RESUMO
Pseudoshikonin I, the new bioactive constituent of Lithospermi radix, was isolated from this methanol extract by employing reverse-phase medium-pressure liquid chromatography (MPLC) using acetonitrile/water solvent system as eluents. The chemical structure was determined based on spectroscopic techniques, including 1D NMR (¹H, (13)C, DEPT), 2D NMR (gCOSY, gHMBC, gHMQC), and QTOF/MS data. In this study, we demonstrated the effect of pseudoshikonin I on matrix-metalloproteinase (MMPs) activation and expression in interleukin (IL)-1ß-induced SW1353 chondrosarcoma cells. MMPs are considered important for the maintenance of the extracellular matrix. Following treatment with PS, active MMP-1, -2, -3, -9, -13 and TIMP-2 were quantified in the SW1353 cell culture supernatants using a commercially available ELISA kit. The mRNA expression of MMPs in SW1353 cells was measured by RT-PCR. Pseudoshikonin I treatment effectively protected the activation on all tested MMPs in a dose-dependent manner. TIMP-2 mRNA expression was significantly upregulated by pseudoshikonin I treatment. Overall, we elucidated the inhibitory effect of pseudoshikonin on MMPs, and we suggest its use as a potential novel anti-osteoarthritis agent.
Assuntos
Interleucina-1beta/farmacologia , Lithospermum/química , Inibidores de Metaloproteinases de Matriz/farmacologia , Metaloproteinases da Matriz/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/química , Estrutura Molecular , Inibidor Tecidual de Metaloproteinase-2/metabolismoRESUMO
As a part of an ongoing search for bioactive constituents from Korean medicinal plants, the phytochemical investigations of the twigs of Salix glandulosa afforded 12 new phenolic glycosides (1-12) and a known analogue (13). The structures of 1-13 were characterized by a combination of NMR methods ((1)H and (13)C NMR, (1)H-(1)H COSY, HMQC, and HMBC), chemical hydrolysis, and GC/MS. The absolute configuration of 13 [(1R,2S)-2-hydroxycyclohexyl-2'-O-trans-p-coumaroyl-ß-d-glucopyranoside] was determined for the first time. Compounds 1-3, 6, and 7 exhibited inhibitory effects on nitric oxide production in lipopolysaccharide-activated murine microglial cells (IC50 values in the range 6.6-20.5 µM).
Assuntos
Glicosídeos/isolamento & purificação , Fenóis/isolamento & purificação , Plantas Medicinais/química , Salix/química , Animais , Glicosídeos/química , Glicosídeos/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Fenóis/química , Fenóis/farmacologia , Caules de Planta/química , República da Coreia , EstereoisomerismoRESUMO
This study was designed to investigate the antiobesity effects of Salvia plebeia R. Br. ethanolic extracts (SPE) in mice fed high-fat diets (HFD). Male C57BL/6J mice were randomly assigned to four groups: normal diet (Chow), high-fat diet (HFD, 45% fat), HFD+SPE 200 (200 mg/kg b.w.), and HFD+SPE 400 (400 mg/kg b.w.). Extracts were administered orally every day for 8 weeks. Increases in body/fat weight and feed efficiency ratio were monitored in all mice. In addition, obesity resulting from feeding HFD to the mice was confirmed by the increase of glucose level, aspartate transaminase, alanine transaminase, triglyceride (TG), high-density lipoprotein cholesterol, very low-density lipoprotein-c, leptin, and adiponectin in blood. The SPE-treated mice gained less body and mesenteric/subcutaneous adipose tissues weights and had lower TG, very low-density lipoprotein cholesterol, leptin, and glucose level in serum, compared to the HFD group. Moreover, histopathological examinations revealed that the size of adipocytes in liver and adipose tissue was significantly decreased by SPE, compared to the HFD group. The expression of adipogenesis transcription factors (e.g., peroxisome proliferator activated receptor γ and CCAAT/enhancer binding protein α) and lipogenesis-related target genes (adipocyte fatty acid-binding protein 2, lipoprotein lipase, fatty acid synthase, and sterol regulatory element-binding transcription factor 1c) in HFD-induced obese mice was decreased by SPE treatment. These results suggest that SPE attenuates the fat accumulation in HFD-induced obese mice by suppressing the expressions of genes related to adipogenesis and lipogenesis activity. Therefore, SPE could be developed as a potential therapy for reduction of body weight and antiobesity intervention.
Assuntos
Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Salvia/química , Adiponectina/sangue , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Peso Corporal/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Dieta Hiperlipídica , Modelos Animais de Doenças , Leptina/sangue , Lipídeos/sangue , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/sangue , Obesidade/patologia , Tamanho do Órgão/efeitos dos fármacos , Distribuição AleatóriaRESUMO
PURPOSE: To assess optical quality and intraocular scattering using the Optical Quality Analysis System (OQAS) in central serous chorioretinopathy (CSC) and to determine the effects of retinal changes on optical quality. METHODS: This was a prospective, case-control study. Participants were 29 patients with diagnosis of CSC. The control group consisted of the patients' unaffected eyes. Initial logMAR visual acuity, central macular thickness (by spectral domain optical coherence tomography), and optical quality parameters including modulation transfer function (MTF) cutoff frequency, Strehl (2-dimensional) ratio, and OQAS values at 100%, 20%, and 9% contrast levels were investigated. Objective scattering index (OSI) at 4.0-mm pupil size was assessed in both eyes by using the OQAS. After 3 months of treatment, which included observation and focal laser or injections of antivascular endothelial growth factor, every CSC-affected eye was followed. Main outcome measures were differences between clinical parameters of the CSC-affected eye and those of the control eye and changes in those parameters according to the clinical course of CSC over 3 months. RESULTS: In CSC-affected eyes, the MTF cutoff was significantly reduced (P = 0.01), and OSI was significantly increased (P = 0.03). As macular thickness decreased, OSI decreased but did not become normalized compared to the control eye, nor was it statistically significantly correlated with central macular thickness change. CONCLUSIONS: Retinal change affected optical quality and intraocular scatter. Therefore, when the severity of a cataract is assessed using the OQAS, retinal status should be considered when interpreting OQAS values.