Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched Diets on Mitochondria in Liver Disease

Abstract

Mitochondria play a central role in non-alcoholic fatty liver disease (NAFLD) progression and in the control of cell death signalling during the progression to hepatocellular carcinoma (HCC). Associated with the metabolic syndrome, NAFLD is mostly driven by insulin-resistant white adipose tissue lipolysis that results in an increased hepatic fatty acid influx and the ectopic accumulation of fat in the liver. Upregulation of beta-oxidation as one compensatory mechanism leads to an increase in mitochondrial tricarboxylic acid cycle flux and ATP generation. The progression of NAFLD is associated with alterations in the mitochondrial molecular composition and respiratory capacity, which increases their vulnerability to different stressors, including calcium and pro-inflammatory molecules, which result in an increased generation of reactive oxygen species (ROS) that, altogether, may ultimately lead to mitochondrial dysfunction. This may activate further pro-inflammatory pathways involved in the progression from steatosis to steatohepatitis (NASH). Mushroom-enriched diets, or the administration of their isolated bioactive compounds, have been shown to display beneficial effects on insulin resistance, hepatic steatosis, oxidative stress, and inflammation by regulating nutrient uptake and lipid metabolism as well as modulating the antioxidant activity of the cell. In addition, the gut microbiota has also been described to be modulated by mushroom bioactive molecules, with implications in reducing liver inflammation during NAFLD progression. Dietary mushroom extracts have been reported to have anti-tumorigenic properties and to induce cell-death via the mitochondrial apoptosis pathway. This calls for particular attention to the potential therapeutic properties of these natural compounds which may push the development of novel pharmacological options to treat NASH and HCC. We here review the diverse effects of mushroom-enriched diets in liver disease, emphasizing those effects that are dependent on mitochondria.

<p>Suppression of Cisplatin-Induced Hepatic Injury in Rats Through Alarmin High-Mobility Group Box-1 Pathway by <em>Ganoderma lucidum</em>: Theoretical and Experimental Study</p>

“…This suggestion was aligned with those stated that the cell mediates the activation of either survival or pro-apoptotic pathways, including NF-kB, the tumor suppressor p53 and JNK in response to CP treatment. 72 Furthermore, our results showed that GLM treatment elicited modulation of inflammatory cytokines and suppression of apoptosis in CPinduced hepatotoxicity, which could be due to decreased oxidative stress-mediated apoptosis. This cross-talk between the inflammatory and apoptotic signaling is normalized by administration of GLM in daily-, EOD-and the i.p-treated groups.…”

Characterization of the Nutritional Composition of a Biotechnologically Produced Oyster Mushroom and its Physiological Effects in Obese Zucker Rats

“…[ 72 ] These multitudinous benefits may also be attributed to the abundance of other bioactive molecules that mushrooms harbor, like phenolic compounds, ergosterol, and tocopherols, among others. [ 73 ] Various animal studies have also demonstrated that consumption of mushrooms (fruiting bodies) significantly reduces obesity. [ 74,75 ] It would also be interesting to study whether the biotechnologically produced PSC used in this study may have similar, lipid‐lowering effects in the adipose tissue as seen in the liver of the OPSC group.…”

Soybean fermentation with basidiomycetes (medicinal mushroom mycelia)

“…Many people are interested in edible mushroom fruiting bodies and their mycelia as functional foods because they are less toxic and contain bioactive compounds. Investigators have reported the antitumour [14], antimutagenicity [15], antiviral [16], and antioxidant activities [17] of mushroom fruiting bodies and mycelia. Mushroom mycelia have been investigated for their potential food applications, and they are used to create fermented foods like soybeans, bread, cheese, and alcoholic drinks [18].…”