Bioactive Compounds from the Mushroom-Forming Fungus Chlorophyllum molybdites.

A novel compound (1) along with two known compounds (2 and 3) were isolated from the culture broth of Chlorophyllum molybdites, and three known compounds (4-6) were isolated from its fruiting bodies. The planar structure of 1 was determined by the interpretation of spectroscopic data. By comparing the specific rotation of the compound with that of the analog compound, the absolute configuration of 1 was determined to be R. This is the first time that compounds 2-4 were isolated from a mushroom-forming fungus. Compound 2 showed significant inhibition activity against Axl and immune checkpoints (PD-L1, PD-L2). In the bioassay to examine growth inhibitory activity against the phytopathogenic bacteria Peptobacterium carotovorum, Clavibacter michiganensis and Burkholderia glumae, compounds 2 and 3 inhibited the growth of P. carotovorum and C. michiganensis. In the bioassay to examine plant growth regulatory activity, compounds 1-4 showed a significant regulatory activity on lettuce growth.

Utilization of Corn Steep Liquor for the Production of Fairy Chemicals by Lepista sordida Mycelia.

There are various potential practical uses of fairy chemicals (FCs) in the fields of agriculture, cosmetics, and medicine; however, the production costs of FCs are very high. To enable the practical use of FCs, more efficient and inexpensive methods of culturing the mycelia of FCs-producing fungi and producing FCs need to be developed. The purpose of the present study was to determine methods of reducing the production costs of FCs and mycelia of the FCs-producing fungus Lepista sordida. We investigated the effects of four food industrial by-products, i.e., corn steep liquor (CSL), rice bran, wheat bran, and Japanese liquor lees, as nutritional additives in the liquid culture medium of the fungus. We found that CSL was more effective than the other tested additives in increasing the production of FCs and mycelia. Medium containing 1% CSL was optimal for increasing the mycelial yield while medium containing 6% CSL was optimal for increasing the production of FCs. The reason for this difference in the optimal CSL concentration was considered to be related to the stress on the mycelia caused by the amount of nutrients in the liquid medium. These results are expected to facilitate the practical use of FCs and the mycelia of FCs-producing fungi.

Anti-phytopathogenic-bacterial fatty acids from the mycelia of the edible mushroom Agaricus blazei.

Five compounds including a new compound (1) were isolated from mycelia of a mushroom-forming fungus Agaricus blazei. Compound 2 was isolated from nature for the first time. Their structures were determined by the interpretation of spectroscopic data. In the bioassay examining growth inhibitory activity against phytopathogenic bacteria Clavibacter michiganensis, Burkholderia glumae, and Peptobacterium carotovorum, all the compounds showed inhibition effects on C. michiganensis. Compounds 3 and 4 also showed weak inhibitory activity against growth of B. glumae.

A new lanostane triterpenoid from the mushroom Hypholoma fasciculare.

A novel compound (1) and 3 known compounds (2-4) were isolated from the fruiting bodies of Hypholoma fasciculare. The structure of 1 was determined by the interpretation of spectroscopic data. Compounds 2-4 were identified by comparing the spectra data of known compounds. In the bioassay examining growth inhibitory activity against phytopathogenic bacteria Clavibacter michiganensis, Burkholderia glumae, and Peptobacterium carotovorum, compounds 1, 2, and 4 showed inhibition effects on C. michiganensis only.

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

The leading cause of death worldwide is cancer. Many reports have proved the beneficial effect of mushrooms in cancer. However, the precise mechanism is not completely clear. In the present study, we focused on the medicinal properties of biomolecules released by fairy ring-forming mushrooms. Fairy chemicals generally stimulate or inhibit the growth of surrounding vegetation. In the present study, we evaluated whether fairy chemicals (2-azahypoxanthine, 2-aza-8-oxohypoxanthine, and imidazole-4-carboxamide) exert anticancer activity by decreasing the expression of Axl and immune checkpoint molecules in melanoma cells. We used B16F10 melanoma cell lines and a melanoma xenograft model in the experiments. Treatment of melanoma xenograft with cisplatin combined with imidazole-4-carboxamide significantly decreased the tumor volume compared to untreated mice or mice treated cisplatin alone. In addition, mice treated with cisplatin and imidazole-4-carboxamide showed increased peritumoral infiltration of T cells compared to mice treated with cisplatin alone. In vitro studies showed that all fairy chemicals, including imidazole-4-carboxamide, inhibit the expression of immune checkpoint molecules and Axl compared to controls. Imidazole-4-carboxamide also significantly blocks the cisplatin-induced upregulation of PD-L1. These observations point to the fairy chemical imidazole-4-carboxamide as a promising coadjuvant therapy with cisplatin in patients with cancer.

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

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.

Gram-Scale, Stereoselective Synthesis and Biological Evaluation of (+)-Armillariol C.

Natural products with heteroaromatic cores are ample and widespread in nature, with many compounds exhibiting promising therapeutic properties. (+)-Armillariol C (1a) is a furan-based natural product isolated from Armillaria species. Herein, we report the first enantioselective synthesis of (+)-armillariol C (1a, 79% overall yield), its enantiomer (1b), and four other analogues, on a gram-scale, using microwave-mediated, Suzuki-Miyaura cross-coupling and Sharpless asymmetric dihydroxylation reactions. Compounds were tested for plant- and mycelia-growth regulatory activity, with 1b, 7a, and 7b showing the strongest inhibitory properties in a lettuce assay and 7b and 9b inhibiting Flammulina velutipes.

Plant growth regulators from the fruiting bodies of Tricholoma flavovirens.

A novel indole derivative (1) and three known compounds (2-4) were isolated from the fruiting bodies of Tricholoma flavovirens. Their structures were determined or identified by the interpretation of spectroscopic data. Compounds 1 and 2 promoted root growth of lettuce and inhibited hypocotyl growth at 1 µmol/paper. Compound 3 inhibited hypocotyl and root growth at 100 nmol/paper.

Bioactive sesquiterpene aryl esters from the culture broth of Armillaria sp.

Two new compounds, 10-dehydroxymelleolide D (1) and 13-hydroxymelleolide K (2), along with seven known compounds, 5'-O-methylmelledonal (3), melleolide D (4), 13-hydroxydihydromelleolide (5), melleolide (6), armillarinin (7), armillaridin (8), and armillarikin (9), were isolated from the culture broth of Armillaria sp. Their structures were determined by spectroscopic data analysis. All the compounds inhibited plant growth of lettuce. Melleolide (6) and armillarikin (9) inhibited mycelial growth of Coprinopsis cinerea and/or Flammulina velutipes.

A new compound from the mushroom Tricholoma flavovirens.

A novel compound (1) and a known one (2) were isolated from the fruiting bodies of Tricholoma flavovirens. Their structures were determined by the interpretation of spectroscopic data. Both compounds showed inhibition effects on the growth of hypocotyl of lettuce with significant differences. In addition, compound 1 showed a promotion effect on the growth of root with significant differences and 2 had the similar tendency to promote the growth.

Anti-aging and anti-microbial effects of melleolide on various types of yeast.

The chronological lifespan (CLS) of the budding yeast Saccharomyces cerevisiae is a model for the aging of post-mitotic cells in higher eukaryotes. In this study, we found that the sesquiterpene aryl ester melleolide expands the CLS of budding yeast. In contrast, melleolide compromised the CLS of the fission yeast Schizosaccharomyces pombe. This indicates that melleolide might have a potential anti-aging activity against some types of cell, and that it might be useful as a selective anti-fungal drug.

Isolation of bioactive steroids from the Stropharia rugosoannulata mushroom and absolute configuration of strophasterol B.

The absolute configuration of strophasterol B (1) isolated from the fruiting bodies of Stropharia rugosoannulata was determined by an X-ray crystallographic analysis. Three compounds (2 to 4) were isolated from the mushroom which suppressed or promoted lettuce growth.