ABSTRACT
A novel octahydroindolizine alkaloid, named dendrocrepidamine (1) with an unusual 18,19,19'-cyclopropanone-dendrocrepine skeleton, was isolated from the ethanol extract of the roots of Dendrobium crepidatum, along with six known compounds (2-7). The structure of 1 was elucidated through HR-ESIMS, NMR spectroscopic data and computational calculations. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells with IC50 values in the range of 3.04-54.89 µM. In vivo, crepidatin (6) (80, 40 and 10 mg/kg) showed a significant protective effect against LPS-induced acute lung injury (ALI) in mice.
Subject(s)
Alkaloids , Dendrobium , Alkaloids/pharmacology , Animals , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide , RAW 264.7 CellsABSTRACT
OBJECTIVE: To investigate the ability of osteogenic differentiation and the expression of histone demethylases KDM6B in bone marrow mesenchymal stem cells (BMSCs) in diabetic environment. METHODS: Diabetic model rats was successfully established, and BMSCs from diabetic model rats and normal rats were isolated and cultured for further study. When cultured cells, we added high concentration of glucose and advanced glycosylation products (AGE) in the medium to imitating the diabetic environment. BMSCs were divided into 6 groups: diabetes group (derived from diabets SD rats), normal group (derived from normal SD rats), high glucose group (30 mmol/L D-glucose), normal glucose group (5.5 mmol/L D-glucose), AGE group (AGE 300 µg/mL) and BSA group (BSA 300 µg/mL). BMSCs in diabetes group were derived from diabetes SD rats, while others were derived from normal SD rats. After 7 d of osteogenic induction, the cells were examined the ability of osteogenic differentiation by alkaline phosphatase (ALP) staining, the transcription levels of Runt-related transcription factor 2 (Runx2) and KDM6B were determined by RT-PCR, and the expression levels of H3K27Me3 protein were examined by Western bolt. RESULTS: Compared with the control groups, the numbers of ALP stained cells and the mRNA levels of Runx2 and KDM6B in diabetes group, high glucose group and AGE group were all decreased (P < 0.05), while H3K27Me3 protein expression levels were all increased (P < 0.05). CONCLUSION: The ability of osteogenic differentiation of BMSCs in diabetic environment was weakened, and the expression of Runx2 mRNA was inhibited, which may be related to the increased expression of H3K27Me3 after the inhibition of KDM6B expression.
