ABSTRACT
A common edible mushroom Lentinula edodes, is an important source of numerous biologically active substances, including polysaccharides, with immunomodulatory and antitumor properties. In the present work, the biological activity of the crude, homogenous (Se)-enriched fraction (named Se-Le-30), which has been isolated from L. edodes mycelium by a modified Chihara method towards human peripheral blood mononuclear cells (PBMCs) and peripheral granulocytes, was investigated. The Se-Le-30 fraction, an analog of lentinan, significantly inhibited the proliferation of human PBMCs stimulated with anti-CD3 antibodies or allostimulated, and down-regulated the production of tumor necrosis factor (TNF)-α by CD3+ T cells. Moreover, it was found that Se-Le-30 significantly reduced the cytotoxic activity of human natural killer (NK) cells. The results suggested the selective immunosuppressive activity of this fraction, which is non-typical for mushroom derived polysaccharides.
Subject(s)
Fungal Polysaccharides/pharmacology , Leukocytes, Mononuclear/cytology , Selenium/chemistry , Shiitake Mushrooms/chemistry , Cell Proliferation/drug effects , Down-Regulation , Granulocytes/cytology , Granulocytes/drug effects , Granulocytes/immunology , Humans , Killer Cells, Natural/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Mycelium/chemistry , Superoxides/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
In the present study a new group of derivatives of both paclitaxel and Lactarius sesquiterpenes, the N-acetylphenylisoserinates of Lactarius sesquiterpenoid alcohols, was tested for antiviral, cytotoxic, antiproliferative and immunotropic activities in vitro. Among the 13 compounds tested two, isolactarorufin 8-[ N-acetyl-(2' R,3' S)-3'-phenylisoserinate] and 3-O-ethylfurandiol 8-[ N-acetyl-(2' R,3' S)-3'-phenylisoserinate] inhibited Herpes simplex virus type 1 (HSV-1) replication at low cytotoxic concentrations. Selectivity indices were: > 12.2 and > 106.4, respectively. Both compounds decreased also the number of cell divisions. Mitotic indices of the cells submitted to these compounds were: 96/2000 and 48/1000, respectively, in comparison with control (169/2000). It seems that the antimitotic action of the compounds may be associated with their antiviral activity. Moreover, isolactarorufin 8-[ N-acetyl-(2' R,3' S)-3'-phenylisoserinate] inhibited PHA-induced T lymphocyte proliferation.
Subject(s)
Agaricales/chemistry , Antibiotics, Antineoplastic/pharmacology , Antiviral Agents/pharmacology , Cell Proliferation/drug effects , Serine/analogs & derivatives , T-Lymphocytes/drug effects , Animals , Antibiotics, Antineoplastic/analysis , Antineoplastic Agents, Phytogenic/pharmacology , Antiviral Agents/analysis , Chlorocebus aethiops , Esterification , Herpesvirus 1, Human/drug effects , Paclitaxel/pharmacology , Serine/pharmacology , Sesquiterpenes/pharmacology , Vero CellsABSTRACT
Six N-benzoylphenylisoserinates of Lactarius sesquiterpenoid alcohols, which previously showed antiviral activities, were tested for their biological properties. Their influence on the mitotic division of the cells and on selected immunological parameters, e. g., T and B lymphocyte proliferation and synthesis of the cytokines: interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) was assessed in vitro. All of the tested compounds significantly decreased the number of cell divisions. It appears that their influence on cellular divisions may be associated with anti-HSV activity. Moreover, one compound - isolactarorufin 8-epi-[N-benzoyl-(2' R,3' S)-3'-phenylisoserinate] significantly inhibited T lymphocyte proliferation and the synthesis of all tested cytokines.