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Effects of curcumin on peroxisome proliferator-activated receptor γ expression and nuclear translocation/redistribution in culture-activated rat hepatic stellate cells

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Chinese Medical Journal 2007年第9期120卷 794-801页

作者： CHENG Yang PING Jian XU Lie-ming Institute of Liver Diseases Shuguang Hospital Shanghai University of TCM Shanghai 201203 China

Background The function of peroxisome proliferator-activated receptor γ （PPARγ） in hepatic fibrogenesis remains largely unknown. Curcumin is a natural substance extracted form Curcuma Longa Linn and has a variety of pharmacological effects. In this study, the effects of curcumin on the proliferation, activation and apoptosis of rat hepatic stellate cells （HSCs） through PPARγ signaling were investigated. Methods HSCs were isolated from the normal Sprague Dawley rats through in situ peffusion of the liver with Pronase E and density-gradient centrifugation with Nycodenz. Cells were treated with curcumin, troglitazone, salvianolic acid B or GW9662. The effect on HSCs proliferation was determined by MTT colorimetry. Total RNA was extracted by TRizol reagent and gene levels were determined by semi-quantitative RT-PCR. Total cellular and nuclear protein were isolated and separated by 10% sodium dodecy Isulfate polyacrylamide gel electrophoresis. Protein levels were determined by Western blot. Cell apoptosis was detected by Hoechst 33258 staining. PPARγ subcellular distribution was detected by immunofluorescent staining. The activities of MMP-2 and 9 were measured by Gelatin zymograph assay. Results Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARγ nuclear expression level decreased. Curcumin up-regulated PPARγ expression and significantly inhibited the production of a-SMA and collagen Ⅰ. PPARγ is expressed in the cytoplasm and nucleus and is evenly distributed in HSCs, but accumulated in the nucleus of HSCs and disappeared from cytoplasm after curcumin treatment. Hoechst 33258 staining showed that curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFKB p65 protein and TGFβR-Ⅰ protein expression were down-regulated significantly by curcumin. The acti

关键词： curcumin hepatic stellate cell peroxisome proliferator-activated receptor γ

Effect of ligand troglitazone on peroxisome proliferator-activated receptor γ expression and cellular growth in human colon cancer cells

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World Journal of Gastroenterology 2006年第45期12卷 7263-7270页

作者： Mei Ming Jie-Ping Yu Xiang-Zhi Meng Yan-Hong Zhou Hong-Gang Yu He-Sheng kuo Department of Gastroenterology Renmin Hospital of Wuhan University Wuhan 430060 Hubei Province China Department of Pathophysiology and Pathology Medical College of Wuhan University Wuhan 430071 Hubei Province China

AIM： To investigate the effect of troglitazone on peroxisome proliferator-activated receptor γ （PPARγ） expression and cellular growth in human colon cancer HCT-116 and HCT-15 cells and to explore the related molecular mechanism.METHODS： Human colon cancer HCT-116 and HCT-15 cells cultured in vitro were treated with troglitazone. Reverse transcription-polymerase chain reaction （RT-PCR） and Western blot were employed to detect the effect of troglitazone on PPARy expression. The proliferative activity was determined by MTT assay, cell cycle and apoptosis were detected by flow cytometry. Apoptosisrelated genes, cell cycle regulatory genes and p53 were examined by RT-PCR and Western blot respectively. RESULTS： The expression of PPARy in colon cancer HCT-116 and HCT-15 cells was up-regulated by troglitazone. Troglitazone inhibited proliferation, induced apoptosis and cell cycle G1 arrest in colon cancer cells. Troglitazone induced p53 expression in HCT-116 cells, but not in HCT-15 cells. The down-regulation of survivin and bcl-2 was found in both cell lines and up-regulation of bax was found only in HCT-116 cells, being consistent with growth inhibition in HCT-116 cells but not in HCT-15 cells. Troglitazone increased expression of p21^WAF1/CIP1 （p21）, p27^KIP1 （p27） and reduced cyclin D1 in HCT-116 cells while only a minor decrease of cyclin D1 was found in HCT-15 cells. CONCLUSION： Troglitazone is an inductor of PPARγ in colon cancer cells and inhibits PPARγ-dependently proliferation, which may attribute to cell cycle G1 arrest and apoptosis in colon cancer cells. Troglitazone may induce p53-independent apoptosis and p53- dependent expression of p21 and p27. Depending on cell background, different activation pathways may exist in colon cancer cells.

关键词： peroxisome proliferator-activated receptor γ Colon cancer Troglitazone Cellular growth Cell cycle Apoptosis

Troglitazone, a peroxisome proliferator-activated receptor γ ligand, induces growth inhibition and apoptosis of HepG2 human liver cancer cells

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World Journal of Gastroenterology 2008年第14期14卷 2168-2173页

作者： Yan-Ming Zhou Yin-Hao Wen Xiao-Yan Kang Hai-Hua Qian Jia-Mei Yang Zheng-Feng Yin Department of Molecular Oncology Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China

AIM: To examine the effect of troglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) ligand, on the proliferation and apoptosis of human liver cancer cells. METHODS: Liver cancer cell line HepG2 was cultured and treated with troglitazone. Cell proliferation was detected by 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferase- mediated nick end labeling of DNA fragmentation sites (TUNEL) assay; and apoptosis-related protein was detected by immunocytochemistry and Western blotting. RESULTS: Troglitazone inhibited growth and induced apoptosis of HepG2 cells in a dose-dependent manner, and induced activation of caspase-3 expression. Troglitazone not only drove apoptosis-inhibiting factor survivin to translocate incompletely from the nucleus to the cytoplasm, but also inhibited expression of survivin, while it did not affect expression of apoptosis-promoting factor Bax. CONCLUSION: PPARγ ligands inhibit growth and induce apoptosis of liver cancer cells, and may have applications for the prevention and treatment of liver cancer.

关键词： peroxisome proliferator-activated receptor γ Troglitazone Liver neoplasms Apoptosis

Expression for peroxisome proliferator-activated receptor gamma in pituitary adenomas 38 cases for semi-quantitative immunohistochemical analysis

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Neural Regeneration Research 2008年第7期3卷 756-759页

作者： Xiaojie Lu Kailai Chen Weiyang Ji Qing Wang Bing Li Jiang＇an Li Jiyong Sun Department of Neurosurgery Wuxi Second Hospital Affiliated to Nanjing Medical University Wuxi 214002 Jiangsu Province China

BACKGROUND： It has been reported that peroxisome proliferator-activated receptor γ （PPAR γ ） is highly expressed in lung cancer, colon cancer, and gastric cancer, as well as other tumors.OBJECTIVE： To study expression of PPAR γ in pituitary adenomas and analyze the role of PPAR γ in hormonal typing of pituitary adenomas. DESIGN, TIME AND SETTING： Semi-quantitative immunohistochemistry of pathological specimens. The experiment was conducted at the Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University between January 2002 and May 2005. MATERIALS： Surgical resection samples of pituitary adenomas from 38 cases （18 male and 20 female） were analyzed. Eight cases were determined to be invasive pituitary adenomas and 30 cases were non-invasive pituitary adenomas. Hormonal classification of the types of pituitary adenomas revealed somatotrophic adenomas in six cases, corticotrophic adenoma in five cases, prolactinomas in 13 cases, multi-hormone secreting adenomas in six cases, and eight cases of adenoma without altered endocrine function. Five autopsy specimens were collected during the same period from patients of matching age that died from unrelated diseases and were included as normal anterior pituitar3, controls. METHODS： Cell counts for positive immunohistochemical signals were recorded from histopathological sections. The percentage of positive cells was reported as a semi-quantitative analysis. MAIN OUTCOME MEASURES： The rate of PPAR γ positive cells in different types of adenoma was based on hormonal levels and invasiveness of pituitary tumor cells. RESULTS： All tumor biopsies were determined to express PPAR γ. The rate of PPAR γ -positive cells ranged between 8%-65% in the pituitary adenomas. According to hormonal type, PPAR γ expression did not vary between the groups. In addition, there was no significant difference in PPAR γ expression between the non-invasive and invasive pituitary adenomas. CONCLUSIONS： Human p

关键词： peroxisome proliferator-activated receptor γ pituitary adenomas immunohistochemistry

Association between Cardiac Changes and Stress, and the Effect of peroxisome proliferator-activated receptor-γ on Stress-induced Myocardial Injury in Mice

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2015年第1期35卷 28-34页

作者：高进辽薛桥王士雯高丽菲蓝云锋方舟傅义程刘岩李泱范利 First Department of Geriatric Cardiology Chinese PLA General Hospital Department of Cardiology Chinese PLA General Hospital Outpatient Department Jingxi Hospital of The Military General Hospital of Beijing PLA

This study was aimed to investigate the effect of stress induced by high-intensity exercises on the cardiovascular system. In the epidemiological investigation, 200 subjects（test group） engaged in special high-intensity exercises, and 97 who lived and worked in the same environment and conditions as those in the test group, but did not participate in the exercises served as controls. In the second part of the study, 50 mice were randomly divided into control group, exhaustive swimming group, white noise group, exhaustive swimming plus white noise group, and pioglitazone intervention group. The results showed that the plasma concentrations of the myocardial injury markers heart fatty acid-binding protein（H-FABP）, C-reactive protein（CRP）, β-endorphin（β-EP） and levels of psychological stress were significantly increased in test group as compared with control group; special high-intensity exercises resulted in a significant elevation of the incidence of cardiac arrhythmias. Animal experiments showed that the plasma levels of corticosterone（CORT） and troponin I（Tn I） were raised while the level of SOD was reduced in exhaustive swimming group, white noise group, and exhaustive swimming plus white noise group. The expression levels of PPARγ m RNA and protein were decreased in myocardial tissues in these groups as well. HE staining showed no remarkable change in myocardial tissues in all the groups. Treatment with pioglitazone significantly decreased the plasma levels of Tn I and CORT, while increased the level of SOD and the expression levels of PPARγ m RNA and protein. It was concluded that the high-intensity exercises may induce a heavy physical and psychological stress and predispose the subjects to accumulated fatigue and sleep deprivation; high-intensity exercises also increases the incidence of arrhythmias and myocardial injury. PPARγ may be involved in the physical and psychological changes induced by high-intensity exercises.

关键词： stress cardiovascular disease peroxisome proliferator-activated receptor γ human mice

Antifibrotic Effect of Total Flavonoids of Astmgali Radix on Dimethylnitrosamine-lnduced Liver Cirrhosis in Rats

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Chinese Journal of Integrative Medicine 2017年第1期23卷 48-54页

作者： CHENG Yang MAI Jing-yin WANG Mei-feng CHEN Gao-feng PING Jian Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai 201203China Shanghai Pudong New Area Hospital of Traditional Chinese Medicine Shanghai 201299China

Objective：To study the effect of total flavonoids of Astmgali Radix（TFA）on liver cirrhosis induced with dimethylnitrosamine（DMN）in rats,and the effect on peroxisome proliferator-activated receptorγ（PPARγ）,uncoupling protein 2（UCP2）and farnesoid X receptor（FXR）.Methods：Fifty-three Sprague-Dawley rats were randomly divided into a control group（10 rats）and a DMN group（43 rats）.Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group（14 rats）,a low-dosage TFA group（14 rats）and a high-dosage TFA group（15 rats）in the 3rd *** were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low-and high-TFA groups,*** the end of the experiment blood and liver samples were *** liver function and liver tissue hydroxyproline content were ***-eosin（HE）,Sirus red and immunohistochemical stainings of collagenⅠ,smooth muscle actin（α-SMA）was conducted in paraffinembedded liver tissue *** time polymerase chain reaction（PCR）was adopted to determine PPARγ,UCP2 and FXR m RNA *** blot was adopted to determine protein levels of collagenⅠ,α-SMA,PPARγ,UCP2 and ***：Compared with the model group,TFA increased the ratio of liver/body weight（low-TFA group P〈0.05,high-TFA group P〈0.01）,improved liver biochemical indices（P〈0.01 for ALT,AST,GGT in both groups,P〈0.05 for albumin and TBil in the high-TFA group）and reduced liver tissue hydroxproline content（P〈0.01 in both groups）in treatment groups *** staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition,alleviated formation and extent of liver ***Ⅰandα-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model *** could increase PPARγ,it regulated target UCP2,and FXR levels significantly compared with the model group（in the low-TFA group all P〈0.05,in t

关键词： total flavonoids of Astmgali Radix dimethylnitrosamine liver cirrhosis peroxisome proliferator-activated receptor γ uncoupling protein 2 farnesoid X receptor rat

Troglitazone induced apoptosis of human pterygium fibroblasts through a mitochondrial-dependent pathway

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International Journal of Ophthalmology(English edition) 2011年第2期4卷 143-146页

作者： Xiao-Xi Yang, Jin-Tang Xu Department of Ophthalmology the First Affiliated Hospital of Jinan University Guangzhou 510632 Guangdong Province China Laboratory of Ophthalmology School of Medicine Jinan University Guangzhou 510632 Guangdong Province China

AIM: To study the effect of troglitazone on primary culture human pterygium fibroblast (HPF). METHODS: Cell viability loss and apoptosis were quantified by cell counting kit-8, AnnexinV-FITC/PI double staining, caspases activity test and western blotting. Flow cytonnetry was used to detect mitochondrial membrane potential. RESULTS: peroxisome proliferator-activated receptor gamma (PPAR-gamma) was positively expressed in pterygium specimens (n = 5). Troglitazone showed dose-dependent inhibition of cell survival, induced phospholipids redistribution, activated caspase-3, -9, and altered mitochondrial potential. Western blot assay demonstrated the increase of Bax/Bcl-2 protein ratio. CONCLUSION: Troglitazone induced apoptosis of HPF through a mitochondrial-dependent pathway.

关键词： pterygium peroxisome proliferator-activated receptor γ troglitazone apoptosis

An experimental study of pioglitazone in treating vascular dementia

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Journal of Pharmaceutical Analysis 2010年第3期22卷 179-182页

作者： Lu Gao1,Ting Wei2,Yuan-yuan Lu2,Li Wang3(1.Emergency Department,the First Affiliated Hospital,Medical School of Xi’an Jiaotong University,Xi’an 710061 2.Department of Internal Medicine,Hospital of Xi’an Jiaotong University,Xi’an 710049 3.Medical School of Xi’an Jiaotong University,Xi’an 710061,China) Emergency Department First Affiliated Hospital Medical School of Xi'an Jiaotong University Xi'an 710061 China Department of Internal Medicine Hospital of Xi'an Jiaotong University Xi'an 710049 China Medical School of Xi'an Jiaotong University Xi'an 710061 China

Objective To compare the therapeutic effects of different doses of pioglitazone,a kind of peroxisome proliferator-activated receptor γ(PPARγ)agonist,on vascular dementia and explore how pioglitazone affects cerebral *** Modified Pulsinelli’s vessel ligation was used to establish a vascular dementia model in ***,learning and memory were evaluated by Morris’s water maze *** staining was used to determine the number of nerve *** double-staining was used to examine the expression of PPARγ/nerve cells and PPARγ/astrocytes in different *** Both in pioglitazone groups and sham-operation group,the latency was reduced significantly compared to that in control group(P<0.01).Sham-operation group had the largest number of neurons in the cortex,followed by low-dose pioglitazone group and high-dose pioglitazone group,and control group came *** with control group,pioglitazone groups had more PPARγ expression in nerve cells,and the fluorescence intensity of PPARγ was *** Pioglitazone can induce the expression of PPARγ in neuron endochylema and astrocyte endochylema to protect nerve cells,and then to improve spatial learning and memory function in VD rats.

关键词： vascular dementia pioglitazone peroxisome proliferator-activated receptor γ immunoenzyme staining immunofluorescence

Swietenia mahagony extract shows agonistic activity to PPAR7 and gives ameliorative effects on diabetic db/db mice

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Acta Pharmacologica Sinica 2005年第2期 220-222页

作者： Dan-dan LI~(1,2,5),Jun-hua CHEN~(1,4,5),Qing CHEN~(1,4),Guo-wei LI~(1,4),Jing CHEN~(1,4),Jian-min YUE~(1,4),Min-li CHEN~3,Xiao-ping WANG~2,Jian-hua SHEN~(1,4,6),Xu SHEN~(1,4,6),Hua-liang JIANG~(1,4,6)~1Drug Discovery and Design Center,State Key Lab of Drug Research,Shanghai Institute of Materia Medica,Shanghai Institutes for BiologicalSciences,Chinese Academy of Sciences,Shanghai 201203,~2Chemistry Department,Tongji University,Shanghai 200092,~3Animal Experi-ment Center,Zhejiang College of Traditional Chinese Medicine,Hangzhou 310053 ~4Graduate School of the Chinese Academy of Sciences,China

Aim:To search the peroxisome proliferator-activated receptor γ(PPARγ)agonistsfrom Swietenia mahagony extract(SmE)and observe the possible ameliorativeeffects of SmE on diabetic db/db ***:The PPARγagonistic activity ofSmE was screened by yeast-two hybrid *** blood glucose levels ofdiabetic db/db mice were measured using a blood glucose level monitor and thedata were statistically analyzed by NDST8.8W ***:By using theclinical drug rosiglitazone as a positive control,it was found that the PPARγagonistic activity of SmE at a concentration of 50μg/L was approximately half thatof 35.7μg/L(0.1μmol/L)of *** the dose of 1000 mg/kg,SmE remark-ably decreased the blood glucose concentration of db/db mice from(15.26±2.98)to(7.58±2.20)mmol/L,and reduced the blood glucose levels by 55.49% comparedwith the control group(P<0.01).Conclusion:SmE shows agonistic activity toPPARγ and can ameliorate the blood glucose levels of diabetic db/db *** be thus used as a potential agent for diabetes therapy.

关键词： Swietenia mahagony diabetes mellitus peroxisome proliferator-activated receptor γ yeast-two hybrid