Astragaloside IV ameliorates necrotizing enterocolitis by attenuating oxidative stress and suppressing inflammation via the vitamin D3-upregulated protein 1/NF-κB signaling pathway

Cai,Zhiyong; Liu,Jindi; Bian,Hongliang; Cai,Jinlan

doi:10.3892/etm.2016.3629

Astragaloside IV ameliorates necrotizing enterocolitis by attenuating oxidative stress and suppressing inflammation via the vitamin D3-upregulated protein 1/NF-κB signaling pathway

Authors:
- Zhiyong Cai
- Jindi Liu
- Hongliang Bian
- Jinlan Cai
View Affiliations

Affiliations: Newborn Department, Yancheng Maternity and Child Health Care Hospital, Yancheng, Jiangsu 224000, P.R. China
Published online on: August 30, 2016 https://doi.org/10.3892/etm.2016.3629
Pages: 2702-2708

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Astragaloside IV (AS‑IV) is a flavonoid from the plant Astragalus membranaceus (Fisch) Bge that has a wide range of therapeutic effects. The aim of the present study was to examine the effect of AS‑IV on rats with necrotizing enterocolitis (NEC) under oxidative stress and inflammation. Newborn Sprague‑Dawley rats were induced with NEC by asphyxia and hypothermia applied on 3 consecutive days. The rats were orally administered AS‑IV at 25, 50 and 75 mg/kg for 4 days. The results revealed that AS‑IV administration prevented NEC‑induced decrease in the concentration of malondialdehyde and myeloperoxidase, and increase in the activity of glutathione (GSH) and superoxide dismutase in murine models. AS‑IV also inhibited NEC‑induced elevation in the levels of interleukin (IL)‑6, IL‑1β, tumor necrosis factor‑α and nuclear factor (NF)‑κB. The effects of AS‑IV were achieved under inflammation and oxidative stress. Western blotting demonstrated that AS‑IV substantially inhibited the phosphorylated (p)‑IκBα, NF‑κBp65, p‑NF‑κBp65 protein levels and increased vitamin D3 upregulated protein 1 (VDUP1) and IκBα protein levels. These data indicate that AS‑IV may be effective in the protection of NEC‑induced ileum degeneration by inhibiting the levels of inflammatory markers and oxidative stress via the regulation of the VDUP1/NF‑κB signaling pathway.

View Figures

View References

1	Chen CC and Allan WW: Probiotics and the mechanism of necrotizing enterocolitis. Semin Pediatr Surg. 22:94–100. 2013. View Article : Google Scholar : PubMed/NCBI
2	Nanthakumar N, Meng D, Goldstein AM, Zhu W, Lu L, Uauy R, Llanos A, Claud EC and Walker WA: The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: An immature innate immune response. PLoS One. 6:e177762011. View Article : Google Scholar : PubMed/NCBI
3	Schnabl KL, Van Aerde JE, Thomson AB and Clandinin MT: Necrotizing enterocolitis: A multifactorial disease with no cure. World J Gastroenterol. 14:2142–2161. 2008. View Article : Google Scholar : PubMed/NCBI
4	Chandler JC and Hebra A: Necrotizing enterocolitis in infants with very low birth weight. Semin Pediatr Surg. 9:63–72. 2000. View Article : Google Scholar : PubMed/NCBI
5	Chung JW, Jeon JH, Yoon SR and Choi I: Vitamin D3 upregulated protein 1 (VDUP1) is a regulator for redox signaling and stress-mediated diseases. J Dermatol. 33:662–669. 2006. View Article : Google Scholar : PubMed/NCBI
6	Pan CL and Dong ZW: Antiasthmatic effects of eugenol in a mouse model of allergic asthma by regulation of vitamin D3 upregulated protein 1/NF-κB pathway. Inflammation. 38:1385–1393. 2015. View Article : Google Scholar : PubMed/NCBI
7	Kim SY, Suh HY, Chuang JW, Yoon SR and Choi I: Diverse functions of VDUP1 in cell proliferation, differentiation and diseases. Cell Mol Immunol. 4:345–351. 2007.PubMed/NCBI
8	Kutuk O and Basaga H: Inflammation meets oxidation: NF-κB as a mediator of initial lesion development in atherosclerosis. Trends Mol Med. 9:549–557. 2003. View Article : Google Scholar : PubMed/NCBI
9	Tanner SM, Berryhill TF, Ellenburg JL, Jilling T, Cleveland DS, Lorenz RG and Martin CA: Pathogenesis of necrotizing enterocolitis: Modeling the innate immune response. Am J Pathol. 185:4–16. 2015. View Article : Google Scholar : PubMed/NCBI
10	Shilan M and Mohammad A: A review on the role of oxidative stress and inflammation in necrotizing enterocolitis and benefits of the phosphodiesterase inhibitor pentoxifylline. International Journal of Pharmacology. 9:245–250. 2013. View Article : Google Scholar
11	Frost BL, Jilling T and Caplan MS: The importance of pro-inflammatory signaling in neonatal necrotizing enterocolitis. Semin Perinatol. 32:100–106. 2008. View Article : Google Scholar : PubMed/NCBI
12	Cevik M, Karadag CA, Sakiz DE, Tander B and Embleton DD: The role of nitric oxide in an experimental necrotising enterocolitis model. Afr J Paediatr Surg. 10:24–28. 2013. View Article : Google Scholar : PubMed/NCBI
13	He Y, Du M, Gao Y, Liu H, Wang H, Wu X and Wang Z: Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels. PLoS One. 8:e764952013. View Article : Google Scholar : PubMed/NCBI
14	Lai PK, Chan JY, Cheng L, Lau CP, Han SQ, Leung PC, Fung KP and Lau CB: Isolation of anti-inflammatory fractions and compounds from the root of Astragalus membranaceus. Phytother Res. 27:581–587. 2013. View Article : Google Scholar : PubMed/NCBI
15	Ren S, Zhang H, Mu Y, Sun M and Liu P: Pharmacological effects of Astragaloside IV: A literature review. J Tradit Chin Med. 33:413–416. 2013. View Article : Google Scholar : PubMed/NCBI
16	Chen Z, Cai Y, Zhang W, Liu X and Liu S: Astragaloside IV inhibits platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells via the inhibition of p38 MAPK signaling. Exp Ther Med. 8:1253–1258. 2014.PubMed/NCBI
17	Yazıcı S, Akşit H, Korkut O, Sunay B and Çelik T: Effects of boric acid and 2-aminoethoxydiphenyl borate on necrotizing enterocolitis. J Pediatr Gastroenterol Nutr. 58:61–67. 2014. View Article : Google Scholar : PubMed/NCBI
18	Li J, Gu T, Fu X and Zhao R: Effect of salvianolic acid A and C compatibility on inflammatory cytokines in rats with unilateral ureteral obstruction. J Tradit Chin Med. 35:564–570. 2015. View Article : Google Scholar : PubMed/NCBI
19	Nadler EP, Dickinson E, Knisely A, Zhang XR, Boyle P, Beer-Stolz D, Watkins SC and Ford HR: Expression of inducible nitric oxide synthase and interleukin-12 in experimental necrotizing enterocolitis. J Surg Res. 92:71–77. 2000. View Article : Google Scholar : PubMed/NCBI
20	Hillegass LM, Griswold DE, Brickson B and Albrightson-Winslow C: Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods. 24:285–295. 1990. View Article : Google Scholar : PubMed/NCBI
21	Lu HE, Chen Y, Sun XB, Tong B and Fan XH: Effects of luteolin on retinal oxidative stress and inflammation in diabetes. RSC Advances. 5:4898–4904. 2015. View Article : Google Scholar
22	Williams CM and Coleman JW: Induced expression of mRNA for IL-5, IL-6, TNF-alpha, MIP-2 and IFN-gamma in immunologically activated rat peritoneal mast cells: Inhibition by dexamethasone and cyclosporin A. Immunology. 86:244–249. 1995.PubMed/NCBI
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCt method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
24	Lasanianos NG, Kanakaris NK, Dimitriou R, Pape HC and Giannoudis PV: Second hit phenomenon: Existing evidence of clinical implications. Injury. 42:617–629. 2011. View Article : Google Scholar : PubMed/NCBI
25	Qi W, Shen Q, Zhang L, Han LP and Wang S: Study on the inflammatory intervention of erythropoietin on NEC. Exp Ther Med Jun. 11:2221–2224. 2016.
26	Heida FH, Hulscher JB, Schurink M, van Vliet MJ, Kooi EM, Kasper DC, Pones M, Bos AF and Benkoe TM: Bloodstream infections during the onset of necrotizing enterocolitis and their relation with the pro-inflammatory response, gut wall integrity and severity of disease in NEC. J Pediatr Surg. 50:1837–1841. 2015. View Article : Google Scholar : PubMed/NCBI
27	Chung CY, Park YL, Kim N, Oh HH, Myung DS, Kim JS, Cho SB, Lee WS, Kim HS, Ahn BW and Joo YE: Rice prolamin extract ameliorates acute murine colitis by inhibiting nuclear factor-kappaB and modulating intestinal apoptosis and cell proliferation. Clin Exp Immunol. 178:537–547. 2014. View Article : Google Scholar : PubMed/NCBI
28	Everard A, Geurts L, Caesar R, Van Hul M, Matamoros S, Duparc T, Denis RG, Cochez P, Pierard F, Castel J, et al: Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status. Nat Commun. 5:56482014. View Article : Google Scholar : PubMed/NCBI
29	Lu M, Tang F, Zhang J, Luan A, Mei M, Xu C, Zhang S, Wang H and Maslov LN: Astragaloside IV attenuates injury caused by myocardial ischemia/reperfusion in rats via regulation of toll-like receptor 4/nuclear factor-κB signaling pathway. Phytother Res. 29:599–606. 2015. View Article : Google Scholar : PubMed/NCBI