Li-Hong Tang Alleviates Dextran Sodium Sulfate-induced Colitis by Regulating NRF2/HO-1 Signaling Pathway and Gut Microbiota

Overview

Journal Front Pharmacol

Date 2024 Jun 14

PMID 38873425

Authors

Hong Gu

Yuwen Tian

Jingjing Xia

Xiaoyue Deng

Jian Chen

Tunyu Jian

Jiong Ma

Affiliations

Soon will be listed here.

Abstract

Introduction: Ulcerative colitis (UC) is marked by recurring inflammation. Existing treatments are ineffective and may have toxic side effects. Thus, new therapeutic agents are urgently needed. We studied the botanical formula "Li-Hong Tang (LHT)", which contains two main ingredients, R. Br and (Hook. f. et Thoms.) H. Ohba. In this study, we aimed to identify the effects of LHT on UC and explore its potential mechanism.

Methods: LHT was analyzed using a mass spectrometer (MS). DSS at a dose of 2.5% was utilized to develop UC in mice. The administered groups received low, medium, and high dosages (0.32 g/kg, 0.64 g/kg, and 1.28 g/kg) of LHT and the positive medication, sulfasalazine (0.2 g/kg), respectively. Body weight, disease activity index (DAI) score, colon length, spleen index, serum myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD) and inflammatory factor concentrations were monitored. The expression of NRF2 and HO-1 in colonic tissues was evaluated by immunohistochemistry. 16S rDNA sequencing was employed to investigate alterations in the gut microbiota of the mice, aiming to elucidate the extent of LHT's impact.

Results: LHT may ameliorate DSS-induced colitis in mice by lowering inflammation, reducing oxidative stress, restoring the intestinal barrier, and influencing the NRF2/HO-1 pathway. Moreover, LHT treatment exhibited a regulatory effect on the gut microbiota, characterized by elevated levels of Patescibacteria, Verrucomicrobiota, , , and levels while decreasing and r levels. Further study indicated that MPO, NO, and inflammatory factors were positively correlated with , , , , and negatively with , , and Patescibacteria. Furthermore, colony network analysis revealed that was negatively associated with and , whereas was positively related to .

Conclusion: LHT protects against DSS-induced mice by inhibiting the inflammatory response, oxidative stress, and mucosal injury. The protective role may involve regulating the NRF2/HO-1 signaling pathway and gut microbiota.

Citing Articles

Integrated Macrogenomics and Metabolomics Analysis of the Effect of Sea Cucumber Ovum Hydrolysates on Dextran Sodium Sulfate-Induced Colitis.

Gong S, Sun L, Sun Y, Ju W, Wang G, Zhang J Mar Drugs. 2025; 23(2).

PMID: 39997197 PMC: 11857712. DOI: 10.3390/md23020073.

References

Bai X, Deng X, Wu G, Li W, Jin S . Rhodiola and salidroside in the treatment of metabolic disorders. Mini Rev Med Chem. 2019; 19(19):1611-1626. DOI: 10.2174/1389557519666190903115424. View

Peng S, Shen L, Yu X, Zhang L, Xu K, Xia Y . The role of Nrf2 in the pathogenesis and treatment of ulcerative colitis. Front Immunol. 2023; 14:1200111. PMC: 10285877. DOI: 10.3389/fimmu.2023.1200111. View

Gu Z, Zhu Y, Mei F, Dong X, Xia G, Shen X . Tilapia head glycolipids protect mice against dextran sulfate sodium-induced colitis by ameliorating the gut barrier and suppressing NF-kappa B signaling pathway. Int Immunopharmacol. 2021; 96:107802. DOI: 10.1016/j.intimp.2021.107802. View

Wang C, Li W, Wang H, Ma Y, Zhao X, Yang H . VSL#3 can prevent ulcerative colitis-associated carcinogenesis in mice. World J Gastroenterol. 2018; 24(37):4254-4262. PMC: 6175759. DOI: 10.3748/wjg.v24.i37.4254. View

Li W, Liu J, Wang Z, Wang K, Huang C, He W . Sinapic Acid Attenuates Chronic DSS-Induced Intestinal Fibrosis in C57BL/6J Mice by Modulating NLRP3 Inflammasome Activation and the Autophagy Pathway. ACS Omega. 2024; 9(1):1230-1241. PMC: 10785090. DOI: 10.1021/acsomega.3c07474. View

Brown D, Barton G, Pan Z, Buck M, Wigneshweraraj S . Nitrogen stress response and stringent response are coupled in Escherichia coli. Nat Commun. 2014; 5:4115. PMC: 4066584. DOI: 10.1038/ncomms5115. View

Kim M, Jeon J . Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases. Int J Mol Sci. 2022; 23(5). PMC: 8910922. DOI: 10.3390/ijms23052846. View

Nadel J, Jabbour A, Stocker R . Arterial myeloperoxidase in the detection and treatment of vulnerable atherosclerotic plaque: a new dawn for an old light. Cardiovasc Res. 2022; 119(1):112-120. DOI: 10.1093/cvr/cvac081. View

Girdhar K, Dogru Y, Huang Q, Yang Y, Tolstikov V, Raisingani A . Dynamics of the gut microbiome, IgA response, and plasma metabolome in the development of pediatric celiac disease. Microbiome. 2023; 11(1):9. PMC: 9840338. DOI: 10.1186/s40168-022-01429-2. View

10.

Li Y, Zou M, Han Q, Deng L, Weinshilboum R . Therapeutic potential of triterpenoid saponin anemoside B4 from Pulsatilla chinensis. Pharmacol Res. 2020; 160:105079. DOI: 10.1016/j.phrs.2020.105079. View

11.

Li L, Xu M, Shen B, Li M, Gao Q, Wei S . Moderate exercise prevents neurodegeneration in D-galactose-induced aging mice. Neural Regen Res. 2016; 11(5):807-15. PMC: 4904473. DOI: 10.4103/1673-5374.182709. View

12.

Yin H, Zhong Y, Wang H, Hu J, Xia S, Xiao Y . Short-term exposure to high relative humidity increases blood urea and influences colonic urea-nitrogen metabolism by altering the gut microbiota. J Adv Res. 2022; 35:153-168. PMC: 8721250. DOI: 10.1016/j.jare.2021.03.004. View

13.

Lam Y, Ha C, Campbell C, Mitchell A, Dinudom A, Oscarsson J . Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice. PLoS One. 2012; 7(3):e34233. PMC: 3311621. DOI: 10.1371/journal.pone.0034233. View

14.

Ni J, Shen T, Chen E, Bittinger K, Bailey A, Roggiani M . A role for bacterial urease in gut dysbiosis and Crohn's disease. Sci Transl Med. 2017; 9(416). PMC: 5808452. DOI: 10.1126/scitranslmed.aah6888. View

15.

Hwang Y, Nam S, Chun W, Kim S, Park S, Kang C . Anti-inflammatory effects of apocynin on dextran sulfate sodium-induced mouse colitis model. PLoS One. 2019; 14(5):e0217642. PMC: 6541291. DOI: 10.1371/journal.pone.0217642. View

16.

Zhou Y, Wang D, Yan W . Treatment Effects of Natural Products on Inflammatory Bowel Disease In Vivo and Their Mechanisms: Based on Animal Experiments. Nutrients. 2023; 15(4). PMC: 9967064. DOI: 10.3390/nu15041031. View

17.

Huang C, Luo X, Li L, Xue N, Dang Y, Zhang H . Polysaccharide Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice. Evid Based Complement Alternat Med. 2022; 2022:1345852. PMC: 9012628. DOI: 10.1155/2022/1345852. View

18.

Gomez J, Dang H, Martin J, Doerschuk C . Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice. J Immunol. 2016; 197(7):2864-79. PMC: 5026972. DOI: 10.4049/jimmunol.1600043. View

19.

Xu M, Jiang P, Sun H, Yuan X, Gao S, Guo J . Dimethyl itaconate protects against lipopolysaccharide-induced endometritis by inhibition of TLR4/NF-κB and activation of Nrf2/HO-1 signaling pathway in mice. Iran J Basic Med Sci. 2020; 23(9):1239-1244. PMC: 7491490. DOI: 10.22038/ijbms.2020.44151.10346. View

20.

Zhang X, Yuan Z, Qu C, Yu X, Huang T, Chen P . Palmatine ameliorated murine colitis by suppressing tryptophan metabolism and regulating gut microbiota. Pharmacol Res. 2018; 137:34-46. DOI: 10.1016/j.phrs.2018.09.010. View