaling pathway and short-chain fatty acids metabolism. Int. J. Biol. Macromol., 2021, 185, 804-812.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.07.007] [PMID: 34229016]
[34]
Makled, M.N.; Serrya, M.S.; El-Sheakh, A.R. Fingolimod ameliorates acetic acid-induced ulcerative colitis: An insight into its modulatory impact on pro/anti-inflammatory cytokines and AKT/mTOR signalling. Basic Clin. Pharmacol. Toxicol., 2022, 130(5), 569-580.
[http://dx.doi.org/10.1111/bcpt.13720] [PMID: 35274449]
[35]
Kopacz, A.; Kloska, D.; Forman, H.J.; Jozkowicz, A.; Grochot-Przeczek, A. Beyond repression of Nrf2: An update on Keap1. Free Radic. Biol. Med., 2020, 157, 63-74.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.03.023] [PMID: 32234331]
[36]
Baird, L.; Yamamoto, M. The molecular mechanisms regulating the KEAP1-NRF2 pathway. Mol. Cell. Biol., 2020, 40(13), e00099-e20.
[http://dx.doi.org/10.1128/MCB.00099-20] [PMID: 32284348]
[37]
Marônek, M.; Marafini, I.; Gardlík, R.; Link, R.; Troncone, E.; Monteleone, G. Metalloproteinases in inflammatory bowel diseases. J. Inflamm. Res., 2021, 14, 1029-1041.
[http://dx.doi.org/10.2147/JIR.S288280] [PMID: 33790618]

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