Structure-Based Virtual Screening of Sterols and Triterpenoids Isolated from Ganoderma (Agaricomycetes) Medicinal Mushrooms Shows Differences in Their Affinity for Human Glucocorticoid and Mineralocorticoid Receptors.

An extensive database of sterols and triterpenoids isolated from Ganoderma mushrooms was evaluated by in silico structure-based virtual screening to determine their respective ligand affinities for the glucocorticoid or mineralocorticoid receptor (GCR or MNR). The main ligands for GCR in our database were ergosta-7,22-dien-3-one (compound 1) and ganodermaside B (compound 2), while the best ligands for MNR were 2ß,3α,9α-trihydroxyergosta-7,22-diene (compound 8) and 5α-ergosta-7,22-dien-3ß-ol (compound 3). The binding free energy (BFE) values calculated for such metabolites were similar to those of the natural ligands for each receptor (i.e., dexamethasone for GCR and aldosterone for MNR). Moreover, the differences between mean BFE values calculated for both receptors suggest that ergosta-7,22-dien-3-one (compound 1), ganodermaside B (compound 2), fungisterol (compound 5), ganoderic acid Ma (compound 9), and cerevisterol (compound 10) might be used as specific ligands for GCR, with a significantly lower affinity for MNR. Finally, it is worth noting that even though this work is exclusively theoretical, the reported bioactivities (either pro- or anti-inflammatory) for those metabolites that were previously studied are consistent with our findings, suggesting that the well-known immunomodulatory effect of Ganoderma triterpenoids and sterols might be attributed, at least partially, to their ability to act as specific GCR ligands.

In Vitro Expression of Toll-Like Receptors and Proinflammatory Molecules Induced by Ergosta- 7,22-Dien-3-One Isolated from a Wild Mexican Strain of Ganoderma oerstedii (Agaricomycetes).

Compounds showing pharmacological activity on the immune system are of interest because of their therapeutic potential in the treatment of many diseases. However, data from primary human immune cells and in vivo studies are limited. The aim of this study was to analyze the ability to induce the expression of Toll-like receptors (TLRs) and proinflammatory molecules on cells involved in the immune system using the compound ergosta-7,22-dien-3- one, isolated from a wild Mexican strain of Ganoderma oerstedii. According to our study, ergosta-7,22-dien-3-one did not present any cytotoxic effect on HeLa or J774A.1 cells, and it was able to stimulate nitric oxide production, induce the expression of genes, and induce the production of TLRs, cytokines, chemokines, and cellular adhesion molecules in J774A.1 cells, based on reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Here we report a new pro-inflammatory property of ergosta-7,22-dien-3-one, which should be considered as a possible adjuvant property in view of its biological activity.

Cytotoxic activity and induction of inflammatory mediators of the methanol:chloroform extract of Fusarium moniliforme / Actividad citotóxica e inducción de mediadores inflamatorios del extracto metanol: cloroformo de Fusarium moniliforme

Background. Fusarium moniliforme is a phytopathogenic facultative fungus with a cosmopolitan distribution in all types of climates, and has a wide host range, including, among others, bean, rice, wheat and sorghum crops. There is a current lack of knowledge regarding the potential of these fungi, so it is considered to be of great importance to obtain information related to the biological activity of extracts and secondary metabolites. Aims. An evaluation of the role of methanol:chloroform extract of F. moniliforme in the production of inflammatory cytokines and their cytotoxic activity. Methods. The production of nitric oxide was analyzed by the Griess method, the production of cytokines using ELISA, and the effects of the extract on cell cycle and induction of apoptosis by flow cytometry. Results. The extract of F. moniliforme was seen to be able to stimulate nitric oxide (NO) production in J774A.1 cells, as well as to produce cytokines such as, IL-1β, IL-6, and TNF-α. It was also observed that the extract of F. moniliforme produces activity on cell cycle modulation and apoptosis when tested in carcinogenic cell lines. Conclusions. The results obtained from this study open the possibility of obtaining and identifying metabolites of the extract of F. moniliforme that can be evaluated for possible use in cancer therapy (AU)

Antecedentes. Fusarium moniliforme es un hongo fitopatógeno facultativo con distribución cosmopolita en todos los tipos de climas y con una gran variedad de huéspedes, como el frijol, el arroz, el trigo y el sorgo. Actualmente existe una falta de conocimiento sobre el potencial de este hongo, por lo que es de gran importancia obtener información relacionada con la actividad biológica de los extractos y sus metabolitos secundarios. Objetivos. En este trabajo se evaluó el papel del extracto metanol:cloroformo de F. moniliforme sobre la producción de citocinas y su actividad citotóxica sobre líneas celulares. Métodos. Se analizó la producción de óxido nítrico por el método de Griess, la producción de citocinas se evalúo por el método de ELISA y los efectos del extracto sobre el ciclo celular e inducción de apoptosis se analizó por citometría de flujo. Resultados. El extracto de F. moniliforme fue capaz de inducir la producción de óxido nítrico (ON) en células J774A.1, así como la producción de citocinas IL-1β, IL-6 y TNF-α. También se observó que el extracto de F. moniliforme posee actividad en la modulación del ciclo celular y en la inducción de apoptosis observada en líneas células cancerígenas. Conclusiones. Los resultados de este trabajo abren la posibilidad de obtener e identificar los metabolitos del extracto de F. moniliforme para que puedan ser evaluados en una posible terapia para el cáncer (AU)

Cytotoxic activity and induction of inflammatory mediators of the methanol:chloroform extract of Fusarium moniliforme.

BACKGROUND: Fusarium moniliforme is a phytopathogenic facultative fungus with a cosmopolitan distribution in all types of climates, and has a wide host range, including, among others, bean, rice, wheat and sorghum crops. There is a current lack of knowledge regarding the potential of these fungi, so it is considered to be of great importance to obtain information related to the biological activity of extracts and secondary metabolites. AIMS: An evaluation of the role of methanol:chloroform extract of F. moniliforme in the production of inflammatory cytokines and their cytotoxic activity. METHODS: The production of nitric oxide was analyzed by the Griess method, the production of cytokines using ELISA, and the effects of the extract on cell cycle and induction of apoptosis by flow cytometry. RESULTS: The extract of F. moniliforme was seen to be able to stimulate nitric oxide (NO) production in J774A.1 cells, as well as to produce cytokines such as, IL-1ß, IL-6, and TNF-α. It was also observed that the extract of F. moniliforme produces activity on cell cycle modulation and apoptosis when tested in carcinogenic cell lines. CONCLUSIONS: The results obtained from this study open the possibility of obtaining and identifying metabolites of the extract of F. moniliforme that can be evaluated for possible use in cancer therapy.