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Pretreatment with dihydroquercetin, a dietary flavonoid, protected against concanavalin A-induced immunological hepatic injury in mice and TNF-α/ActD-induced apoptosis in HepG2 cells

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Abstract

We have previously demonstrated the hepatoprotective effect of dihydroquercetin (DHQ) against concanavalin A (Con A)-induced immunological hepatic injury in mice. In this study, we investigated the immunoregulatory effects of DHQ on Con A-induced liver injury in mice. DHQ administration significantly decreased the serum levels of alanine transaminase and aspartate transaminase, effectively prevented liver damage, and increased the survival rate of Con A-treated mice. Immunohistochemistry examination revealed that supplementation with DHQ obviously reduced infiltration of CD4+ and CD8+ T cells in the injured liver tissues. Furthermore, DHQ administration resulted in down-regulation of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-4, and IL-10), the chemokine osteopontin, apoptosis factors (Fas and FasL), transcription factors that regulate Th cell differentiation (T-bet and GATA-3), perforin, granzyme B, and inducible nitric oxide synthase (iNOS). In vitro, treatment with DHQ protected HepG2 cells against TNF-α/ActD-induced apoptosis by inhibiting the activation of caspase-3, caspase-7, and caspase-8. In addition, DHQ reduced phosphorylation of NF-kB/p65, and inhibited the expressions of pro-apoptotic factors (p53 and Bax), while it up-regulated the expression of the anti-apoptotic factor Bcl-2. Our findings suggest that the immunosuppressive effects of DHQ ameliorated Con A-mediated immunological liver injury by reducing the expression of pro-inflammatory mediators and infiltration of CD4+ and CD8+ T cells in liver tissues, and DHQ protected HepG2 cells against TNF-α/ActD-induced apoptosis possibly via modulation of the caspase and NF-kB pathways.

Graphical abstract: Pretreatment with dihydroquercetin, a dietary flavonoid, protected against concanavalin A-induced immunological hepatic injury in mice and TNF-α/ActD-induced apoptosis in HepG2 cells

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Publication details

The article was received on 18 Jul 2017, accepted on 13 Feb 2018 and first published on 06 Mar 2018


Article type: Paper
DOI: 10.1039/C7FO01073G
Citation: Food Funct., 2018, Advance Article
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    Pretreatment with dihydroquercetin, a dietary flavonoid, protected against concanavalin A-induced immunological hepatic injury in mice and TNF-α/ActD-induced apoptosis in HepG2 cells

    J. Chen, X. Sun, T. Xia, Q. Mao and L. Zhong, Food Funct., 2018, Advance Article , DOI: 10.1039/C7FO01073G

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