RESUMO
Icariin (ICA) has been used as a promising antiaging drug; however, its underlying molecular mechanism is yet to be elucidated. The present study aimed to determine the antiaging molecular mechanisms of ICA. Dgalactose (Dgal) was used to generate a cell aging model. IMR90 human lung fibroblasts were pretreated with different concentrations of ICA (1, 2, 4, 8 and 16 µmol/l) for 6 h and subsequently incubated with Dgal (200 mmol/l) at 37ËC for 72 h. Senescence of IMR90 cells was assessed by senescenceassociatedßgalactosidase (SAßGal) staining assay. Cell viability, and the expression levels of p53/p21, sirtuin (SIRT) 1/6 and p50/p65 were determined via the MTT assay and western blotting respectively. The results demonstrated that Dgal notably increased the proportion of SAßGalpositive cells and decreased the viability of IMR90 cells; however, pretreatment with ICA reversed the effects of Dgal on IMR90 cells in a concentrationdependent manner. Furthermore, it was also demonstrated that the activation of p53/p21 and nuclear factorκB (NFκB) signaling, and downregulation of SIRT1/6 may be involved in IMR90 cells, in Dgalinduced aging and ICA may effectively prevent IMR90 cells from these changes induced by Dgal. Taken together, the results of the present study suggest that the antiaging molecular mechanisms of ICA may be associated with the regulation of the SIRT1/NFκB pathway.
Assuntos
Senescência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Flavonoides/farmacologia , Pulmão/citologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Envelhecimento/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Galactose/efeitos adversos , HumanosRESUMO
Eight compounds were isolated from the ethyl acetate extraction of Prunus mume by column chromatography. On the basis of physicochemical properties and spectrum analysis, these compounds were identified as isoquercitrin-6â³-O-benzoate(1), pinoresinol(2), naringin(3), ethyl-ß-D-glucopyranoside(4), astragalin(5), quercetin(6), hypericin(7), and rutin(8). Among them, compound 1 was a new natural product, and compounds 2-5 were isolated from this plant for the first time. In vitro study, compounds 1, 3, 5-8 could significantly increase the cell survival ratio.
Assuntos
Compostos Fitoquímicos/análise , Extratos Vegetais/química , Prunus/química , Acetatos , SolventesRESUMO
A chemical investigation of the fibrous roots of Anemarrhena asphodeloides Bge. led to the isolation of four benzophenones, including one new compound (1) and three known ones (2-4). Comprehensive 1D, 2D NMR and HRESIMS data established the structures of the isolated compounds. The absolute configurations were determined by comparison of the calculated optical rotation (OR) with experimental data. All the isolates were evaluated for their cytotoxicities on hepatocellular carcinoma cell lines (HepG2 and Hep3B). Compound 1 showed strong cytotoxicity against HepG2 and Hep3B cells, with IC50 values at 153.1 and 180.6 nM. Through MTT assay, flow cytometry and Western blot analysis, compound 1 demonstrated the ability to stimulate apoptosis via the NF-κB signaling pathway in HepG2 cells. These benzophenones are potential lead compounds for the development of better treatments for hepatocellular carcinoma.
Assuntos
Anemarrhena/química , Antineoplásicos Fitogênicos/farmacologia , Benzofenonas/farmacologia , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Benzofenonas/química , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , NF-kappa B/metabolismo , Extratos Vegetais/química , Raízes de Plantas/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Sijunzi decoction (SJZD) is a well known traditional Chinese prescription used for the treatment of gastrointestinal disorders and immunity enhancement. It has been found to indeed improve life quality of chemotherapy patients and extensive used in clinical conbined with chemotherapeutics for the treatment of cancer. AIM OF THE STUDY: The aim of this study was to investigate the preventive effect of the immunotoxicity of SJZD on mitomycin C (MMC) and the metabolic mechanism of action. MATERIALS AND METHODS: NMR and MS-based metabolomics approaches were combined for monitoring MMC-induced immunotoxicity and the protective effect of SJZD. Body weight change and mortality, histopathological observations and relative viscera weight determinations of spleen and thymus, sternum micronucleus assay and hematological analysis were used to confirm the immunotoxicity and attenuation effects. An OPLS-DA approach was used to screen potential biomarkers of immunotoxicity and the MetaboAnalyst and KEGG PATHWAY Database were used to investigate the metabolic pathways. RESULTS: 8 biomarkers in plasma samples, 19 in urine samples and 10 in spleen samples were identified as being primarily involved in amino acid metabolism, carbohydrate metabolism and lipid metabolism. The most critical pathway was alanine, aspartate and glutamate metabolism. CONCLUSIONS: The variations in biomarkers revealed the preventive effect of the immunotoxicity of SJZD on MMC and significant for speculating the possible metabolic mechanism.