RESUMO
Three previously undescribed compounds including a polyketide (1) and two lactams (2 and 3) were obtained from Tuber indicum. The structures of new findings were elucidated by HRESIMS, NMR as well as NMR and ECD calculations. Transcriptome analysis through RNA-seq revealed that compound 2 exhibits immunosuppressive activity. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were employed as a model to explore the effect of these compounds in immunosuppressive activity. The results showed that 2 could reduce the generation of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Western blotting analysis demonstrated that 2 could suppressed the PI3K pathway by decreasing the levels of p-PI3K and p-Akt, while increasing the levels of p-PTEN. The anti-inflammatory activity of 2 was further confirmed using a zebrafish in vivo model.
Assuntos
Ascomicetos , NF-kappa B , Fosfatidilinositol 3-Quinases , Animais , Camundongos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Peixe-Zebra/metabolismo , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismo , Lipopolissacarídeos , Óxido Nítrico/metabolismo , Perfilação da Expressão Gênica , Células RAW 264.7RESUMO
Two new phenolic glycosides 7R,8R-threo-4,7,9,9'-tetrahydroxy-3-methoxy-8-O-4'-neolignan-3'-O-(3''-α-L-arabinofuranosyl)-ß-D-glucopyranoside. (1), 4-(4'-hydroxyphenyl)-2-butanone-4''-O-(6-ß-D-xylosyl)-ß-D-glucopyranoside (2), along with two known related analogues 7R,8R-threo-4,7,9,9'-tetrahydroxy-3-methoxy-8-O-4'-neolignan-3'-O-ß-D-glucopyranoside (3), 4-(4'-hydroxyphenyl)-2-butanone-4'-O-ß-D-glucopyranoside (4) were obtained from the roots of Sanguisorba officinalis. Combined with acid hydrolysis derivatization, the absolute configurations of these new compounds were elucidated by comprehensive analyses of spectroscopic data including nuclear magnetic resonance (NMR), electrospray ionization high resolution mass (HRESIMS) as well as circular dichroism (CD). Compounds 1-4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).