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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Qingchang Mixture Prevents the Intestinal Ischemia-reperfusion Injury through TLR4/NF-kB Pathway

Author(s): Meng Wang, Yong Zhu, Shujuan Liu, Zhaochun Tian, Pengfei Zhu, Yunjie Zhang* and Yongkun Zhou*

Volume 26, Issue 1, 2023

Published on: 17 May, 2022

Page: [49 - 57] Pages: 9

DOI: 10.2174/1386207325666220328090126

Price: $65

Abstract

Object: This study aims to determine the protective effect and molecular responses of the traditional Chinese medicine Qingchang mixture on intestinal ischemia-reperfusion (IR) injury.

Methods: The rat intestinal IR model was prepared. The intestinal ischemic injury was evaluated by HE staining, biochemical assay and western blot. In addition, a human hypoxia-reoxygenation (HR) in vitro model was prepared using intestinal epithelial cells (IEC-6). The viability and apoptosis of IEC-6 cells were measured by CCK8 and apoptosis detection. TAK242 or PDTC was used as a small molecule inhibitor of TLR4 or NF-κB, respectively.

Results: Compared with the IR group, the pretreatment of the Qingchang mixture reduced the morphological damage, oxidative stress, inflammatory response, and barrier function damage of the small intestine tissue. IR significantly increased the expression of TLR4 and NF-κB, while the pretreatment of the Qingchang mixture inhibited the expression of TLR4 and NF-κB. Furthermore, the pretreatment of Qingchang mixture, TAK242, or PDTC effectively improved the viability and hindered apoptosis of the HR-induced IEC-6 cells.

Conclusions: Traditional Chinese medicine Qingchang mixture prevents intestinal IR injury through TLR4/NF-kB pathway.

Keywords: Ischemic and ischemia-reperfusion, Chinese medicine, Qingchang mixture, oxidative stress, inflammatory response, hypoperfusion.

Graphical Abstract

[1]
Silari, M. Workplace characterisation in mixed neutron-gamma fields, specific requirements and available methods at high-energy accelerators. Radiat. Prot. Dosimetry, 2007, 124(3), 230-244.
[http://dx.doi.org/10.1093/rpd/ncm395] [PMID: 17704502]
[2]
Jin, Y.; Blikslager, A.T. Intestinal ischemia-reperfusion: Root-ing for the SOCS? Dig. Dis. Sci., 2017, 62(1), 4-6.
[http://dx.doi.org/10.1007/s10620-016-4328-6] [PMID: 27830407]
[3]
Acosta, S. Mesenteric ischemia. Curr. Opin. Crit. Care, 2015, 21(2), 171-178.
[http://dx.doi.org/10.1097/MCC.0000000000000189] [PMID: 25689121]
[4]
Gonzalez, L.M.; Moeser, A.J.; Blikslager, A.T. Animal mod-els of ischemia-reperfusion-induced intestinal injury: Pro-gress and promise for translational research. Am. J. Physiol. Gastrointest. Liver Physiol., 2015, 308(2), G63-G75.
[http://dx.doi.org/10.1152/ajpgi.00112.2013] [PMID: 25414098]
[5]
de Groot, H.; Rauen, U. Ischemia-reperfusion injury: Pro-cesses in pathogenetic networks: A review. Transplant. Proc., 2007, 39(2), 481-484.
[http://dx.doi.org/10.1016/j.transproceed.2006.12.012] [PMID: 17362763]
[6]
Camara-Lemarroy, C.R. Remote ischemic preconditioning as treatment for non-ischemic gastrointestinal disorders: Beyond ischemia-reperfusion injury. World J. Gastroenterol., 2014, 20(13), 3572-3581.
[http://dx.doi.org/10.3748/wjg.v20.i13.3572] [PMID: 24707140]
[7]
Montero, M.F.; Saurim, R.; Bonservizi, W.G.; Koike, M.K.; Taha, M.O. Heart injury following intestinal ischemia reper-fusion in rats is attenuated by association of ischemic pre-conditioning and adenosine. Acta Cir. Bras., 2014, 29(Suppl. 2), 67-71.
[http://dx.doi.org/10.1590/S0102-8650201400140013] [PMID: 25229518]
[8]
Vollmar, B.; Menger, M.D. Intestinal ischemia/reperfusion: Microcirculatory pathology and functional consequences. Langenbecks Arch. Surg., 2011, 396(1), 13-29.
[http://dx.doi.org/10.1007/s00423-010-0727-x] [PMID: 21088974]
[9]
Wang, Y. Observation on the effect of Qingchang mixture retaining enema on prevention of intestinal adhesions after abdominal surgery. Shandong Medicine., 2016, 56(12), 3.
[http://dx.doi.org/10.3969/j.issn.1002-266X.2016.12.013]
[10]
Yong, Zhu GX; Wang, Meng; Rong, Baohai; Chen, Xiqi; Zhou, Yongkun application experience of qingchang mixture in recovery of gastrointestinal function after gastric cancer operation. TCM Clin. Res., 2019, 11(35), 3.
[11]
Wang, M; Ding, J Rong, BHJCJoSoIT; Medicine, W. Effect of qingchang mixture enema on plasma motilin and IL-6 in adhesive intestinal obstruction. Trad. Chinese Med., 2018.
[http://dx.doi.org/10.27282/d.cnki.gsdzu.2019.000635]
[12]
Meng, Wang Y.Z.; Wang, Y.; Rong, B.; Chen, X. Clinical Observation of Qingchang Mixture in Treating Adhesive Intes-tinal Obstruction; Chinese Society of Traditional Chinese Medicine, 2016.
[13]
O’Neill, L.A.; Golenbock, D.; Bowie, A.G. The history of Toll-like receptors - redefining innate immunity. Nat. Rev. Immunol., 2013, 13(6), 453-460.
[http://dx.doi.org/10.1038/nri3446] [PMID: 23681101]
[14]
Watson, M.J.; Ke, B.; Shen, X.D.; Gao, F.; Busuttil, R.W.; Kupiec-Weglinski, J.W.; Farmer, D.G. Intestinal ische-mia/reperfusion injury triggers activation of innate toll-like receptor 4 and adaptive chemokine programs. Transplant. Proc., 2008, 40(10), 3339-3341.
[http://dx.doi.org/10.1016/j.transproceed.2008.07.144] [PMID: 19100385]
[15]
Tatum, P.M., Jr; Harmon, C.M.; Lorenz, R.G.; Dimmitt, R.A. Toll-like receptor 4 is protective against neonatal murine is-chemia-reperfusion intestinal injury. J. Pediatr. Surg., 2010, 45(6), 1246-1255.
[http://dx.doi.org/10.1016/j.jpedsurg.2010.02.093] [PMID: 20620328]
[16]
Pope, M.R.; Hoffman, S.M.; Tomlinson, S.; Fleming, S.D. Complement regulates TLR4-mediated inflammatory re-sponses during intestinal ischemia reperfusion. Mol. Immunol., 2010, 48(1-3), 356-364.
[http://dx.doi.org/10.1016/j.molimm.2010.07.004] [PMID: 20800895]
[17]
Zhu, Q.; He, G.; Wang, J.; Wang, Y.; Chen, W.; Guo, T. Down-regulation of toll-like receptor 4 alleviates intestinal is-chemia reperfusion injury and acute lung injury in mice. Oncotarget, 2017, 8(8), 13678-13689.
[http://dx.doi.org/10.18632/oncotarget.14624] [PMID: 28099145]
[18]
Moses, T.; Wagner, L.; Fleming, S.D. TLR4-mediated Cox-2 expression increases intestinal ischemia/reperfusion-induced damage. J. Leukoc. Biol., 2009, 86(4), 971-980.
[http://dx.doi.org/10.1189/jlb.0708396] [PMID: 19564573]
[19]
Wang, J.; He, G.Z.; Wang, Y.K.; Zhu, Q.K.; Chen, W.; Guo, T. TLR4-HMGB1-, MyD88- and TRIF-dependent signaling in mouse intestinal ischemia/reperfusion injury. World J. Gastroenterol., 2015, 21(27), 8314-8325.
[http://dx.doi.org/10.3748/wjg.v21.i27.8314] [PMID: 26217083]
[20]
Terzi, A.; Coban, S.; Yildiz, F.; Ates, M.; Bitiren, M.; Taskin, A.; Aksoy, N. Protective effects of nigella sativa on intestinal ischemia-reperfusion injury in rats. J. Invest. Surg., 2010, 23(1), 21-27.
[http://dx.doi.org/10.3109/08941930903469375] [PMID: 20233001]
[21]
Mészáros, A.T.; Büki, T.; Fazekas, B.; Tuboly, E.; Horváth, K.; Poles, M.Z. Szűcs, S.; Varga, G.; Kaszaki, J.; Boros, M. Inhalation of methane preserves the epithelial barrier during ischemia and reperfusion in the rat small intestine. Surgery, 2017, 161(6), 1696-1709.
[http://dx.doi.org/10.1016/j.surg.2016.12.040] [PMID: 28242089]
[22]
Inoue, K.; Oyamada, M.; Mitsufuji, S.; Okanoue, T.; Taka-matsu, T. Different changes in the expression of multiple kinds of tight-junction proteins during ischemia-reperfusion injury of the rat ileum. Acta Histochem. Cytochem., 2006, 39(2), 35-45.
[http://dx.doi.org/10.1267/ahc.05048] [PMID: 17375208]
[23]
Li, Q.; Zhang, Q.; Wang, C.; Liu, X.; Qu, L.; Gu, L.; Li, N.; Li, J. Altered distribution of tight junction proteins after intes-tinal ischaemia/reperfusion injury in rats. J. Cell. Mol. Med., 2009, 13(9B), 4061-4076.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00975.x] [PMID: 19929946]
[24]
Watanabe, T.; Higuchi, K.; Kobata, A.; Nishio, H.; Tanigawa, T.; Shiba, M.; Tominaga, K.; Fujiwara, Y.; Oshitani, N.; Asa-hara, T.; Nomoto, K.; Takeuchi, K.; Arakawa, T. Non-steroidal anti-inflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent. Gut, 2008, 57(2), 181-187.
[http://dx.doi.org/10.1136/gut.2007.125963] [PMID: 17639086]
[25]
Tian, S.; Guo, R.; Wei, S.; Kong, Y.; Wei, X.; Wang, W.; Shi, X.; Jiang, H. Curcumin protects against the intestinal ische-mia-reperfusion injury: Involvement of the tight junction pro-tein ZO-1 and TNF-α related mechanism. Korean J. Physiol. Pharmacol., 2016, 20(2), 147-152.
[http://dx.doi.org/10.4196/kjpp.2016.20.2.147] [PMID: 26937210]
[26]
Gu, L.; Li, N.; Yu, W.; Gong, J.; Li, Q.; Zhu, W.; Li, J. Ber-berine reduces rat intestinal tight junction injury induced by ischemia-reperfusion associated with the suppression of in-ducible nitric oxide synthesis. Am. J. Chin. Med., 2013, 41(6), 1297-1312.
[http://dx.doi.org/10.1142/S0192415X13500870] [PMID: 24228602]
[27]
Shen, Z.Y.; Zhang, J.; Song, H.L.; Zheng, W.P. Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism. World J. Gastroenterol., 2013, 19(23), 3583-3595.
[http://dx.doi.org/10.3748/wjg.v19.i23.3583] [PMID: 23801859]
[28]
Yang, W.J.; Juan, L.I.; Zhang, C. Effect of jianwei qingchang mixture on intestinal movement and gastric mucosa of mice. Gansu J. Traditional Chinese Med., 2012, 25, 20-22.
[29]
Thoma-Uszynski, S.; Stenger, S.; Takeuchi, O.; Ochoa, M.T.; Engele, M.; Sieling, P.A.; Barnes, P.F.; Rollinghoff, M.; Bolcskei, P.L.; Wagner, M.; Akira, S.; Norgard, M.V.; Belisle, J.T.; Godowski, P.J.; Bloom, B.R.; Modlin, R.L. Induction of direct antimicrobial activity through mammalian toll-like re-ceptors. Science, 2001, 291(5508), 1544-1547.
[http://dx.doi.org/10.1126/science.291.5508.1544] [PMID: 11222859]
[30]
Medzhitov, R.; Preston-Hurlburt, P.; Janeway, C.A. Jr A hu-man homologue of the Drosophila Toll protein signals activa-tion of adaptive immunity. Nature, 1997, 388(6640), 394-397.
[http://dx.doi.org/10.1038/41131] [PMID: 9237759]
[31]
Wang, F.; Li, Q.; Wang, C.; Tang, C.; Li, J. Dynamic alteration of the colonic microbiota in intestinal ischemia-reperfusion injury. PLoS One, 2012, 7(7)e42027
[http://dx.doi.org/10.1371/journal.pone.0042027] [PMID: 22848694]
[32]
Wu, H.; Deng, Y.Y.; Liu, L.; Tan, Q.H.; Wang, C.H.; Guo, M.M.; Xie, Y.M.; Tang, C.W. Intestinal ischemia-reperfusion of macaques triggers a strong innate immune response. World J. Gastroenterol., 2014, 20(41), 15327-15334.
[http://dx.doi.org/10.3748/wjg.v20.i41.15327] [PMID: 25386081]
[33]
Wu, H.; Liu, L.; Tan, Q.; Wang, C.; Guo, M.; Xie, Y.; Tang, C. Somatostatin limits intestinal ischemia-reperfusion injury in macaques via suppression of TLR4-NF-kappaB cytokine pathway. J. Gastrointest. Surg., 2009, 13(5), 983-993.
[http://dx.doi.org/10.1007/s11605-009-0816-8] [PMID: 19184243]
[34]
Nadatani, Y.; Watanabe, T.; Shimada, S.; Otani, K.; Tanigawa, T.; Fujiwara, Y. Microbiome and intestinal ische-mia/reperfusion injury. J. Clin. Biochem. Nutr., 2018, 63(1), 26-32.
[http://dx.doi.org/10.3164/jcbn.17-137] [PMID: 30087540]

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