Dataset Information

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

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.

SUBMITTER: Gallego P

PROVIDER: S-EPMC8392037 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Gallego Paloma P Luque-Sierra Amparo A Falcon Gonzalo G Carbonero Pilar P Grande Lourdes L Bautista Juan D JD Martín Franz F Del Campo José A JA

Foods (Basel, Switzerland) 20210801 8

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 ...[more]

PMID: 34441565

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Project description:BackgroundIn a previously reported Phase I trial, we observed therapy-associated declines in circulating myeloid-derived suppressor cells (MDSCs) with the administration of white button mushroom (WBM) tablets in prostate cancer (PCa) patients. These observations led us to hypothesise that WBM could mitigate PCa progression by suppressing MDSCs.MethodsWe performed bidirectional translational research to examine the immunomodulatory effects of WBM consumption in both syngeneic murine PCa models and patients with PCa participating in an ongoing randomised Phase II trial (NCT04519879).ResultsIn murine models, WBM treatment significantly suppressed tumour growth with a reduction in both the number and function of MDSCs, which in turn promoted antitumour immune responses mediated by T cells and natural killer (NK) cells. In patients, after consumption of WBM tablets for 3 months, we observed a decline in circulating polymorphonuclear MDSCs (PMN-MDSCs), along with an increase in cytotoxic CD8+ T and NK cells. Furthermore, single immune cell profiling of peripheral blood from WBM-treated patients showed suppressed STAT3/IRF1 and TGFβ signalling in circulating PMN-MDSCs. Subclusters of PMN-MDSCs presented transcriptional profiles associated with responsiveness to fungi, neutrophil chemotaxis, leukocyte aggregation, and regulation of inflammatory response. Finally, in mouse models of PCa, we found that WBM consumption enhanced the anticancer activity of anti-PD-1 antibodies, indicating that WBM may be used as an adjuvant therapy with immune checkpoint inhibitors.ConclusionOur results from PCa murine models and patients provide mechanistic insights into the immunomodulatory effects of WBM and provide a scientific foundation for WBM as a nutraceutical intervention to delay or prevent PCa progression.HighlightsWhite button mushroom (WBM) treatment resulted in a reduction in pro-tumoural MDSCs, notably polymorphonuclear MDSCs (PMN-MDSCs), along with activation of anti-tumoural T and NK cells. Human single immune cell gene expression profiling shed light on the molecular alterations induced by WBM, specifically on PMN-MDSCs. A proof-of-concept study combining WBM with PD-1 blockade in murine models revealed an additive effect on tumour regression and survival outcomes, highlighting the clinical relevance of WBM in cancer management.

Dataset Information

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

Publications

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

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