White Button Mushroom Extracts Modulate Hepatic Fibrosis Progression, Inflammation, and Oxidative Stress In Vitro and in LDLR-/- Mice.

Paloma Gallego,Amparo Luque-Sierra,José A Del Campo,Franz Martín,Juan D Bautista,Pilar Carbonero,Lourdes Grande,Gonzalo Falcon

doi:10.3390/foods10081788

Abstract

Liver fibrosis can be caused by non-alcoholic steatohepatitis (NASH), among other conditions. We performed a study to analyze the effects of a nontoxic, water-soluble extract of the edible mushroom Agaricus bisporus (AB) as a potential inhibitor of fibrosis progression in vitro using human hepatic stellate cell (LX2) cultures and in vivo in LDLR-/- mice. Treatment of LX2 cells with the AB extract reduced the levels of fibrotic and oxidative-related markers and increased the levels of GATA4 expression. In LDLR-/- mice with high-fat diet (HFD)-induced liver fibrosis and inflammation, the progression of fibrosis, oxidative stress, inflammation, and apoptosis were prevented by AB extract treatment. Moreover, in the mouse model, AB extract could exert an antiatherogenic effect. These data suggest that AB mushroom extract seems to exert protective effects by alleviating inflammation and oxidative stress during the progression of liver fibrosis, possibly due to a decrease in Toll-like receptor 4 (TLR4) expression and a reduction in Nod-like receptor protein 3 (NLRP3) inflammasome activation. In addition, we observed a potential atheroprotective effect in our mouse model.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is defined as the accumulation of fat in hepatocytes in the absence of excessive alcohol intake [1,2]
TPM2β and COL1α1 gene expression levels were reduced when LX2 cells were treated with 0.2 mg/mL Agaricus bisporus (AB) extract (p ≤ 0.01, Figure 1b; p ≤ 0.001, Figure 1c, respectively), while no significant differences were found in response to 1 mg/mL compared to those in control cells
The gene expression level of glutathione peroxidase 3 (GPX3) was significantly increased in HFD45 (p ≤ 0.01, d = 1.422, β err = 0.493; Figure 5f), while AB-treatment induced a significant reduction with a large effect size compared to HFD45 (p ≤ 0.01, d = 1.716, β err = 0.393o7f )1.9 we observed significant increases in Toll-like receptor 4 (TLR4) levels in the HFD45 group (p ≤ 0.05, d = 3.485, β err = 0.116) compared with the control LFD group

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is defined as the accumulation of fat in hepatocytes in the absence of excessive alcohol intake [1,2]. Several families of pattern-recognition receptors (PRRs) recognize highly conserved pathogen-associated molecular patterns and host-derived damage-associated molecular patterns (DAMPs), and once activated, these receptors induce signaling cascades that lead to the induction of proinflammatory cytokines. Among these families are Toll-like receptors (TLRs) and Nod-like receptors (NLRs) [7,8]. Saturated fatty acids (SFAs) can promote the development and progression of several noninfectious and inflammatory diseases, such as NAFLD, atherosclerosis, insulin resistance, and obesity, by activating Toll-like receptor 4 (TLR4) signaling in rodent models, promoting the inflammatory aspects of metabolic syndrome [7,9]

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