title: Cyanidin-3-O-β-glucoside inhibits lipopolysaccharide-induced inflammatory response in mouse mastitis model.
abstract: Cyanidin-3-O-β-glucoside (C3G) (CAS number 7084-24-4), a typical anthocyanin pigment that exists in the human diet, has been reported to have anti-inflammatory properties. However, the effect of C3G on lipopolysaccharide (LPS)-induced mastitis and the molecular mechanisms have not been investigated. In this study, we detected the protective effects of C3G on a LPS-induced mouse mastitis model and investigated the molecular mechanisms in LPS-stimulated mouse mammary epithelial cells (MMECs). Our results showed that C3G could attenuate mammary histopathologic changes and myeloperoxidase activity, and inhibit TNF-α, interleukin (IL)-1β, and IL-6 production caused by LPS. Meanwhile, C3G dose-dependently inhibited TNF-α and IL-6 in LPS-stimulated MMECs. C3G suppressed LPS-induced nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) activation. Furthermore, C3G disrupted the formation of lipid rafts by depleting cholesterol. Moreover, C3G activated liver X receptor (LXR)-ABCG1-dependent cholesterol efflux. Knockdown of LXRα abrogated the anti-inflammatory effects of C3G. In conclusion, C3G has a protective effect on LPS-induced mastitis. The promising anti-inflammatory mechanisms of C3G are associated with upregulation of the LXRα-ABCG1 pathway which result in disrupting lipid rafts by depleting cholesterol, thereby suppressing toll-like receptor 4-mediated NF-κB and IRF3 signaling pathways induced by LPS.
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Zhengkai
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Ershun
authors.initials: E
authors.lastname: Zhou
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Naisheng
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology; D008413:Mastitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice
chemical_list: D000872:Anthocyanins; D016207:Cytokines; D005960:Glucosides; D008070:Lipopolysaccharides; C462279:cyanidin-3-O-beta-glucopyranoside
keywords: ATP binding cassette transporter G1; interferon regulatory factor 3; lipid raft; liver X receptor; nuclear factor-κB; toll-like receptor 4
references.citation: Eur J Pharmacol. 2013 Apr 5;705(1-3):79-85
references.pmid: 23499696
references.citation: J Mammary Gland Biol Neoplasia. 2002 Apr;7(2):135-46
references.pmid: 12463736
references.citation: J Lipid Res. 2010 Feb;51(2):334-44
references.pmid: 19648651
references.citation: Vet Microbiol. 2009 Feb 16;134(1-2):82-8
references.pmid: 18930610
references.citation: J Lipid Res. 2010 Nov;51(11):3196-206
references.pmid: 20650929
references.citation: Domest Anim Endocrinol. 2004 Mar;26(2):111-26
references.pmid: 14757184
references.citation: Cell Metab. 2005 Feb;1(2):121-31
references.pmid: 16054053
references.citation: Life Sci. 2008 Aug 1;83(5-6):176-84
references.pmid: 18619979
references.citation: Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):266-71
references.pmid: 9874807
references.citation: Physiol Res. 2004;53(3):235-43
references.pmid: 15209530
references.citation: Br J Pharmacol. 2010 Dec;161(7):1628-44
references.pmid: 20726986
references.citation: J Clin Invest. 2006 Mar;116(3):607-14
references.pmid: 16511593
references.citation: Mol Immunol. 2008 Apr;45(7):2007-16
references.pmid: 18061674
references.citation: J Nutr. 2012 Jun;142(6):1033-7
references.pmid: 22535762
references.citation: J Exp Med. 2003 Oct 6;198(7):1043-55
references.pmid: 14517278
references.citation: J Lipid Res. 2004 Nov;45(11):2052-62
references.pmid: 15292368
references.citation: Infect Immun. 2006 Mar;74(3):1907-15
references.pmid: 16495566
references.citation: Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):534-40
references.pmid: 16357317
references.citation: Mol Nutr Food Res. 2012 Apr;56(4):610-21
references.pmid: 22495986
references.citation: J Biol Chem. 2008 Aug 22;283(34):22930-41
references.pmid: 18552351
references.citation: Vet Res. 2013 Jun 11;44:40
references.pmid: 23758654
references.citation: J Immunol. 2007 Feb 1;178(3):1243-9
references.pmid: 17237368
references.citation: Cytokine. 2005 Jul 7;31(1):72-86
references.pmid: 15882946
references.citation: Arterioscler Thromb Vasc Biol. 2006 Jun;26(6):1310-6
references.pmid: 16556852
references.citation: Nat Med. 2003 Feb;9(2):213-9
references.pmid: 12524534
references.citation: J Cell Sci. 2002 Jun 15;115(Pt 12):2603-11
references.pmid: 12045230
references.citation: J Exp Med. 2006 Oct 2;203(10):2377-89
references.pmid: 17000866
references.citation: J Immunol. 1999 Apr 1;162(7):3749-52
references.pmid: 10201887
references.citation: Mol Immunol. 2006 Feb;43(6):607-12
references.pmid: 15904959
references.citation: Inflamm Res. 2010 Sep;59(9):723-30
references.pmid: 20309718
references.citation: Contraception. 1984 Dec;30(6):505-22
references.pmid: 6241559
references.citation: FASEB J. 2004 Jul;18(10):1080-9
references.pmid: 15226268