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Article

Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway

  • Authors:
    • Ke Zhang
    • Xian Fa Jiao
    • Jin Xiu Li
    • Xiao Wen Wang
  • View Affiliations / Copyright

    Affiliations: Department of Critical Care Medicine, Zhengzhou People's Hospital, Zhengzhou, Henan 450053, P.R. China
  • Pages: 4415-4421
    |
    Published online on: June 12, 2015
       https://doi.org/10.3892/mmr.2015.3925
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Abstract

Sepsis is one of the leading causes of mortality in severe systemic inflammatory syndrome. The endotoxin-induced inflammatory response has been linked to the development of sepsis. Rhein is a lipophilic anthraquinone isolated from Rheum rhabarbarum (rhubarb), which has a protective effect on intestinal damage in vivo. However, the underlying mechanism responsible for the protective effects of rhein remains to be elucidated. In the present study, mice were exposed to 20 mg/kg lipopolysaccharide (LPS), prior to being treated with either 100 mg/kg rhein or 0.3 mg/kg toll‑like receptor 4 (TLR4) signaling inhibitor TAK‑242. In the rhein‑treated mice, the colon length (cm) was extended and colon injury was attenuated. In addition, treatment with rhein significantly decreased the expression levels of the LPS‑induced inflammatory cytokines interleukin (IL)‑1β, IL‑6, IL‑8, and tumor necrosis factor‑α, in both the plasma and colon tissue. However, mice treated with TAK‑242 exhibited increased expression levels of IL‑10, as determined by ELISA and western blot analysis. In addition, immunohistochemistry and western blot analyses demonstrated that treatment with rhein was able to reduce TLR4 expression and inhibit nuclear factor‑κB (NF‑κB) phosphorylation in colon tissue. Furthermore, LPS induction was blocked by TAK‑242. These results demonstrate that the observed rhein‑attenuated inflammatory response during sepsis may be achieved via the TLR4 NF‑κB signaling pathway. In conclusion, the results of the present study provide a novel insight into the protective effects of rhein on LPS‑induced intestinal inflammation, and demonstrate that rhein may act as a beneficial therapeutic agent in the treatment of sepsis-induced intestinal damage.
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1 

Rajkumari N, Mathur P, Sharma S, Gupta B, Bhoi S and Misra MC: Procalcitonin as a predictor of sepsis and outcome in severe trauma patients: A prospective study. J Lab Physicians. 5:100–108. 2013. View Article : Google Scholar

2 

Duran-Bedolla J, Montes de Oca-Sandoval MA, Saldaña-Navor V, Villalobos-Silva JA, Rodriguez MC and Rivas-Arancibia S: Sepsis, mitochondrial failure and multiple organ dysfunction. Clin Invest Med. 37:E58–E69. 2014.PubMed/NCBI

3 

Hatakeyama N and Matsuda N: Mechanisms of inflammatory response and organ dysfunction: Organ-protective strategy by anesthetics. Curr Pharm Des. Feb 3–2014.Epub ahead of print. View Article : Google Scholar

4 

Luo HM, Du MH, Lin ZL, et al: Valproic acid treatment inhibits hypoxia-inducible factor 1α accumulation and protects against burn-induced gut barrier dysfunction in a rodent model. PLoS One. 8:e775232013. View Article : Google Scholar

5 

Fink MP: Intestinal epithelial hyperpermeability: Update on the pathogenesis of gut mucosal barrier dysfunction in critical illness. Curr Opin Crit Care. 9:143–151. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Chatterjee N, Das S, Bose D, Banerjee S, Jha T and Saha KD: Leishmanial lipid suppresses the bacterial endotoxin-induced inflammatory response with attenuation of tissue injury in sepsis. J Leukoc Biol. 96:325–336. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Fatemi K, Radvar M, Rezaee A, et al: Comparison of relative TLR-2 and TLR-4 expression level of disease and healthy gingival tissue of smoking and non-smoking patients and periodontally healthy control patients. Aust Dent J. 58:315–320. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Musie E, Moore CC, Martin EN and Scheld WM: Toll-like receptor 4 stimulation prior to or after Streptococcus pneumoniae induced sepsis improves survival and is dependent on T-cells. PLoS One. 9:e860152014. View Article : Google Scholar

9 

Yang JC, Wu SC, Rau CS, et al: Inhibition of the phosphoinositide 3-kinase pathway decreases innate resistance to lipopolysaccharide toxicity in TLR4 deficient mice. J Biomed Sci. 21:202014. View Article : Google Scholar : PubMed/NCBI

10 

Mascolo N, Autore G, Izzo AA, Biondi A and Capasso F: Effects of senna and its active compounds rhein and rhein-anthrone on PAF formation by rat colon. J Pharm Pharmacol. 44:693–695. 1992. View Article : Google Scholar : PubMed/NCBI

11 

Raimondi F, Santoro P, Maiuri L, et al: Reactive nitrogen species modulate the effects of rhein, an active component of senna laxatives, on human epithelium in vitro. J Pediatr Gastroenterol Nutr. 34:529–534. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Peng SN, Zeng HH, Fu AX, Chen XW and Zhu QX: Effects of rhein on intestinal epithelial tight junction in IgA nephropathy. World J Gastroenterol. 19:4137–4145. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Zhang Q, Ma YM, Wang ZT and Wang CH: Differences in pharmacokinetics and anti-inflammatory effects between decoction and maceration of Sanhuang Xiexin Tang in rats and mice. Planta Med. 79:1666–1673. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Guo MZ, Li XS, Xu HR, Mei ZC, Shen W and Ye XF: Rhein inhibits liver fibrosis induced by carbon tetrachloride in rats. Acta Pharmacol Sin. 23:739–744. 2002.PubMed/NCBI

15 

Ni JQ, Ouyang Q, Lin L, et al: Role of toll-like receptor 4 on lupus lung injury and atherosclerosis in LPS-challenge ApoE−/−mice. Clin Dev Immunol. 2013:4768562013. View Article : Google Scholar

16 

Kim WH, Song HO, Jin CM, et al: The methanol extract of Azadirachta indica A. juss leaf protects mice against lethal endotoxemia and sepsis. Biomol Ther (Seoul). 20:96–103. 2012. View Article : Google Scholar

17 

Chiu CJ, McArdle AH, Brown R, Scott HJ and Gurd FN: Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg. 101:478–483. 1970. View Article : Google Scholar : PubMed/NCBI

18 

Cordioli RL, Cordioli E, Negrini R and Silva E: Sepsis and pregnancy: Do we know how to treat this situation? Rev Bras Ter Intensiva. 25:334–344. 2013. View Article : Google Scholar

19 

Van Leeuwen PA, Boermeester MA, Houdijk AP, et al: Clinical significance of translocation. Gut. 35(Suppl 1): 28–S34. 1994. View Article : Google Scholar

20 

Cross AS, Sidberry H and Sadoff JC: The human antibody response during natural bacteremic infection with gram-negative bacilli against lipopolysaccharide core determinants. J Infect Dis. 160:225–236. 1989. View Article : Google Scholar : PubMed/NCBI

21 

Piazza O, Pulcrano G, Fiori PL, et al: Toll-like receptor kinetics in septic shock patients: A preliminary study. Int J Immunopathol Pharmacol. 25:425–433. 2012.PubMed/NCBI

22 

Drago-Serrano ME, de la Garza-Amaya M, Luna JS and Campos-Rodríguez R: Lactoferrin-lipopolysaccharide (LPS) binding as key to antibacterial and antiendotoxic effects. Int Immunopharmacol. 12:1–9. 2012. View Article : Google Scholar

23 

Verstak B, Stack J, Ve T, et al: The TLR signaling adaptor TRAM interacts with TRAF6 to mediate activation of the inflammatory response by TLR4. J Leukoc Biol. 96:427–436. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Gao Y, Chen X, Fang L, et al: Rhein exerts pro- and anti-inflammatory actions by targeting IKKβ inhibition in LPS-activated macrophages. Free Radic Biol Med. 72:104–112. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Sautner T, Wessely C, Riegler M, et al: Early effects of catecholamine therapy on mucosal integrity, intestinal blood flow, and oxygen metabolism in porcine endotoxin shock. Ann Surg. 228:239–248. 1998. View Article : Google Scholar : PubMed/NCBI

26 

Redondo AC, Ceccon ME, Silveira-Lessa AL, et al: TLR-2 and TLR-4 expression in monocytes of newborns with late-onset sepsis. J Pediatr (Rio J). 90:472–478. 2014. View Article : Google Scholar

27 

Wang Q, Wang JJ, Boyce S, Fischer JE and Hasselgren PO: Endotoxemia and IL-1 beta stimulate mucosal IL-6 production in different parts of the gastrointestinal tract. J Surg Res. 76:27–31. 1998. View Article : Google Scholar : PubMed/NCBI

28 

Ueda Y, Kayama H, Jeon SG, et al: Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages via the production of IL-10. Int Immunol. 22:953–962. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Paul G, Khare V and Gasche C: Inflamed gut mucosa: Downstream of interleukin-10. Eur J Clin Invest. 42:95–109. 2012. View Article : Google Scholar

30 

Im E, Riegler FM, Pothoulakis C and Rhee SH: Elevated lipopolysaccharide in the colon evokes intestinal inflammation, aggravated in immune modulator-impaired mice. Am J Physiol Gastrointest Liver Physiol. 303:G490–G497. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Chung YW, Choi JH, Oh TY, Eun CS and Han DS: Lactobacillus casei prevents the development of dextran sulphate sodium-induced colitis in Toll-like receptor 4 mutant mice. Clin Exp Immunol. 151:182–189. 2008. View Article : Google Scholar

32 

Teo JD, Macary PA and Tan KS: Pleiotropic effects of Blastocystis spp. Subtypes 4 and 7 on ligand-specific toll-like receptor signaling and NF-κB activation in a human monocyte cell line. PLoS One. 9:e890362014. View Article : Google Scholar

33 

Lee JH, Lee B, Lee HS, et al: Lactobacillus suntoryeus inhibits pro-inflammatory cytokine expression and TLR-4-linked NF-kappaB activation in experimental colitis. Int J Colorectal Dis. 24:231–237. 2009. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Zhang K, Jiao XF, Li JX and Wang XW: Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway. Mol Med Rep 12: 4415-4421, 2015.
APA
Zhang, K., Jiao, X.F., Li, J.X., & Wang, X.W. (2015). Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway. Molecular Medicine Reports, 12, 4415-4421. https://doi.org/10.3892/mmr.2015.3925
MLA
Zhang, K., Jiao, X. F., Li, J. X., Wang, X. W."Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway". Molecular Medicine Reports 12.3 (2015): 4415-4421.
Chicago
Zhang, K., Jiao, X. F., Li, J. X., Wang, X. W."Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway". Molecular Medicine Reports 12, no. 3 (2015): 4415-4421. https://doi.org/10.3892/mmr.2015.3925
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang K, Jiao XF, Li JX and Wang XW: Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway. Mol Med Rep 12: 4415-4421, 2015.
APA
Zhang, K., Jiao, X.F., Li, J.X., & Wang, X.W. (2015). Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway. Molecular Medicine Reports, 12, 4415-4421. https://doi.org/10.3892/mmr.2015.3925
MLA
Zhang, K., Jiao, X. F., Li, J. X., Wang, X. W."Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway". Molecular Medicine Reports 12.3 (2015): 4415-4421.
Chicago
Zhang, K., Jiao, X. F., Li, J. X., Wang, X. W."Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway". Molecular Medicine Reports 12, no. 3 (2015): 4415-4421. https://doi.org/10.3892/mmr.2015.3925
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