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Acanthopanax senticosus polysaccharides-induced intestinal tight junction injury alleviation via inhibition of NF-κB/MLCK pathway in a mouse endotoxemia model.
World J Gastroenterol. 2017 Mar 28; 23(12):2175-2184.WJ

Abstract

AIM

To examine the effects of Acanthopanax senticosus polysaccharides (ASPS) on intestinal tight junction (TJ) disruption and nuclear factor-kappa B (NF-κB)/myosin light chain kinase (MLCK) activation in endotoxemia.

METHODS

BALB/C mice (6-8-weeks-old) received continuous intragastric gavage of ASPS for 7 d before injection of lipopolysaccharide (LPS), or received ASPS once after LPS injection. Blood and intestinal mucosal samples were collected 6 h after LPS challenge. Clinical symptoms, histological injury, intestinal permeability, TJ ultrastructure, and TJ protein expression were determined.

RESULTS

Compared with mice in the LPS group, pretreatment with ASPS improved clinical and histological scores by 390.9% (P < 0.05) and 57.89% (P < 0.05), respectively, and gut permeability change in endotoxemic mice was shown by a 61.93% reduction in reduced leakage of fluorescein isothiocyanate-dextran 6 h after LPS injection (P < 0.05). ASPS pretreatment also prevented LPS-induced TJ ultrastructure breakdown supported by increased electron dense materials between adjoining cells, sustained redistribution and expression of occludin (0.597 ± 0.027 vs 0.103 ± 0.009, P < 0.05) and zonula occludens-1 (0.507 ± 0.032 vs 0.125 ± 0.019, P < 0.05), and suppressed activation of the NF-κB/MLCK pathway indicated by reduced expression of NF-κB, phospho-inhibitor kappa B-alpha, MLCK and phospho-myosin light-chain-2 by 16.06% (P < 0.05), 54.31% (P < 0.05), 66.10% (P < 0.05) and 64.82% (P < 0.05), respectively.

CONCLUSION

ASPS pretreatment may be associated with inhibition of the NF-κB/MLCK pathway and concomitant amelioration of LPS-induced TJ dysfunction of intestinal epithelium in endotoxemia.

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Authors+Show Affiliations

Han J
Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
Li JH
Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
Bai G
Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
Shen GS
Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
Chen J
Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
Liu JN
Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
Wang S
Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.
Liu XJ
Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China.

MeSH

AnimalsCell Membrane PermeabilityCell NucleusCytoplasmEleutherococcusEndotoxemiaIntestinal MucosaIntestinesLipopolysaccharidesMaleMiceMice, Inbred BALB CMyosin-Light-Chain KinaseNF-kappa BPermeabilityPolysaccharidesSignal TransductionTight Junctions

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28405145

Citation

Han, Jie, et al. "Acanthopanax Senticosus Polysaccharides-induced Intestinal Tight Junction Injury Alleviation Via Inhibition of NF-κB/MLCK Pathway in a Mouse Endotoxemia Model." World Journal of Gastroenterology, vol. 23, no. 12, 2017, pp. 2175-2184.
Han J, Li JH, Bai G, et al. Acanthopanax senticosus polysaccharides-induced intestinal tight junction injury alleviation via inhibition of NF-κB/MLCK pathway in a mouse endotoxemia model. World J Gastroenterol. 2017;23(12):2175-2184.
Han, J., Li, J. H., Bai, G., Shen, G. S., Chen, J., Liu, J. N., Wang, S., & Liu, X. J. (2017). Acanthopanax senticosus polysaccharides-induced intestinal tight junction injury alleviation via inhibition of NF-κB/MLCK pathway in a mouse endotoxemia model. World Journal of Gastroenterology, 23(12), 2175-2184. https://doi.org/10.3748/wjg.v23.i12.2175
Han J, et al. Acanthopanax Senticosus Polysaccharides-induced Intestinal Tight Junction Injury Alleviation Via Inhibition of NF-κB/MLCK Pathway in a Mouse Endotoxemia Model. World J Gastroenterol. 2017 Mar 28;23(12):2175-2184. PubMed PMID: 28405145.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acanthopanax senticosus polysaccharides-induced intestinal tight junction injury alleviation via inhibition of NF-κB/MLCK pathway in a mouse endotoxemia model. AU - Han,Jie, AU - Li,Ji-Hong, AU - Bai,Guang, AU - Shen,Guo-Shun, AU - Chen,Jing, AU - Liu,Jia-Nan, AU - Wang,Shuo, AU - Liu,Xian-Jun, PY - 2016/12/09/received PY - 2017/01/18/revised PY - 2017/02/16/accepted PY - 2017/4/14/entrez PY - 2017/4/14/pubmed PY - 2017/12/2/medline KW - Acanthopanax senticosus polysaccharide KW - Intestinal permeability KW - Myosin light chain kinase KW - Nuclear factor-kappa B KW - Tight junction SP - 2175 EP - 2184 JF - World journal of gastroenterology JO - World J Gastroenterol VL - 23 IS - 12 N2 - AIM: To examine the effects of Acanthopanax senticosus polysaccharides (ASPS) on intestinal tight junction (TJ) disruption and nuclear factor-kappa B (NF-κB)/myosin light chain kinase (MLCK) activation in endotoxemia. METHODS: BALB/C mice (6-8-weeks-old) received continuous intragastric gavage of ASPS for 7 d before injection of lipopolysaccharide (LPS), or received ASPS once after LPS injection. Blood and intestinal mucosal samples were collected 6 h after LPS challenge. Clinical symptoms, histological injury, intestinal permeability, TJ ultrastructure, and TJ protein expression were determined. RESULTS: Compared with mice in the LPS group, pretreatment with ASPS improved clinical and histological scores by 390.9% (P < 0.05) and 57.89% (P < 0.05), respectively, and gut permeability change in endotoxemic mice was shown by a 61.93% reduction in reduced leakage of fluorescein isothiocyanate-dextran 6 h after LPS injection (P < 0.05). ASPS pretreatment also prevented LPS-induced TJ ultrastructure breakdown supported by increased electron dense materials between adjoining cells, sustained redistribution and expression of occludin (0.597 ± 0.027 vs 0.103 ± 0.009, P < 0.05) and zonula occludens-1 (0.507 ± 0.032 vs 0.125 ± 0.019, P < 0.05), and suppressed activation of the NF-κB/MLCK pathway indicated by reduced expression of NF-κB, phospho-inhibitor kappa B-alpha, MLCK and phospho-myosin light-chain-2 by 16.06% (P < 0.05), 54.31% (P < 0.05), 66.10% (P < 0.05) and 64.82% (P < 0.05), respectively. CONCLUSION: ASPS pretreatment may be associated with inhibition of the NF-κB/MLCK pathway and concomitant amelioration of LPS-induced TJ dysfunction of intestinal epithelium in endotoxemia. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/28405145/Acanthopanax_senticosus_polysaccharides_induced_intestinal_tight_junction_injury_alleviation_via_inhibition_of_NF_κB/MLCK_pathway_in_a_mouse_endotoxemia_model_ DB - PRIME DP - Unbound Medicine ER -