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The trace chemical components in functional Monascus rice were studied to explore the potential bioactive substances. MCI column, Sephadex LH-20 gel, and preparative liquid chromatography were used to purified the ethyl acetate extract from functional Monascus rice. Two novel pyridine Monascus pigments were isolated and identified, named monascopyridine G (1) and monascopyridine H (2), respectively based on extensive mass spectrometry (MS), infrared radiation (IR), and nuclear magnetic resonance (NMR) analysis. The molecular docking experiments between compounds 1 and 2 and peroxisome proliferators-activated receptor-gamma (PPARγ) showed that they exhibited obvious binding force with the receptor protein. Besides, the biosynthetic pathways of the two compounds were proposed, which provide a valuable reference for the selective production of these potential bioactive substances.
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Background Long-term exposure to arsenic can cause liver injury of varying degrees. Mitochondrial damage may be an early key event of arsenic-induced liver injury. Silent mating type information regulation 2 homolog 1 (SIRT1)/ recombinant peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important pathway regulating mitochondrial mass and function. However, whether arsenic-induced liver injury is related to mitochondrial dysfunction mediated by SIRT1/PGC-1α pathway remains unclear. Objective To investigate potential effects of sodium arsenite (NaAsO2) on mitochondrial function and expressions of SIRT1/PGC-1α pathway-related proteins in human normal liver cell. Methods Human normal liver cells (MIHA cells) were used as the research object. MIHA cells were treated with different concentrations of NaAsO2 (0, 5, 10 and 20 μmol·L−1) for 24 h, and the cells were collected for study. The ultrastructure of mitochondria was observed by transmission electron microscopy, adenosine triphosphate (ATP) concentration by fluorescence method, mitochondrial membrane potential (MMP) level by flow cytometry, and SIRT1, PGC-1α and their downstream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) protein expression levels by Western blotting. One-way analysis of variance and trend test were used for data statistical analysis. Results The viability of MIHA cells decreased gradually with the increase of NaAsO2 concentration (F=6495.47, P<0.001). The transmission electron microscope observation showed that the size of mitochondria in the 10 μmol·L−1 NaAsO2 treatment group was different, and the mitochondria were swollen or elongated in a rod-like shape. The mitochondria in the 20 μmol·L−1 NaAsO2 treatment group swelled like air spheres or vacuoles. The ATP concentration and MMP level of MIHA cells gradually decreased with the increase of NaAsO2 concentration (Ftrend of ATP=172.28, Ftrend of MMP=59.91, both Ps<0.001). Compared with the control group, the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM were not significantly changed in the 5 μmol·L−1 NaAsO2 treatment group, while the protein expression levels of SIRT1, PGC-1α, and TFAM were decreased in the 10 μmol·L−1 NaAsO2 treatment group, and the protein expression levels of SIRT1, PGC-1α, and NRF1 were decreased in the 20 μmol·L−1 NaAsO2 treatment group. The results of trend test showed that the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM decreased gradually with the increase of NaAsO2 concentration (Ftrend of SIRT1=47.07, P<0.001; Ftrend of PGC-1α=15.17, P<0.01; Ftrend of NRF1=13.54, P<0.01; F trend of TFAM=4.20, P<0.05). Conclusion The down-regulation of SIRT1/PGC-1α and its downstream NRF1 and TFAM may be involved in NaAsO2-induced mitochondrial dysfunction in liver cells.
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El objetivo de este estudio fue determinar la prevalencia del polimorfismo Pro12Ala del gen PPARgamma2 en individuos no emparentados con síndrome metabólico de la ciudad de Maracaibo. Se seleccionaron 50 individuos (22 con síndrome metabólico y 28 sin síndrome metabólico) entre 22 y 58 años. A cada individuo se le realizó una evaluación clínica, nutricional y bioquímica. Para analizar la secuencia de la variante Pro12Ala del gen PPAR se empleó PCR y digestión enzimática de los fragmentos de restricción del polimorfismo (PCR-RFLP). En los individuos con síndrome metabólico el porcentaje de portadores del alelo Ala fue de 13,6%, mientras que en el grupo sin síndrome metabólico fue de 32,14%. La frecuencia para el alelo Ala del polimorfismo Pro12Ala fue de 0,12 y para el alelo Pro fue de 0,88. Los individuos con síndrome metabólico y portadores del alelo Ala presentaron niveles más bajos de triglicéridos y col-HDL más alto. Se concluye que la presencia del alelo Ala en individuos con síndrome metabólico mostró un efecto protector sobre el perfil lipídico.
The aim of this paper was to determine the prevalence of the polymorphism pro12ala in non-related individuals with metabolic syndrome from Maracaibo-Venezuela. Fifty subjects (22 with metabolic syndrome and 28 without metabolic syndrome) between 22 to 58 years of age were selected. For each individual, biochemical, nutritious, and clinical evaluations were carried out. PCR and restriction-fragment length polymorphism enzyme digestion were used to analyze the Pro12Ala sequence variant of the PPAR gene. The distribution of the Ala allele was 13.6% in the individuals with metabolic syndro- and 32.14% in the group without metabolic syndrome. The frequency distributions of the PPAR gamma sequence variants were 0.12 for Ala variant and 0.88 for Pro. The subjects with the metabolic syndrome and carriers of the Ala 12 allele had lower concentration of triglycerides and higher HDL-C. It can be concluded that the Ala12 allele in individuals with metabolic syndrome had a protective effect on the lipid profile.
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Humans , Male , Female , Adult , Middle Aged , Polymorphism, Genetic/genetics , Metabolic Syndrome/epidemiology , Venezuela , Metabolic Syndrome/blood , Peroxisome Proliferator-Activated Receptors/bloodABSTRACT
Objective To explore the effects and mechanism of peroxisome proliferators activated receptor-gamma(PPAR-γ)and its ligand rosiglitazone on ischemia-reperfusion injury of the donor bile ducts.Method Forty-two SD rats were randomly divided into three groups with fourteen rats in each:the sham operation group (SO),ischemia-reperfusion(I/R)group and I/R+rosiglitazone group(I/R+Ros).The animal model of is-chemia-reperfusion occurred in the orthotopically transplanted liver was used.Tne signal pathway of iuflanunatory response of bile duets of the transplanted hver and the variations of associated cytokines were detected by the signal transduction pathway-finder gene array and cytokine antibody chips.The pathological changes and the biochemical markers of the donor liver were assessed by histopathological score and the estimation of the functional changes of some other organs.Data were analyzed by using SPSS version 10.0 software package.Statistical analysis was car-ried out by using one-way anova and Bonferroni test.Results Compared with the SO group and I/R+Ros group.the expression of NF-кB gene of I/R group to more than two times,and the levels of IL-1α,IL-1β and TNF-α pro-tein expressions in I/R group went up over double too.Compared with I/R group,the histopathological score and the biochemical markers of I/R+Ros group were significantly lower (P＜0.05,P＜0.01,respectively).Con-clusions PPAR-γ and its ligand rosiglitazone have protective effects on ischemia-reperfusion injury to donor bile ducts.The mechanism may be attributed to decrease in the release of inflammatory mediators(IL-1α,IL-1β,TNF-α and so on)resulted from the down-expression of decreased due to NF-кB.
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The expressions of NF-κB and PPARγ were increased in adipose tissue of insulin resistant rats.The angiotensin receptor blocker decreased NF-κB protein expression by 21%,increased PPARγ protein expression by 28%and diminished adipocyte size,suggesting that these findings may be involved in the improvement of obesity-induced inflammation and insulin resisitance.
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Objective To observe the protective effect of sodium hyaluronate (Na-HA),and its effects on mRNA expression of peroxisome proliferators-activated receptor gamma (PPAR-γ) in cartilage of rabbit osteoarthritis (OA) model.Methods Forty eight white rabbits were divided into A,B,C groups randomly.Group A were normal controls,groups B and C were underwent unilateral anterior cruciate ligament transection (ACLT).The rabbits in group B were injected normal saline after ACLT;Group C rabbits received intra-articular 1% sodium hyaluronate (HA) injections 5 weeks after surgery,0.3 ml once a week.At week 11 after the surgery,all rabbits were sacrificed.The cartilage changes on the medial femoral condyles were graded.Cartilage sections were stained with safranin-O and HE,mRNA expression of PPAR-γ was detected by real time polymerase chain reaction (Real Time-PCR).Results Cartilage degeneration in group B was significantly more severe than in groups A and C.The grey value of Safranin-O of B group were higher than groups A and C.Expression of PPAR-γ mRNA in group B was higher than that in groups A and C.Conclusion NaHA has a protective effect on articular cartilage degeneration,and the inhibitory effect on PPAR-γ mRNA expression may be one of the therapeutic mechanism of Na-HA.
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PURPOSE: The purpose of this study was to study the protective effect and influence of sodium hyaluronate (Na-HA) on mRNA expression of peroxisome proliferators-activated receptor gamma (PPAR-gamma) in cartilage of rabbit osteoarthritis (OA) model. MATERIALS AND METHODS: Forty eight white rabbits were randomly divided into A, B, and C groups. Group A was normal control group, B and C groups underwent unilateral anterior cruciate ligament transection (ACLT). The rabbits in group B were injected normal saline after ACLT; and Group C received intraarticular1% sodium hyaluronate (HA) injection 5 weeks after surgery, 0.3 mL once a week. At 11th week after surgery, all the rabbits were sacrificed. The cartilage changes on the medial femoral condyles were graded separately. Cartilage sections were stained with safranin-O and HE, and messenger RNA (mRNA) expression of PPAR-gamma was detected by using real time polymerase chain reaction (Real Time-PCR). RESULTS: Cartilage degeneration in group B was significantly more severe than in A and C injection group. The grey value of Safranin-O of B group was higher than A and C groups. Expression of PPAR-gamma mRNA in group B was higher than group A and C. CONCLUSION: This study shows that Na-HA has a protective effect on articular cartilage degeneration, and the inhibitory effect on the PPAR-gamma mRNA expression may be one of therapeutic mechanism of Na-HA.
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Animals , Rabbits , Cartilage/drug effects , Gene Expression/drug effects , Hyaluronic Acid/pharmacology , Microscopy , Osteoarthritis/drug therapy , PPAR gamma/genetics , RNA, Messenger/genetics , Random Allocation , Reverse Transcriptase Polymerase Chain Reaction , Viscosupplements/pharmacologyABSTRACT
Objective To study the effects of atorvastatin on the expressions of peroxisome proliferators-activated receptor gamma(PPAR?)and matrix metalloproteinase-9(MMP-9)in atherosclerosis(AS) tissue.Methods Atherosclerotic rabbit models on aortas were established with the high-cholesterol diet,and animals were divided into control,model and atorvastatin groups(n=8).The expressions of PPAR? and MMP-9 and the effects of atorvastatin on them were observed by means of immunohistochemistry.Results The expression of PPAR? in model group(14.38%?2.58%)was higher than that in control group(7.82%?0.96%)(P
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0.05).Conclusion A silent C161 T polymorphism of PPAR? gene might not be genetic markers of osteoporosis,which might not be employed to screen the high risk population of osteoporosis in Chinese women of Han nationality.
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Objective To study the effects of peroxisome proliferators-activated receptor (PPAR) ? on the growth of human hepatocellular carcinoma cells and explore the roles of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and phospho-Akt in this process. Methods SMMC-7721 cells were treated with 15-d-PGJ2 or pioglitazone, which were two kinds of PPAR? ligands, at different concentrations. The viability of SMMC-7721 cells was evaluated by MTT assay. The cell cycle was analyzed by flow cytometry. PTEN mRNA level was determined by RT-PCR. The protein expressions of PTEN and pAkt were measured by Western blot analysis. Results It was demonstrated through MTT assay that both 15-d-PGJ2 and pioglitazone had an inhibitory effect on the growth of SMMC-7721 cells in a time- and dose- dependent manner. According to flow cytometry detection, more cells were arrested in G0/G1 phase. Increased expression of PTEN mRNA was detected in 15-d-PGJ2 or pioglitazone-treated cells through RT-PCR. Increased expression of PTEN protein and decreased expression of pAkt were confirmed by Western blot analysis. Conclusion The ligands of PPAR? could inhibit SMMC-7721 cells proliferation in a time- and dose- dependent manner. The upregulation of PTEN may be involved in the underlying mechanism.
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Objective To observe the effect of peroxisome proliferators activated receptor gamma(PPAR-?)on phenotypic transforming of vascular smooth muscle cells(VSMC)in hypertension.Methods Spontaneous hypertension rats(SHR)and WKY rats both aged 4 months were included.SHR rats as well as WKY rats were divided to be fed with normal chow,and chow added with rosiglitazone(10 mg?kg-1?d-1)for 16 weeks.VSMC were isolated from SHR rats and WKY rats and cultured by patch-attaching method,then respectively divided into 3 groups after treated with genetic recombination technology:normal VSMC,PPAR? overexpressed VSMC and PPAR? silenced VSMC.Expressions of OPN and ?-SMA,which respectively represent the undifferentiated and differentiated VSMC,were detected by Western blotting.Cell proliferation was determined by detecting DNA synthesis and cell counting.The changes of arteries were evaluated pathologically.Results Rosiglitazone decreased blood pressure and ameliorated vascular remodeling of aorta in SHR rats.Aorta of SHR showed an upregulation of OPN and downregulation of ?-SMA,which could be inhibited by rosiglitazone.VSMC from SHR rats showed an upregulation of OPN and downregulation of ?-SMA,and increased cell proliferation.These changes were all inhibited by rosiglitazone.In the cells that overexpressed PPAR?,the cell proliferation rate was lower,and the expressions of OPN and ?-SMA were depressed,compared with the corresponding control cells.Conclusion PPAR-? could inhibit the phenotypic transforming of VSMC,and this might be responsible for the amelioration of vascular remodeling in hypertension.