Extract Attenuates Inflammation and Oxidative Stress in Intestinal Epithelial Cells Via NF-κB Activation and Nrf2 Response

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Mar 15

PMID 29534459

Citations 54

Authors

Simona Adesso

Rosario Russo

Andrea Quaroni

Giuseppina Autore

Stefania Marzocco

Affiliations

Soon will be listed here.

Abstract

, dried root extract, also known as , is used in traditional Chinese medicine as a tonic remedy. Moreover, it has been reported that could attenuate intestinal inflammation; however, the underlying mechanism for its anti-inflammatory activity in intestinal epithelial cells (IECs) remains unclear. In this study, we evaluated extract (5-100 µg/mL) in a model of inflammation and oxidative stress for IECs. We showed that extract reduced the inflammatory response induced by lipopolysaccharide from (LPS) plus interferon-γ (IFN), decreasing tumor necrosis factor-α (TNF-α) release, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, nitrotyrosine formation, nuclear factor-κB (NF-κB) activation, and reactive oxygen species (ROS) release in the non-tumorigenic intestinal epithelial cell line (IEC-6). The antioxidant potential of extract was also evaluated in a model of hydrogen peroxide (H₂O₂)-induced oxidative stress in IEC-6, indicating that this extract reduced ROS release and increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation and the expression of antioxidant cytoprotective factors in these cells. The results contributed to clarify the mechanisms involved in extract-reduced inflammation and highlighted the potential use of this extract as an anti-inflammatory and antioxidant remedy for intestinal diseases.

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References

Huang B, Chandra S, Shih D . Skin manifestations of inflammatory bowel disease. Front Physiol. 2012; 3:13. PMC: 3273725. DOI: 10.3389/fphys.2012.00013. View

Valentine J, Tannahill C, Stevenot S, Sallustio J, Nick H, Eaker E . Colitis and interleukin 1beta up-regulate inducible nitric oxide synthase and superoxide dismutase in rat myenteric neurons. Gastroenterology. 1996; 111(1):56-64. DOI: 10.1053/gast.1996.v111.pm8698225. View

Adesso S, Autore G, Quaroni A, Popolo A, Severino L, Marzocco S . The Food Contaminants Nivalenol and Deoxynivalenol Induce Inflammation in Intestinal Epithelial Cells by Regulating Reactive Oxygen Species Release. Nutrients. 2017; 9(12). PMC: 5748793. DOI: 10.3390/nu9121343. View

Matricon J, Barnich N, Ardid D . Immunopathogenesis of inflammatory bowel disease. Self Nonself. 2011; 1(4):299-309. PMC: 3062384. DOI: 10.4161/self.1.4.13560. View

Shao B, Xu W, Dai H, Tu P, Li Z, Gao X . A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb. Biochem Biophys Res Commun. 2004; 320(4):1103-11. DOI: 10.1016/j.bbrc.2004.06.065. View

Luo K, Cao S . Endoplasmic reticulum stress in intestinal epithelial cell function and inflammatory bowel disease. Gastroenterol Res Pract. 2015; 2015:328791. PMC: 4338396. DOI: 10.1155/2015/328791. View

Li C, Li L, Lou J, Yang W, Lei T, Li Y . The protective effects of traditional Chinese medicine prescription, han-dan-gan-le, on CCl4-induced liver fibrosis in rats. Am J Chin Med. 1998; 26(3-4):325-32. DOI: 10.1142/S0192415X98000361. View

Di Cesare Mannelli L, Zanardelli M, Bartolucci G, Karioti A, Bilia A, Vannacci A . In Vitro Evidence for the Use of Astragali Radix Extracts as Adjuvant against Oxaliplatin-Induced Neurotoxicity. Planta Med. 2015; 81(12-13):1045-55. DOI: 10.1055/s-0035-1546117. View

Gunther C, Neumann H, Neurath M, Becker C . Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium. Gut. 2012; 62(7):1062-71. DOI: 10.1136/gutjnl-2011-301364. View

10.

Hei Z, Huang H, Zhang J, Chen B, Li X . Protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury after hemorrhagic shock in rats. World J Gastroenterol. 2005; 11(32):4986-91. PMC: 4321914. DOI: 10.3748/wjg.v11.i32.4986. View

11.

Law P, Auyeung K, Chan L, Ko J . Astragalus saponins downregulate vascular endothelial growth factor under cobalt chloride-stimulated hypoxia in colon cancer cells. BMC Complement Altern Med. 2012; 12:160. PMC: 3493357. DOI: 10.1186/1472-6882-12-160. View

12.

Gao X, Xu X, Pan R, Li Y, Luo Y, Xia Y . Saponin fraction from Astragalus membranaceus roots protects mice against polymicrobial sepsis induced by cecal ligation and puncture by inhibiting inflammation and upregulating protein C pathway. J Nat Med. 2009; 63(4):421-9. DOI: 10.1007/s11418-009-0348-2. View

13.

Lv J, Zhang Y, Tian Z, Liu F, Shi Y, Liu Y . Astragalus polysaccharides protect against dextran sulfate sodium-induced colitis by inhibiting NF-κВ activation. Int J Biol Macromol. 2017; 98:723-729. DOI: 10.1016/j.ijbiomac.2017.02.024. View

14.

Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe S . Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014; 94(2):329-54. PMC: 4044300. DOI: 10.1152/physrev.00040.2012. View

15.

Marzocco S, Calabrone L, Adesso S, Larocca M, Franceschelli S, Autore G . Anti-inflammatory activity of horseradish (Armoracia rusticana) root extracts in LPS-stimulated macrophages. Food Funct. 2015; 6(12):3778-88. DOI: 10.1039/c5fo00475f. View

16.

You H, Lu Y, Gui D, Peng A, Chen J, Gu Y . Aqueous extract of Astragali Radix ameliorates proteinuria in adriamycin nephropathy rats through inhibition of oxidative stress and endothelial nitric oxide synthase. J Ethnopharmacol. 2010; 134(1):176-82. DOI: 10.1016/j.jep.2010.11.064. View

17.

Li L, Hou X, Xu R, Liu C, Tu M . Research review on the pharmacological effects of astragaloside IV. Fundam Clin Pharmacol. 2016; 31(1):17-36. DOI: 10.1111/fcp.12232. View

18.

Kim C, Ha H, Kim J, Kim Y, Kwon S, Park S . Induction of growth hormone by the roots of Astragalus membranaceus in pituitary cell culture. Arch Pharm Res. 2003; 26(1):34-9. DOI: 10.1007/BF03179928. View

19.

Wang Y, Wang H, Qian C, Tang J, Zhou W, Liu X . 3-(2-Oxo-2-phenylethylidene)-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-one (compound 1), a novel potent Nrf2/ARE inducer, protects against DSS-induced colitis via inhibiting NLRP3 inflammasome. Biochem Pharmacol. 2015; 101:71-86. DOI: 10.1016/j.bcp.2015.11.015. View

20.

Lee Y, Han O, Park C, Yang C, Jeon T, Yoo W . Pro-inflammatory cytokine gene expression and nitric oxide regulation of aqueous extracted Astragali radix in RAW 264.7 macrophage cells. J Ethnopharmacol. 2005; 100(3):289-94. DOI: 10.1016/j.jep.2005.03.009. View