Mechanism of Magnoliae Officinalis Cortex in treatment of peptic ulcer based on network pharmacology and molecular docking / 中国中药杂志

Magnoliae Officinalis Cortex(Houpo) can treat peptic ulcer disease(PUD), the mechanism of which remains unclear. In this study, network pharmacology and molecular docking were employed to predict the mechanism of Houpo in the treatment of PUD. Through literature review and TCMSP screening, 15 main active ingredients were obtained. The SwissTargetPrediction database was used to predict the potential targets of the ingredients, and Therapeutic Target Database(TTD), DrugBank, and Human Phenotype Ontology(HPO) to screen the disease-related targets. A total of 49 potential targets were obtained by the intersection of active ingre-dients-related targets and disease-related targets. Cytoscape 3.6.1 was employed to construct the protein-protein interaction network for the targets with high confidence(score>0.700) screened out by STRING. The DAVID database was used for GO and KEGG pathway enrichment of potential targets. GO enrichment analysis showed that the treatment mechanism was mostly related to nuclear receptor activity, ligand-activated transcription factor activity, and G protein-coupled acetylcholine receptor activity. KEGG enrichment analysis found that Houpo could regulate material metabolism, endocrine system, p53 signaling pathway, and PPAR signaling pathway. Molecu-lar docking verified that all 15 ingredients had good binding activities with key targets(CHRM1, CHRM2, FABP1, mTOR, and STAT3). The results mean that Houpo can treat PUD by participating in cell metabolism, inhibiting inflammatory cytokines, and regulating cell proliferation and apoptosis.

Pharmacological Activation of RXR-α Promotes Hematoma Absorption via a PPAR-γ-dependent Pathway After Intracerebral Hemorrhage / 神经科学通报·英文版

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.

Pharmacological Activation of RXR-α Promotes Hematoma Absorption via a PPAR-γ-dependent Pathway After Intracerebral Hemorrhage / 神经科学通报·英文版

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.

Protective Effect of Formula of Gougancat Decoction on Acute Liver Injury Induced by Carbon Tetrachloride in Rats / 中国实验方剂学杂志

Objective: To explore the protective effect of formula of Gougancai decoction (FGD) on acute liver injury induced by carbon tetrachloride (CCl4) in rats, in order to provide basis for the development of pharmaceutical preparations or healthcare products. Method: Sixty rats were randomly divided into normal group, Silymarin group (120 mg·kg-1) and FGD groups (475, 950, 1 900 mg·kg-1). The normal group and the model group were given equal volume of saline by gavage, while the other groups were administered with the corresponding dose of drugs according to the body weight. After 10 days, the acute liver injury model was established with 12% carbon tetrachloride peanut oil solution (5 mL·kg-1), except the normal group. All of the rats were put to death to collect serum and liver tissues. The contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected by biochemical methods, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in liver tissues were determined by enzyme-linked immunosorbnent assay(ELISA). Nuclear factor-κB (NF-κB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expression in liver tissues were detected by Western blot, and htoxylin eosin (HE) staining was used to observe the variation of liver histopathological. Result: Compared with the normal group, the serum activities of AST, ALT, ALP and the content of TBIL, MDA in the model group were significantly increased (Pα, IL-1β, IL-6 in liver tissue were remarkably increased (PPκB was enhanced in liver tissue (Pγ was down-regulated (PPPα, IL-1β, IL-6 (PPκB (PPγ (PPConclusion: FGD has a protective effect on CCl4-induced acute liver injury in rats, and its mechanism may be related to the activation of PPAR-γ and the inhibition of NF-κB signaling pathway, with anti-inflammatory and anti-oxidative effects.

Role of PPAR-γ-regulated autophagy in genistein-induced inhibition of hepatic stellate cell activation / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of genistein on activation of hepatic stellate cells (HSCs) and the role of the autophagy pathway regulated by PPAR-γ in mediating this effect.@*METHODS@#Cultured HSC-T6 cells were exposed to different concentrations of genistein for 48 h, and HSC activation was verified by detecting the expressions of -SMA and 1(I) collagen; autophagy activation in the cells was determined by detecting the expressions of LC3-II and p62 using Western blotting. The autophagy inhibitor 3-MA was used to confirm the role of autophagy in genistein-induced inhibition of HSC activation. A PPAR-γ inhibitor was used to explore the role of PPAR-γ in activating autophagy in the HSCs.@*RESULTS@#Genistein at concentrations of 5 and 50 μmol/L significantly inhibited the expressions of -SMA and 1(I) collagen ( < 0.05), markedly upregulated the expressions of PPAR-γ and the autophagy-related protein LC3-II ( < 0.05) and significantly down-regulated the expression of the ubiqutin-binding protein p62 ( < 0.05) in HSC-T6 cells. The cells pretreated with 3-MA prior to genistein treatment showed significantly increased protein expressions of -SMA and 1(I) collagen compared with the cells treated with genistein only ( < 0.05). Treatment with the PPAR-γ inhibitor obviously lowered the expression of LC3-II and enhanced the expression p62 in genistein-treated HSC-T6 cells, suggesting the activation of the autophagy pathway.@*CONCLUSIONS@#PPAR-γ- regulated autophagy plays an important role in mediating genistein-induced inhibition of HSC activation .

The dimerization of -tetrahydrocannabinolic acid A (THCA-A)

The renewed interest in dimeric salicylates as broad-spectrum anti-inflammatory and anti-diabetic agents provided a rationale to investigate the dimerization of the substituted salicylate -tetrahydrocannabinolic acid (THCA-A, ) as a strategy to solve its instability to decarboxylation and to generate analogues and/or pro-drugs of this native pre-cannabinoid. Activation of the carboxylic group with the DCC-HOBt-DMAP protocol afforded a high yield of the OBt ester , that was next converted into the highly crystalline di-depsidic dimer upon treatment with DMAP. The mono-depsidic dimer was also formed when the reaction was carried out with partially decarboxylated THCA-A samples. The structure of the depsidic dimers was established by spectroscopic methods and by aminolysis of into the pre-cannabinoid amide . Both dimers showed excellent shelf stability and did not generate significant amounts of -THC upon heating. However, only the didepsidic dimer activated PPAR-, the major target of pre-cannabinoids, but strong binding to serum proteins abolished this activity, also shielding it from the action of esterases.

Inhibition of miR-128 Abates Aβ-Mediated Cytotoxicity by Targeting PPAR-γ via NF-κB Inactivation in Primary Mouse Cortical Neurons and Neuro2a Cells

PURPOSE: Alzheimer's disease (AD) is the sixth most common cause of death in the United States. MicroRNAs have been identified as vital players in neurodegenerative diseases, including AD. microRNA-128 (miR-128) has been shown to be dysregulated in AD. This study aimed to explore the roles and molecular mechanisms of miR-128 in AD progression. MATERIALS AND METHODS: Expression patterns of miR-128 and peroxisome proliferator-activated receptor gamma (PPAR-γ) messenger RNA in clinical samples and cells were measured using RT-qPCR assay. PPAR-γ protein levels were determined by Western blot assay. Cell viability was determined by MTT assay. Cell apoptotic rate was detected by flow cytometry via double-staining of Annexin V-FITC/PI. Caspase 3 and NF-κB activity was determined by a Caspase 3 Activity Assay Kit or NF-κB p65 Transcription Factor Assay Kit, respectively. Bioinformatics prediction and luciferase reporter assay were used to investigate interactions between miR-128 and PPAR-γ 3′UTR. RESULTS: MiR-128 expression was upregulated and PPAR-γ expression was downregulated in plasma from AD patients and amyloid-β (Aβ)-treated primary mouse cortical neurons (MCN) and Neuro2a (N2a) cells. Inhibition of miR-128 decreased Aβ-mediated cytotoxicity through inactivation of NF-κB in MCN and N2a cells. Moreover, PPAR-γ was a target of miR-128. PPAR-γ upregulation attenuated Aβ-mediated cytotoxicity by inactivating NF-κB in MCN and N2a cells. Furthermore, PPAR-γ downregulation was able to abolish the effect of anti-miR-128 on cytotoxicity and NF-κB activity in MCN and N2a cells. CONCLUSION: MiR-128 inhibitor decreased Aβ-mediated cytotoxicity by upregulating PPAR-γ via inactivation of NF-κB in MCN and N2a cells, providing a new potential target in AD treatment.

Study on the mechanism of PPAR-γ dependent immunological idiosyncrasy liver injury induced by Polygonum multiflorum / 药学学报

To investigate the effects of peroxisome proliferator-activated receptor gamma(PPAR-γ)on the liver injury of Polygonum multiflorum, we established a model of immunological idiosyncrasy liver injury induced by lipopolysaccharide. The 70 Sprague-Dawley(SD)rats were randomly divided into control group, LPS group(2.8 mg·kg-1), PM group(crude drug, 2.16 g·kg-1), PPAR-γ agonist group(pioglitazone, 0.5 mg·kg-1), PM+LPS group(crude drug 2.16 g·kg-1, 2.8 mg·kg-1), PPAR-γ agonist+LPS group(0.5 mg·kg-1, 2.8 mg·kg-1)and PM+LPS+PPAR-γ agonist group(crude drug, 2.16 g·kg-1, 2.8 mg·kg-1, 0.5 mg·kg-1). The rats were orally given PM, once a day for consecutive 2 days. The control rats were given the same amount of distilled water. Liver injury was induced by intravenous injection of LPS. Sodium pentobarbital was injected intraperitoneally for anesthesia, and liver samples were collected together with blood. The plasma levels of alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6)and interferon-γ(IFN-γ)were measured. Pathological changes and hepatocellular apoptosis were examined by liver biopsy, and immunohistochemical observation of liver tissue expression of PPAR-γ and NF-κB p65. A negative correlation was observed between the expression of PPAR-γ in hepatic tissue and liver injury of Polygonum multiflorum. PPAR-γ agonist significantly reduced the PM-induced idiosyncratic liver injury in rats according to serum ALT and AST(P < 0.05), reduced liver pathological injury and hepatocyte apoptosis, decreased serum TNF-α and other inflammatory cytokines(P < 0.05), liver tissue PPAR-γ expression, and inhibited expression of NF-κB p65(P < 0.05). The results suggest that the occurrence of immunological idiosyncrasy liver injury of PM is related to inhibition of the PPAR-γ pathway and elevation of inflammatory factors. PPAR-γ agonist can reverse the idiosyncratic liver injury induced by PM, and provide a reference for elucidating mechanism of idiosyncratic liver injury induced by Polygonum multiflorum.

Effects of myocardial PPAR-gamma expression change on reperfusion arrhythmias in ischemia/reperfusion rats / 重庆医学

Objective To investigate the effects of PPAR-gamma expression on reperfusion arrhythmias in different precon ditioning myocardial ischemia/reperfusion(I/R) animal model.Methods Thirty-two SD rats were randomly divided into 4 groups(n =8):rosiglitazone+ I/R group (ROS group),GW9662 + I/R group(GW group),I/R group and sham group (Sham group).The I/ R animal model was constructed by ligation of the left anterior descending coronary artery,with ischemia for 30 min and reperfusion for 120 min.The dynamic limb Ⅱ lead electrocardiogram monitoring was performed;PPAR-gamma mRNA was detected by fluorescent quantitative PCR and the change of PPAR-gamma protein expression was detected by Western blot.Results The increasing range of QRS wave width detected before operation,at 30 min of ischemia,at 1,2 h of reperfusion from large to small were in turn the ROS group,I/R group,GW group and Sham group;the reperfusion arrhythmia score in the ROS group was significantly higher than that in the other groups(P＜0.05),while the GW group was relatively reduced.The expression level of PPAR-gamma mRNA in the ROS group detected by fluorescent quantitative PCR was significantly up-regulated(P＜0.05),while which in the GW group was down-regulated compared with the I/R group and ROS group(P＜0.05).The expression of PPAR-gamma protein was similar to that of PPAR-gamma mRNA.Conclusion Up-regulation of myocardial PPAR-gamma expression may increase the occurrence of reperfusion arrhythmias in myocardial I/R animal model.

Effects of Gegenqinlian Colon Positioning Tablet on Colon Tissue PPAR-γ,NF-κB p65 Protein Expressions of Model Rabbits with Damp-heat Type Ulcerative Colitis / 中国药房

OBJECTIVE:To observe the effects of Gegenqinlian colon positioning tablet(GGQLJC)on colon tissue PPAR-γ, NF-κB p65 protein expressions of model rabbits with damp-heat type ulcerative colitis(UC). METHODS:56 rabbits were random-ly divided into normal group(normal saline),model group(normal saline),sulfasalazine tablet(SASP)group(positive control, 0.300 g/kg),Gegenqinlian tablet (GGQL) group (0.225 g/kg) and GGQLJC high-dose,medium-dose,low-dose groups (1.036, 0.518,0.259 g/kg),8 in each group. Except for normal group,rabbits in other groups were cultured for damp-heat-type UC mod-el,intragastrically administrated in the second day of last administration,once a day,for 14 d. Disease activity index(DAI),co-lonic mucosal damage index (CMDI),histological damage (TDI) were scored;colon,spleen and thymus indexes were deter-mined;PPAR-γ,NF-κB p65 protein expressions in colon tissue were detected. RESULTS:Compared with normal group,DAI, CMDI,TDI scores and spleen index,colon index,NF-κB p65 protein level in colon tissue in model group were significantly in-creased(P<0.01);thymus index,PPAR-γprotein level in colon tissue were significantly reduced(P<0.01). Compared with mod-el group,above-mentioned indexes in each administration group were significantly improved (P<0.05 or P<0.01). Compared with GGQL group,DAI and TDI scores,spleen index,colon index,NF-κB p65 protein level in colon tissue in SASP group, GGQLJC high-dose,medium-dose groups were significantly decreased (P<0.05);PPAR-γ protein level in colon tissue in SASP group,GGQLJC high-dose,medium-dose groups were significantly increased (P<0.05 or P<0.01). CONCLUSIONS:GGQLJC has certain improvement effects on model rabbits with damp-heat type UC,which is superior to GGQL. The mechanism may be re-lated to increasing PPAR-γprotein level and decreasing NF-κB p65 protein level in colon tissue.

Cardioprotection and mechanism of embelin in sepsis mice model / 预防医学

Objective To observe the effect of embelin on the cardiac injury in sepsis mice model, and to explore whether PPAR-participates in the mechanism of cardioprotection of embelin.Methods Male mice were randomly divided into five groups.Control group were received PBS i.p.injection.Sepsis model group were received LPS (10 mg/kg) i.p.injection.Embelin treatment groups were received LPS (10 mg/kg) i.p.injection, and after 30 min different doses of embelin were given (5, 10, and 20 mg/kg, i.p.).Results The serum cTnI level and TNF-α、NF-κB protein in low dose embelin (5 mg/kg) treatment mice was not different with that of the sepsis mice.But the serum cTnI level and TNF-α、NF-κB protein in middle and high doses embelin (10, 20 mg/kg) treatment mice was lower than that of sepsis mice, and the expression of PPAR-γ was higher(P<0.05).Conclusion Embelin could protect against sepsis-induced cardiac injury.The mechanism might be involved in the upregulation of PPAR-γ protein, inhibition of NF-κB activation,and reduction of TNF-α level.

Effect of regulating peroxisome proliferator-activated receptor γ on soluble endoglin expression in first-trimester trophoblasts / 中华围产医学杂志

Objective To investigate the effect of regulating peroxisome proliferator-activated receptor γγ (PPAR γ) on soluble endoglin (sEng) expression in first-trimester trophoblasts via an in vitro study.Methods Chorionic villus were collected from 20 samples of first-trimester artificial abortion in Peking University First Hospital from July 1 st to 31 st,2016.Primary culture of trophoblast cells was performed.Trophoblast cells from each sample were divided into three groups,which were PPAR γ antagonist group,PPAR γ antagonist and PPAR γ agonist group,and control group.Supematant sEng level was detected in each group by enzyme linked immunosorbent assay (ELISA).Paired-sample t test was used for statistical analysis.Results Compared with the control group,trophoblast cells in the PPAR γ antagonist group grew slower and were reduced in number.No significant difference in growth or morphology of trophoblast cells was observed between the PPAR γγ antagonist and PPAR γγ agonist group and the control group.Supernatant sEng level was elevated in the PPAR γ antagonist group,but was not significantly changed in the PPAR γ antagonist and PPAR γ agonist group as compared with that in the control group [(124.1 23.8) vs (94.0± 12.7) pg/ml,t=-4.31,P＜0.05;(87.1 ± 10.6) vs (94.0± 12.7) pg/ml,t=1.62,P=0.12).Conclusions Suppression of PPAR γ promotes sEng expression in trophoblast cells and that can be reversed by PPAR γ agonist.

Interaction of polymorphisms of TNF-αgene promoter-308G/A and PPAR-γ2 gene-C34G with acute pancreatitis and its severity degree / 西安交通大学学报(医学版)

ABSTRACT:Objective To investigate the interaction of polymorphisms of TNF-αgene promoter-308G/A and PPAR-γ2 gene-C34G with acute pancreatitis (AP)and its severity degree.Methods Totally 150 mild acute pancreatitis(MAP),150 moderately severe acute pancreatitis(MSAP)and 150 severe acute pancreatitis(SAP)cases were selected for this study,and 450 healthy persons as control group.The genetic polymorphisms of TNF-αgene promoter-308G/A and PPAR-γ2 gene-C34G were analyzed by the technique of PCR in peripheral blood leukocytes of above-mentioned cases and the results were verified by direct DNA sequencing method.Results The frequencies of -308G/A(GA),-308G/A(AA),-C34G(CG)and-C34G(GG)were 24.00%,26.67%,24.00% and 26.00% in MAP group,34.67%,36.67%,34.00% and 36.67% in MSAP group,42.00%,46.00%,43.33% and 46.00% in SAP group,and 14.44%,14.22%,12.89% and 14.67% in control group,respectively.Statistical tests showed significant difference in the frequencies among each group (all P1). Conclusion These carriers of-308G/A(GA),-308G/A(AA),-C34G(CG)and-C34G(GG)genotypes may have a high risk of developing AP,and significant interactions between genetic polymorphisms of-308G/A and-C34G add the risk of the occurrence and development of AP.

Echinococcus granulosus stimulates high PPARα/γ expression and drives polarization of macrophages in vitro / 中国免疫学杂志

Objective:To investigate the expression levels of PPARα/γin RAW264. 7 cells in the early stages of co-cultivation with Echinococcus granulosus in vitro. Methods:RAW264. 7 cells were co-cultured with E. granulosus and collected at 12,24,36,48, 72 h. The mRNA levels of PPAR-γ,PPAR-α,M1 macrophages-associated cytokines including TNF-α,MCP-1 and IL-1β,and M2 mac-rophages-associated cytokines including Arg-1,TGF-β and Fizz-1 were detected by qRT-PCR. The protein levels of Arg-1 and MR were analyzed by ELISA. Results:The expression levels of PPAR-γ, PPAR-αand the M2 macrophages-associated cytokines including Arg-1,TGF-β,Fizz-1 and MR were significantly increased,especially at 72 h (P<0. 05). M1 macrophages-associated cytokines including TNF-α,MCP-1 and IL-1β were decreased at 72h although increased at first. Conclusion:During the early stages of co-cultivation with Echinococcus granulosus in vitro, the levels of PPAR-γ/α are up-regulated in RAW264. 7 cells, which may drive macrophage polarization and play a role in the immune escape.

Galangin Suppresses Pro-Inflammatory Gene Expression in Polyinosinic-Polycytidylic Acid-Stimulated Microglial Cells

Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-κB activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-γ, known to play an anti-inflammatory role. To investigate whether PPAR-γ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-γ antagonist before treatment of galangin. We found that PPAR-γ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-α and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-κB, and PPAR-γ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.

Galangin Suppresses Pro-Inflammatory Gene Expression in Polyinosinic-Polycytidylic Acid-Stimulated Microglial Cells

Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-κB activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-γ, known to play an anti-inflammatory role. To investigate whether PPAR-γ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-γ antagonist before treatment of galangin. We found that PPAR-γ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-α and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-κB, and PPAR-γ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.

Peroxisome Proliferator-activated Receptor-gamma Inhibits the Activation of STAT3 in Cerulein-stimulated Pancreatic Acinar Cells

Cerulein-induced pancreatitis is similar to human edematous pancreatitis, characterized by the dysregulation of digestive enzyme production, edema formation, and an infiltration of inflammatory cells into the pancreas. We previously showed that the Janus kinase 2 (JAK2)/STAT3 pathway mediates inflammatory signaling in cerulein-stimulated pancreatic acinar cells. PPAR-γ has been implicated in the regulation of inflammatory responses in several cells. In the present study, we investigated the role of PPAR-γ in cerulein-induced activation of JAK2/STAT3 in pancreatic acinar cells. Treatment with cerulein induced the activation of JAK2/STAT3 and PPAR-γ expression in AR42J cells. Cerulein-induced PPAR-γ expression was inhibited by AG490, a JAK2/STAT3 inhibitor, in AR42J cells. An immunoprecipitation analysis showed that PPAR-γ binds to STAT3 in cerulein-stimulated AR42J cells. Down-regulation of PPAR-γ by siRNA increased STAT3 phosphorylation in AR42J cells stimulated with cerulein. These results show that PPAR-γ inactivates STAT3 by directly interacting with STAT3 in cerulein-stimulated pancreatic acinar cells. Overexpression of PPAR-γ may be beneficial for preventing pancreatitis by suppressing the activation of STAT3 in pancreatic acinar cells.

Effects of total flavonoids of litchi and rosiglitazone on expression of PPAR-γ and CTGF in HSC-T6 rat hepatic stellate cells / 实用医学杂志

Objective To investigate effects of total flavonoids of litchi (TFL) on the proliferation of rat hepatic stellate cells (HSC-T6) in comparison with western medicine rosiglitazone, and to explore the mechanism of anti hepatic fibrosis of TFL. Methods Effect of TFL on proliferation of HSC-T6 was examined by MTT. The expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) mRNA, connective tissue growth factor (CTGF) mRNA in HSC-T6 cells exposured were examined by real-time quantitative PCR. Effects on HSC-T6 CTGF protein from TFL and rosiglitazone were detected by Western bloting. Results The expression of PPAR-γ mRNA was upregulated and the expression of CTGF mRNA and protein was downregulated after exposure to TFL and rosiglitazone for 72 hours. And the effect of TFL increased with the increase of concentration. Conclusion TFL can inhibit the proliferation of HSC-T6 and antagonizing liver fibrosis. This mechanism may be associated with the upregulation of PPAR-γ expression and the downregulation of CTGF expression.

Effect of hawthorn proanthocyanidins and vitimin C on liver oxidative stress in insulin-resistance rats / 中草药

Objective: To explore the effect of hawthorn proanthocyanidins (HPC) and vitimin C (VC) on liver oxidative stress in insulin-resistance rats. Methods: The insulin-resistance models were prepared by high-fat diet, the weight variations of all rats were tested before and after modeling, so were the contents of fasting blood-glucose and serum insulin after modeling. The colorimetric technique was used to test the concentration of serum ALT, AST, and ALP. The rats in high-fat diet group, who were succeeded in modeling, were divided into model, HPC (56 g/kg), VC (180 g/kg), HPC (56 g/kg) + VC (180 g/kg), and rosiglitazone (122 g/kg) groups. After 12 weeks of continuous administration, these indexes, such as levels of SOD, CAT, GSH-Px, GSH, and MDA in liver homogenates and SOD, GSH-Px, Na+, K+-ATPase, Ca2+, Mg2+-ATPase, and MDA in liver mitochondria, were all tested; RT-PCR was used to test the expression of PPAR-γ mRNA; The Western blotting method was adopted to test the PPAR-γ protein expression. Results: After modeling, the body weight of rats decreased significantly (P<0.05), the concentration of blood, such as glucose, serum insulin ALT, AST, and ALP all increased significantly (P<0.01); The model group was compared with control group, the activities of SOD, CAT, GSH-Px, and GSH were significantly decreased (P<0.01), the levels of glucose, insulin, and MDA increased significantly (P<0.01) in rat liver homogenate, the activities of SOD, GSH-Px, Na+, K+-ATPase, and Ca2+, Mg2+-ATPase were significantly decreased (P<0.01) and MDA level increased significantly (P<0.01) in the liver mitochondria; PPAR-γ mRNA and protein expression decreased significantly in liver tissue (P<0.01). HPC, VC, HPC + VC, and rosiglitazone improved the above indexes, which in the HPC + VC group was better than that in the HPC group and VC group, equivalent to that in rosiglitazone group. Conclusion: Liver oxidative stress which is resulted from insulin-resistance can be improved when HPC and VC are combined.

Peroxisome proliferator-activated receptor-γ agonist pioglitazone fails to attenuate renal fibrosis caused by unilateral ureteral obstruction in mice / 华中科技大学学报（医学）（英德文版）

Renal tubulointerstitial fibrosis is the common ending of progressive renal disease. It is worth developing new ways to stop the progress of renal fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been studied to treat diabetic nephropathy, cisplatin-induced acute renal injury, ischemia reperfusion injury and adriamycin nephropathy. In this study, unilateral ureteral obstruction (UUO) was used to establish a different renal fibrosis model. PPAR? agonist pioglitazone was administrated by oral gavage and saline was used as control. At 7th and 14th day after the operation, mice were sacrificed for fibrosis test and T lymphocytes subsets test. Unexpectedly, through MASSON staining, immunohistochemistry for α-SMA, and Western blotting for a-SMA and PDGFR-β, we found that pioglitazone failed to attenuate renal fibrosis in UUO mice. However, flow cytometry showed that pioglitazone down-regulated Th1 cells, and up-regulated Th2 cells, Th17 cells and Treg cells. But the Th17/Treg ratio had no significant change by pioglitazone. Real-time PCR results showed that TGF-β and MCP-1 had no significant changes, at the same time, CD4(+) T cells associated cytokines were partially regulated by pioglitazone pretreatment. Taken together, pioglitazone failed to suppress renal fibrosis progression caused by UUO.