Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Modified Renshen Wumei Decoction Alleviates Intestinal Barrier Destruction in Rats with Diarrhea

  • Guan, Zhiwei (Hospital of Chengdu University of Traditional Chinese Medicine) ;
  • Zhao, Qiong (Hospital of Chengdu University of Traditional Chinese Medicine) ;
  • Huang, Qinwan (College of Pharmacy, Chengdu University of Traditional Chinese Medicine) ;
  • Zhao, Zhonghe (Hospital of Chengdu University of Traditional Chinese Medicine) ;
  • Zhou, Hongyun (The First Affiliated Hospital of Henan University of Traditional Chinese Medicine) ;
  • He, Yuanyuan (Hospital of Chengdu University of Traditional Chinese Medicine) ;
  • Li, Shanshan (Hospital of Chengdu University of Traditional Chinese Medicine) ;
  • Wan, Shifang (Hospital of Chengdu University of Traditional Chinese Medicine)
  • Received : 2021.06.14
  • Accepted : 2021.07.19
  • Published : 2021.09.28
Download PDF
⟨ Previous Next ⟩

Abstract

Modified Renshen Wumei decoction (MRWD), a famous traditional Chinese medicine, is widely used for treating persistent diarrhea. However, as the mechanism by which MRWD regulates diarrhea remains unknown, we examined the protective effects of MRWD on intestinal barrier integrity in a diarrhea model. In total, 48 male rats were randomly distributed to four treatment groups: the blank group (CK group), model group (MC group), Medilac-Vita group (MV group) and Chinese herb group (MRWD group). After a 21-day experiment, serum and colon samples were assessed. The diarrhea index, pathological examination findings and change in ᴅ-lactate and diamine oxidase (DAO) contents illustrated that the induction of diarrhea caused intestinal injury, which was ameliorated by MV and MRWD infusion. Metabolomics analysis identified several metabolites in the serum. Some critical metabolites, such as phosphoric acid, taurine, cortisone, leukotriene B4 and calcitriol, were found to be significantly elevated by MRWD infusion. Importantly, these differences correlated with mineral absorption and metabolism and peroxisome proliferator-activated receptor (PPAR) pathways. Moreover, it significantly increased the expression levels of TLR4, MyD88 and p-NF-κB p65 proteins and the contents of IL-1 and TNF-α, while the expression levels of occludin, claudin-1 and ZO-1 proteins decreased. These deleterious effects were significantly alleviated by MV and MRWD infusion. Our findings indicate that MRWD infusion helps alleviate diarrhea, possibly by maintaining electrolyte homeostasis, improving the intestinal barrier integrity, and inhibiting the TLR4/NF-κB axis.

Keywords

Acknowledgement

This research was supported by the National Natural Science Foundation of China (81102544, 81373531, 81674026).

References

  1. Groschwitz KR, Hogan SP. 2010. Intestinal barrier function: molecular regulation and disease pathogenesis. J. Allergy Clin. Immunol. 124: 3-20. https://doi.org/10.1016/j.jaci.2009.05.038
  2. Chelakkot C, Ghim J, Sung HR. 2018. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp. Mol. Med. 50: 103.
  3. Maaike, V, Severine V. 2017. The intestinal barrier: a fundamental role in health and disease. Expert Rev. Gastroenterol. Hepatol. 11: 821-834. https://doi.org/10.1080/17474124.2017.1343143
  4. Wan J, Zhang J, Chen DW, Yu B, Huang ZQ, Mao XB, et al. 2018. Alginate oligosaccharide enhances intestinal integrity of weaned pigs through altering intestinal inflammatory responses and antioxidant status. RSC Adv. 8: 13482-13492. https://doi.org/10.1039/C8RA01943F
  5. Konig J, Wells J, Cani PD, Garcia-Rodenas C, MacDonald T, Mercenier A, et al. 2016. Human intestinal barrier function in health and disease. Clin. Transl. Gastroen. 7: e196. https://doi.org/10.1038/ctg.2016.54
  6. Sarmin M, Hossain MI, Islam SB, Alam NH, Sarker SA, Islam MM, et al. 2020. Efficacy of a green banana-mixed diet in the management of persistent diarrhea: protocol for an open-labeled, randomized controlled trial. JMIR Res. Protoc. 9: e15759. https://doi.org/10.2196/15759
  7. Shafiqul S, Tahmeed A, Harald B. 2017. Persistent diarrhea: a persistent infection with enteropathogens or a gut commensal dysbiosis?. Environ. Microbiol. 19: 3789-3801. https://doi.org/10.1111/1462-2920.13873
  8. Mahalanabis D, Alam AN, Rahman N, Hasnat A. 1991. Prognostic indicators and risk factors for increased duration of acute diarrhoea and for persistent diarrhoea in children. Int. J. Epidemiol. 20: 1064-1072. https://doi.org/10.1093/ije/20.4.1064
  9. Jeanette M, Sommer C, Olsen TM, Iversen P, Gustav A, Seth J, et al. 2018. Persistent symptoms in patients with Crohn's disease in remission: an exploratory study on the role of diet. Scand. J. Gastroenterol. 53: 573-578. https://doi.org/10.1080/00365521.2017.1397736
  10. Bandsma R, Sadiq K, Bhutta Z. 2020. Persistent diarrhoea: current knowledge and novel concepts. Paediatr. Int. Child Health 39: 41-47. https://doi.org/10.1080/20469047.2018.1504412
  11. Liu YL, Liu KL, Yang M, Han Y, Zhang Q, Conde J, et al. 2019. Gastric parietal cell and intestinal goblet cell secretion: a novel cell-mediated in vivo metal nanoparticle metabolic pathway enhanced with diarrhea via Chinese herbs. Nanoscale Res. Lett. 14: 79. https://doi.org/10.1186/s11671-019-2908-z
  12. Lin XW, Liu X, Xu JJ, Cheng KK, Cao JN, Liu T, et al. 2019. Metabolomics analysis of herb-partitioned moxibustion treatment on rats with diarrhea-predominant irritable bowel syndrome. Chin. Med. 14: 18. https://doi.org/10.1186/s13020-019-0240-2
  13. Li SS, Qi YL, Chen LX, Qu D, Li ZM, Gao K, et al. 2019. Effects of Panax ginseng polysaccharides on the gut microbiota in mice with antibiotic-associated diarrhea. Int. J. Biol. Macromol. 124: 931-937. https://doi.org/10.1016/j.ijbiomac.2018.11.271
  14. Ding XJ, Sun XL, Yu XF, Zhao ST, Yang Y, Xu WJ, et al. 2019. The effects of wumei pill on intestinal flora and neurotransmitters in rats with diarrhea-predominant irritable bowel syndrome (IBS-D). AIP. Conf. Proc. 2079: 020028.
  15. Laura R, Long J, Thorsten C. 2020. Barrier integrity and chronic inflammation mediated by HIF-1 impact on intestinal tumorigenesis. Cancer Lett. 490:186-192. https://doi.org/10.1016/j.canlet.2020.07.002
  16. Assadiana A, Assadianb O, Senekowitsch C, Rotter R, Bahrami S, Furst W, et al. 2006. Plasma D-lactate as a potential early marker for colon ischaemia after open aortic reconstruction. Eur. J. Vas. Endovasc. 31: 470-474. https://doi.org/10.1016/j.ejvs.2005.10.031
  17. Hui S, Wu BY, Wan J, Liu WH, Su BB. 2015. The role of serum intestinal fatty acid binding protein levels and D-lactate levels in the diagnosis of acute intestinal ischemia. Clin. Res. Hepatol. Gas. 39: 373-378. https://doi.org/10.1016/j.clinre.2014.12.005
  18. Fukudaa T, Tsukanoa K, Nakatsuji H, Suzuki K. 2019. Plasma diamine oxidase activity decline with diarrhea severity in calves indicating systemic dysfunction related to intestinal mucosal damage. Res. Vet. Sci. 126: 127-130. https://doi.org/10.1016/j.rvsc.2019.08.027
  19. Cathleen MC, Emily JO, Keely GM, Allie ES, Anne MS, Kristen MS, et al. 2020. Small bowel resection increases paracellular gut barrier permeability via alterations of tight junction complexes mediated by intestinal TLR4. J. Sur. Res. 258: 73-81. https://doi.org/10.1016/j.jss.2020.08.049
  20. Anica SB, Moorthy K, Fan S, Jimenz J, R Hernande, Gibson K, et al. 2019. The JAK-inhibitor tofacitinib rescues human intestinal epithelial cells and colonoids from cytokine-induced barrier dysfunction. Inflamm. Bowel Dis. 26: 407-422. https://doi.org/10.1093/ibd/izz266
  21. Zhao R, Long X, Yang J, Du L, Zhang X, Li J, et al. 2019. Pomegranate peel polyphenols reduce chronic low-grade inflammatory responses by modulating gut microbiota and decreasing colonic tissue damage in rats fed a high-fat diet. Food Funct. 10: 8273-8285. https://doi.org/10.1039/C9FO02077B
  22. Li Q, Li K, Hu T, Liu F, Liao S, Zou Y. 2021. 6,7-Dihydroxy-2,4-Dimethoxyphenanthrene from Chinese yam peels alleviates DSS-induced intestinal mucosal injury in mice via modulation of the NF-κB/COX-2 signaling pathway. J. Agric. Food Chem. 69: 4720-4731. https://doi.org/10.1021/acs.jafc.1c00487
  23. Beheshtipour J, Raeeszadeh M. 2020. Evaluation of interleukin-10 and pro-inflammatory cytokine profile in calves naturally infected with neonatal calf diarrhea syndrome. Arch. Razi Inst. 75: 213-218.
  24. Wu X, Gao LM, Liu YL, Xie CY. 2020. Maternal dietary uridine supplementation reduces diarrhea incidence in piglets by regulating the intestinal mucosal barrier and cytokine profiles. J. Sci. Food Agr. 100: 3709-3718. https://doi.org/10.1002/jsfa.10410
  25. Sadi RA, Ye DM, Said HM, Ma TY. 2010. IL-1β-induced increase in intestinal epithelial tight junction permeability is mediated by MEKK-1 activation of canonical NF-κB pathway. Am. J. Pathol. 177: 2310-2322. https://doi.org/10.2353/ajpath.2010.100371
  26. Capaldo CT, Nusrat A. 2009. Cytokine regulation of tight junctions. Biochim. Biophys. Acta 1788: 864-871. https://doi.org/10.1016/j.bbamem.2008.08.027
  27. Sadi RA, Boivin M, Ma T. 2013. Mechanism of cytokine modulation of epithelial tight junction barrier. Front. Biosci. 14: 2765-2778.
  28. Kim HK. 2018. Do Toll-like receptors play a new role as a biomarker of irritable bowel syndrome?. J. Neurogastroenterol. 24: 510-511. https://doi.org/10.5056/jnm18153
  29. Nikolay K, Konstantin S, Vladimir C, Porozov Y, Savateeva-Lyubimova, T, Peri Francesco. 2017. TLR4 signaling pathway modulators as potential therapeutics in inflammation and sepsis. Vaccines 5: 34. https://doi.org/10.3390/vaccines5040034
  30. Peri F, Granucci F, Weiss J. 2015. Endotoxin, TLR4 signaling and beyond. Mol. Immunol. 63: 125-126. https://doi.org/10.1016/j.molimm.2014.09.001
  31. Wardill HR, Bowen JM, Van Sebille YZ, Kate RS, Janet KC, Imogen AB, et al. 2016. TLR4-dependent claudin-1 internalization and secretagogue-mediated chloride secretion regulate irinotecan-induced diarrhea. Mol. Cancer Ther. 15: 2767. https://doi.org/10.1158/1535-7163.MCT-16-0330
  32. Meng X, Hu W, Wu S, Zhu Z, Lu R, Yang G, et al. 2019. Chinese yam peel enhances the immunity of the common carp (Cyprinus carpio L.) by improving the gut defence barrier and modulating the intestinal microflora. Fish Shellfish Immunmol. 95: 528-537. https://doi.org/10.1016/j.fsi.2019.10.066
  33. Du L, Li J, Zhang X, Wang L, Zhang W, Yang M., et al. 2019. Pomegranate peel polyphenols inhibits inflammation in LPS-induced RAW264.7 macrophages via the suppression of TLR4/NF-κB pathway activation. Food Nutr. Res. 63. doi: 10.29219/fnr.v63.3392.
  34. Kim N, Ryu S, Hwang B, Park S, Kim Y, Hong J, et al. 2012. 1-Dehydro-[10]-gingerdione from ginger inhibits IKKβ activity for NF-κB activation and suppresses NF-κB-regulated expression of inflammatory genes. Br. J. Pharmacol. 167: 128-140. https://doi.org/10.1111/j.1476-5381.2012.01980.x
  35. Suastegui JM, Leiva JS, Teles A, Dariel TR. 2020. Evaluation of homeopathic phosphoric acid, silica and pathogenic vibrio on digestive enzyme activity of longfin yellowtail fish (Seriola rivoliana). Homeopathy 109: 3-13. https://doi.org/10.1055/s-0039-1692998
  36. Kirby BJ, Ryan BA, Berit SK, St-Arnaud R, Kovacs CS. 2019. Intestinal calcium absorption upregulates during lactation without the vitamin D receptor (VDR) but is downregulated without calcitriol: evidence of an alternate receptor?. Calcif. Tissue Int. 104: S101.
  37. Monsalve FA, Pyarasani RD, Lopez FD, Rodrigo MC. 2013. Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases. Mediators Inflamm. 2013: 539627.
  38. Su CG, Wen X, Bailey ST, Jiang W, Rangwala SM, Keilbaugh,SA, et al. 1999. A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J. Clin. Invest. 104: 383-389. https://doi.org/10.1172/JCI7145