Anti-inflammatory compounds in human peripheral blood mononuclear cells from dendrobium species

Abstract

In these studies, four new compounds including three phenanthrene derivatives (dendrocrumenols A, B and D) and one fluorenone (dendrocrumenol C) and four known compounds including gigantol, 3,7-dihydroxy-2,4,8-trimethoxyphenanthrene, densiflorol B�and cypripedin were isolated from Dendrobium crumenatum Sw. Each structure of isolated compounds from D. crumenatum was elucidated by spectroscopic data. These isolated compounds were then evaluated for anti-inflammatory effects�in human peripheral blood mononuclear cells (PBMCs). Among the tested compounds, dendrocrumenols B and D showed the most promising anti-inflammatory effects�through inhibition of tumor necrosis factor tumor (TNF) and interleukin-2 (IL-2) in monocytes and T cells. The deep immune profiling using high-dimensional single-cell mass cytometry (CyTOF) could confirm the anti-inflammatory effects based on immunomodulation of dendrocrumenol D through the decreasing of activated T cell population in phorbol-12-myristate-13-acetate and ionomycin (PMA/Iono) stimulation in human PBMCs. Next, the seven known bibenzyls isolated from Dendrobium plants were investigated the immunomodulatory effects in lipopolysaccharide (LPS)-induced human PBMCs. Two bibenzyls, moscatilin and crepidatin, exhibited the strongest inhibitory effect of TNF-expressed monocytes. The deep immune profiling using CyTOF could confirm the anti-inflammatory activity based on�immunomodulation effect of crepidatin through reduction of NK cells, pSTAT5+ non-classical monocytes and monocytes expressing co-stimulatory molecule CD86.