Skip to main content

Advertisement

SpringerLink
Log in

Lizhong Decoction Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics.

Methods

Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software.

Results

The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels.

Conclusions

The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Prince AC, Myers CE, Joyce T, Irving P, Lomer M, Whelan K. Fermentable carbohydrate restriction (low FODMAP diet) in clinical practice improves functional gastrointestinal symptoms in patients with inflammatory bowel disease. Inflamm Bowel Dis 2016;22:1129–1136.

    Article  PubMed  Google Scholar 

  2. Walker AW, Sanderson JD, Churcher C, Parkes GC, Hudspith BN, Netal R. High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol 2011;1:7–10.

    Article  Google Scholar 

  3. Cammarota G, Ianiro G, Cianci R, Bibbo S, Gasbarrini A, Curro D. The involvement of gut microbiota in inflammatory bowel disease pathogenesis: potential for therapy. Pharmacol Ther 2015;149:191–212.

    Article  CAS  PubMed  Google Scholar 

  4. Chen Q, Gou S, Huang Y, Zhou X, Li Q, Han MK, et al. Facile fabrication of bowl-shaped microparticles for oral curcumin delivery to ulcerative colitis tissue. Colloids Surf B 2018;169:92–98.

    Article  CAS  Google Scholar 

  5. Xiao B, Chen Q, Zhang Z, Wang L, Kang Y, Denning T, et al. TNF-α gene silencing mediated by orally targeted nanoparticles combined with interleukin-22 for synergistic combination therapy of ulcerative colitis. J Control Release 2018;287:235–246.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ma QH, Ren MY, Luo JB. Sanwu Huangqin Decoction regulates inflammation and immune dysfunction induced by influenza virus by regulating the NF-κ B signaling pathway in H1N1-infected mice. J Ethnopharmacol 2020;264:112800.

    Article  PubMed  Google Scholar 

  7. Altomare R, Damiano G, Abruzzo A, Palumbo VD, Tomasello G, Buscemi S, et al. Enteral nutrition support to treat malnutrition in inflammatory bowel disease. Nutrients 2015;7:2125–2133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jayawardena D, Anbazhagan AN, Guzman G, Dudeja PK, Onyuksel H. Vasoactive intestinal peptide nanomedicine for the management of inflammatory bowel disease. Mol Pharm 2017;14:3698–3708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang HB, Lin Y. Traditional Chinese medicine diagnosis and treatment of ulcerative colitis. Chin J Clin (Chin) 2018;5:515–517.

    Google Scholar 

  10. Fei ZY. Clinical research and syndrome suitable for regulating Lizhong Decoction [dissertation]. Beijing: Beijing University of Traditional Chinese Medicine; 2011.

    Google Scholar 

  11. Duan YQ, Chen WD, Cheng YX, Du J, Kong ZH, Zhu LM, et al. Comparative study of Sijunzi Decoction and Lizhong Decoction on gastrointestinal transport function, gastrointestinal hormone substance P and cholecystokinin in diarrhea IBS rats. Chin Tradit Pat Med (Chin) 2015;37:405–408.

    Google Scholar 

  12. Kim JH, Yi YS, Kim MY, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Gins Res 2017;41:435–443.

    Article  Google Scholar 

  13. Li F, Nitteranon V, Tang XZ. In vitro antioxidant and anti-inflammatory activities of 1-dehydro-[6]-gingerdione, 6-shogaol, 6-dehydroshogaol and hexahydrocurcumin. Food Chem 2012;135:332–337.

    Article  CAS  PubMed  Google Scholar 

  14. Tao JH, Duan JA, Jiang S, Qian YY, Wei XY. Polysaccharides from Chrysanthemum morifolium Ramat ameliorate colitis rats via regulation of the metabolic profiling and NF-κ B and IL-6 signaling pathways. Front Pharmacol 2018;9:746.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Su S, Duan J, Chen T, Huang X, Shang E, Li Y. Corrigendum: frankincense and myrrh suppress inflammation via regulation of the metabolic profiling and the MAPK signaling pathway. Sci Rep 2015;5:15597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Phua LC, Koh PK, Cheah PY. Global gas chromatography/time-of-flight mass spectrometry (GC/TOFMS)-based metabonomic profiling of lyophilized human feces. J Chromatogr B 2013;937C:103–113.

    Article  Google Scholar 

  17. Shen Y, Zou J, Zhang Z, Chen M, Duan JA. Protective effects of Lizhong Decoction on ulcerative colitis mice by suppressing inflammation and ameliorating gut barrier. J Ethnopharmacol 2020;259:112919–112925.

    Article  CAS  PubMed  Google Scholar 

  18. Zhu YS, Li XQ, Chen JQ, Chen TJ, Shi ZM, Lei MN, et al. The pentacyclic triterpene Lupeol switches M1 macrophages to M2 and ameliorates experimental inflammatory bowel disease. Int Immunopharmacol 2016;30:74–84.

    Article  CAS  PubMed  Google Scholar 

  19. Li X, Xu Y, Zhang C, Deng L, Cheng M, Yu Z, et al. Protective effect of Calculus bovis Sativus on dextran sulphate sodiuminduced ulcerative colitis in mice. Evid Based Complement Altern Med 2015;2015:469506.

    Article  Google Scholar 

  20. Pan T, Guo HY, Zhang H, Liu AP, Wang XX, Ren FZ. Oral administration of Lactobacillus paracasei alleviates clinical symptoms of colitis induced by dextran sulphate sodium salt in BALB/c mice. Benef Microbesn 2014;5:315–322.

    Article  CAS  Google Scholar 

  21. Zhang X, Choi FF, Zhou Y, Leunq FP, Tan S, Lin S, et al. Metabolite profiling of plasma and urine from rats with TNBS-induced acute colitis using UPLC-ESI-QTOF-MS-based metabonomics-a pilot study. FEBS J 2012;279:2322–2338.

    Article  CAS  PubMed  Google Scholar 

  22. Salim SY, Soderholm JD. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis 2011;17:362–381.

    Article  PubMed  Google Scholar 

  23. Chanukuppa V, Taware R, Chatterjee T, Sharma S, More T, Taunk K, et al. Current understanding of the potential of proteomics and metabolomics approaches in cancer chemoresistance: a focus on multiple myeloma. Curr Med Chem 2019;18:2584–2598.

    Article  Google Scholar 

  24. Blackwood B, Alderdice E, Burns K, Cardwell C, Lavery G, O’halloran P. Use of weaning protocols for reducing duration of mechanical ventilation in critically ill adult patients: cochrane systematic review and meta-analysis. BMJ 2011;324:c7237.

    Article  Google Scholar 

  25. Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 2013;62:531–539.

    Article  CAS  PubMed  Google Scholar 

  26. Pols TW, Noriega LG, Nomura M, Auwerx J, Schoonjans K. The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation. J Hepatol 2011;54:1263–1272.

    Article  CAS  PubMed  Google Scholar 

  27. Del Angel-Meza AR, Dávalos-Marín AJ, Ontiveros-Martinez LL, Ortiz GG, Beas-Zarate C, Chaparro-Huerta V, et al. Protective effects of tryptophan on neuroinflammation in rats after administering lipopolysaccharide. Biomed Pharmacother 2011;65:215–219.

    Article  CAS  PubMed  Google Scholar 

  28. Verbeke L, Farre R, Verbinnen B, Covens K, Vanuytsel T, Verhagen J, et al. The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats. Am J Pathol 2015;185:409–419.

    Article  CAS  PubMed  Google Scholar 

  29. Kim CJ, Kovacs-Nolan JA, Yang C, Archbold T, Fan MZ, Mine Y. l-Tryptophan exhibits therapeutic function in a porcine model of dextran sodium sulfate (DSS)-induced colitis. J Nutr Biochem 2010;21:468–475.

    Article  CAS  PubMed  Google Scholar 

  30. Shiomi Y, Nishiumi S, Ooi M, Hatano N, Shinohara M, Yoshie T, et al. GCMS-based metabolomics study in mice with colitis induced by dextran sulfate sodium. Inflamm Bowel Dis 2011;17:2261–2274.

    Article  PubMed  Google Scholar 

  31. Castejón ML, Rosillo MN, Villegas I. Quercus ilex Extract ameliorates acute TNBS-induced colitis in rats. Planta Med 2019;85:670–677.

    Article  PubMed  Google Scholar 

  32. Li Z, Li J, Zhang S, Chen G, Chi S, Li X, et al. Metabolomics analysis of gut barrier dysfunction in a trauma-hemorrhagic shock rat model. Biosci Rep 2019;39:BSR20181215.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Tu L, Pan CS, Wei XH, Yan L, Liu YY, Fan JY, et al. Astragaloside IV protects heart from ischemia and reperfusion injury via energy regulation mechanisms. Microcirculation 2013;20:736–747.

    CAS  PubMed  Google Scholar 

  34. Kim SM, Neuendorff N, Earnest DJ. Role of proinflammatory cytokines in feedback modulation of circadian clock gene rhythms by saturated fatty acids. Sci Rep 2019;9:8909–8918.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gault CR, Obeid LM, Hannun YA. An overview of sphingolipid metabolism: from synthesis to breakdown. Adv Exp Med Biol 2010;688:1–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fabrias G, Munoz-Olava J, Cinqolani F, Siqnorelli P, Casas J, Gaqliostrov V, et al. Dihydroceramide desaturase and dihydrosphingolipids: debutant players in the sphingolipid arena. Proq Lipid Res 2012;51:82–94.

    Article  CAS  Google Scholar 

  37. Maceyka M, Spiegel S. Sphingolipid metabolites in inflammatory disease. Nature 2014;510:58–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Suh JH, Deqaqne E, Gleqhorn EE, Setty M, Rodriquez A, Park KT, et al. Sphingosine-1-phosphate signaling and metabolism gene signature in pediatric inflammatory bowel disease: a matched-case control pilot study. Inflamm Bowel Dis 2018;24:1321–1334.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Toyoizumi T, Ohba S, Takano-Ishikawa Y. Placental tissue of greenhouse muskmelon (Cucumis melo L.) contains more gamma-aminobutyric acid with antioxidant capacity than the fleshed pulp. Biosci Biotech Bioch 2020;84:1211–1220.

    Article  CAS  Google Scholar 

  40. Auteri M, Zizzo MG, Serio R. GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation. Pharmacol Res 2015;93:13–21.

    Article  Google Scholar 

  41. Ma X, Sun X, Chen D, Wei C, Yu X, Liu C, et al. Activation of GABA-A receptors in colon epithelium exacerbates acute colitis. Front Immunl 2018;9:987.

    Article  Google Scholar 

  42. Prud’homme GJ, Glinka Y, Udovyk O, Hasilo C, Paraskevas S, Wang Q. GABA protects pancreatic beta cells against apoptosis by increasing SIRT1 expression and activity. Biochem Biophys Res Commun 2014;452:649–654.

    Article  PubMed  Google Scholar 

  43. Viana ML, Santos RGC, Generoso SV, Nicoli JR, Martins FS, Noqueira-Machado JA, et al. The role of L-arginine-nitric oxide pathway in bacterial translocation. Amino Acids 2013;45:1089–1096.

    Article  CAS  PubMed  Google Scholar 

  44. Sina C, Kemper C, Derer S. The intestinal complement system in inflammatory bowel disease: shaping intestinal barrier function. Semin Immunol 2018;37:66–73.

    Article  CAS  PubMed  Google Scholar 

  45. Zhu H, Pi D, Leng W, Wang X, Hu CA, Huo Y, et al. It happens that nutrient such as amino acids and fatty acids are thought to be regulators for the repair of intestinal barriers. Innate Immun 2017;23:546–556.

    Article  CAS  PubMed  Google Scholar 

  46. Werz O, Gerstmeier J, Garscha U. Novel leukotriene biosynthesis inhibitors (2012–2016) as anti-inflammatory agents. Expert Opin Ther Pat 2017;27:607–620.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pharmacy, Nantong University, Nantong, Jiangsu Province, 226001, China

    Ling Wang, Jin-hua Tao & Yi-fan Chen

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

    Yu-meng Shen & Shu Jiang

Authors
  1. Ling Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin-hua Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi-fan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu-meng Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shu Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Tao JH and Jiang S conceived and designed research. Tao JH, Shen YM, Wang L and Chen YF conducted experiments. Jiang S contributed new reagents or analytical tools. Tao JH, Shen YM and Jiang S analyzed data. Tao JH, Wang L, Chen YF and Shen YM wrote the manuscript. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Jin-hua Tao.

Additional information

Conflict of Interest

The authors have declared that there is no conflict of interest.

Supported by the National Natural Science Foundation of China (No. 81974518), Natural Science Foundation of Jiangsu Province (No. 19KJB360019) and Innovative Training Program for College Students in Jiangsu Province (No. 202010304125Y)

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, L., Tao, Jh., Chen, Yf. et al. Lizhong Decoction Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling. Chin. J. Integr. Med. 28, 1015–1022 (2022). https://doi.org/10.1007/s11655-021-3299-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-021-3299-4

Keywords

Search

Navigation