Subcritical Water Extracts from Agaricus blazei Murrill’s Mycelium Inhibit the Expression of Immune Checkpoint Molecules and Axl Receptor

Abstract

Agaricus blazei Murrill or Himematsutake is an edible and medicinal mushroom. Agaricus blazei Murrill’s fruiting body extracts have anticancer properties, although the mechanism is unknown. Basic or organic solvents, which are hazardous for human health, are generally used to prepare Agaricus blazei Murrill’s extracts. The inhibition of immune checkpoint molecules and Axl receptor is an effective therapy in cancer. This study assessed whether subcritical water extracts of the Agaricus blazei Murrill’s fruiting body or mycelium affect the expression of Axl and immune checkpoint molecules in lung cancer cells. We used A549 cells and mouse bone marrow-derived dendritic cells in the experiments. We prepared subcritical water extracts from the Agaricus blazei Murrill’s fruiting body or mycelium. The subcritical water extracts from the Agaricus blazei Murrill’s fruiting body or mycelium significantly inhibited the expression of immune checkpoint molecules and Axl compared to saline-treated cells. Additionally, the hot water extract, subcritical water extract, and the hot water extraction residue subcritical water extract from the Agaricus blazei Murrill’s mycelium significantly enhanced the expression of maturation markers in dendritic cells. These observations suggest that the subcritical water extract from Agaricus blazei Murrill’s mycelium is a promising therapeutic tool for stimulating the immune response in cancer.

The Fairy Chemical Imidazole-4-carboxamide Inhibits the Expression of Axl, PD-L1, and PD-L2 and Improves Response to Cisplatin in Melanoma

“…AOH significantly reduced the relative mRNA expression of Axl, but not that of PD-L1 or PD-L2 in B16F10 cells (Figure 4A). Mushroom's extracts have been shown to inhibit the expression of Axl and immune checkpoint molecules in the lung adenocarcinoma A549 cell lines [25]. Therefore, to validate our findings, we evaluated whether the fairy chemicals can also inhibit the expression of Axl, PD-L1, and PD-L2 in A549 cells.…”

“…Supplementary Table S1 described the source of antibodies. Cells cultured similarly in the presence of an equal amount of saline (SAL) were the negative controls, and cells stimulated with the fruiting body alkaline extract from Agaricus blazei Murrill were the positive controls [25].…”

“…Previous studies suggested that fruiting body extracts from mushrooms, including Leucopaxillus giganteus, and Pleurocybella porrigens may stimulate host immunity by suppressing the expression of Axl, PD-L1, and PD-L2 in the non-small cell lung cancer cell lines A549 and H3255 cells [23,24]. Apart from decreasing the expression of Axl and immune checkpoint molecules in the non-small cell lung cancer cell lines A549, the subcritical water extracts of Agaricus blazei Murril's mycelium also stimulate the maturation of dendritic cells [25]. In the present study, we focused on the medicinal properties of fairy chemicals produced by mushrooms that form fairy rings.…”

Valorization of mushroom by‐products: a review

“…used ethanol as a solvent to obtain triterpenoids from the by‐product after hot water extraction of Ganoderma lucidum 40 . Agaricus blazei residues generated after alcohol extraction contained rich phenolic compounds including flavonoids 41 . Extracts from mushroom ergosterol have been suggested to have the effect of lowering cholesterol absorption and synthesis 42 .…”

“…40 Agaricus blazei residues generated after alcohol extraction contained rich phenolic compounds including flavonoids. 41 Extracts from mushroom ergosterol have been suggested to have the effect of lowering cholesterol absorption and synthesis. 42 Ultrasonic-assisted treatment might also increase the extraction of ⊍-glucan from the MR. 43 These by-products have high moisture content and require effective drying methods for preservation purposes.…”