Effect of epigallocatechin-3 gallate on cholesterol efflux in foam cells and its mechanism / 中华老年心脑血管病杂志

Objective To study the effect of epigallocatechin-3 gallate (EGCG) on cholesterol efflux in foam cells and its mechanism.Methods THP-1 cells were induced to differentiate into macrophages which were then transformed to foam cells.Foam cells were divided into 0 μmol/L EGCG group,10 μmol/L EGCG group,30 μmol/L EGCG group,and 100 μmol/L EGCG group (1.5 × 106 in each group).Their cholesterol content was measured with a cholesterol test kit,apoA-I-mediated cholesterol efflux was assayed with a liquid scintillation counter,expression of ATP-binding cassette A1 (ABCA1) was detected by RT-PCR and Western blot respectively.Results The ABCA1 mRNA and protein expression levels and cholesterol efflux were significantly higher while the cholesterol content was significantly lower in 10 μmol/L EGCG group,30 μmol/L EGCG group,and 100 μmol/L EGCG group than in 0 μmol/L EGCG group (7.04％ ±0.21％,7.75％±0.17％ and 8.53％±0.18％ vs 3.37％±0.16％,P＜0.01;419.33±19.75 mg/g,352.58± 14.23 mg/g and 312.62±17.45 mg/g vs 520.51 ±20.62 mg/g,P＜0.01),and in 30 μmol/L EGCG group,100μmol/L EGCG group than in 10μmol/L EGCG group (P＜0.05).Conclusion EGCG increases cholesterol efflux and decreases cholesterol content in foam cells by upregulating the transcription and expression of ABCA1.

Inhibitory effect of epigallocatechin-3-gallate on the proliferation of hepatic carcinoma cells / 解放军医学杂志

Objective To study the effect of epigallocatechin-3-gallate (EGCG) on the proliferation and apoptosis of hepatic carcinoma HepG2 cells, and to explore the possible mechanism. Methods HepG2 cells were treated with EGCG in various concentrations (0, 25, 50, 100, 200, 400mg/L) for 24, 48 and 72h, and then the cell proliferation inhibition rate was determined with MTT. Again, the HepG2 cells were treated with various concentrations of EGCG (0, 50, 100, 200mg/L) for 24h, and then the cell apoptosis rate, cell cycle, and the expressions of cell division cycle protein 25A (CDC25A), and Smad3 protein were determined with flow cytometry. mRNA expressions of CDC25A and Smad3 were assessed with RT-PCR. Results The results of MTT showed that various concentrations of EGCG inhibited the growth of HepG2 cells in dose and time dependent manner (P<0.01). The result of flow cytometry showed that, with the increase of of EGCG concentration, the cell proliferation index (PI) decreased significantly (P<0.01), while the apoptosis rate increased obviously (P<0.01); the expression levels of CDC25A protein and mRNA decreased (P<0.05) and of Smad3 protein and mRNA increased (P<0.05). Conclusion EGCG may play a role in growth inhibition of hepatic carcinoma cells by down-regulating the expression of CDC25A, up-regulating the expression of Smad3, thus inhibiting proliferation and inducing apoptosis of HepG2 cells.

Effect of epigallocatechin gallate and fructus psoraleae on the induction of vitiligo-like depigmentation by monobenzone in mice / 中华皮肤科杂志

Objective To study the effect of epigallocatechin gallate (EGCG) and fructus psoraleae on the induction of vitiligo-like depigmentation by monobenzone in mice.Methods Forty C57BL/6 mice were included in this study.Hairs in an area measuring 2 cm × 2 cm in size were shaved on the back of each of these mice.Then,the mice were randomly and equally divided into four groups to be topically treated with vaseline cream (negative control group),monobenzone 40％ cream (model group),EGCG 5％ cream followed by monobenzone 40％ cream (EGCG group),fructus psoraleae 7％ cream followed by monobenzone 40％ cream (fructus psoraleae group),on the shaved area,respectively,for 50 consecutive days.Depigmentation of skin and hairs was observed daily by naked eyes for 15 days after drug withdrawal.At the end of the study,all the mice were sacrificed,and skin specimens were resected from the tested regions in them.Hematoxylin and eosin (HE) staining was performed to observe lymphocyte infiltration,and immunofluorescence assay to estimate the frequency of CD8 + T cells.Results Depigmentation was observed in monobenzone-induced and-uninduced sites in the model group,and in monobenzone-induced sites in all the mice in the EGCG group and fructus psoraleae group,but in neither monobenzone-induced nor-uninduced sites ih the negative control group.The average time for the appearance of depigmentation at monobenzone-induced sites was 16.7,29.3 and 19.9 days in the model group,EGCG group and fructus psoraleae group respectively.The depigmentation area index at monobenzone-induced sites was 4.00 ± 0.00 in the model group,significantly different from that in the EGCG group and fructus psoraleae group (2.11 ± 0.54 and 2.84 ± 0.79,both P ＜ 0.05).Significant differences were also observed in depigmentation area index at monobenzone-induced sites among the model group,EGCG group and fructus psoraleae group (F =14.173,P ＜ 0.05),and at monobenzone-uninduced sites between fructus psoraleae group and EGCG group (P ＜ 0.05).The frequency (expressed as fluorescence intensity) of CD8+ T cells was significantly lower in the EGCG group and fructus psoraleae group than in the model group,and significantly different between EGCG group and fructus psoraleae group (P ＜ 0.05).Conclusions Both EGCG and fructus psoraleae,especially EGCG,can interfere with the induction of vitiligo-like depigmentation of skin and hairs by monobenzone in mice.The mouse model of vitiligolike depigmentaion in this study shows higher similarity to human vitiligo.

Rational use of antioxidants in solid oral pharmaceutical preparations

Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations.

Atualmente, antioxidantes são usados como excipientes eficientes, que retardam ou inibem o processo de oxidação de moléculas. Excipientes são frequentemente associados a efeitos adversos. Estudos de estabilidade podem ajudar na busca por possíveis soluções para minimizar ou retardar os processos de degradação. A habilidade de prever as reações de oxidação em diferentes fármacos é importante. O estudo foi conduzido com o objetivo de avaliar o uso racional de hidroxianisol butilado (BHA), hidroxitolueno butilado (BHT), metabissulfito sódico (SMB), galato de propila (PG) e cisteína (CYS) em formulações de comprimidos de sinvastatina e cetoconazol. Eles foram avaliados por parâmetros de estabilidade e pela relação entre a eficiência dos antioxidantes e a estrutura química do fármaco. Os resultados foram comparados com testes de DPPH e simulações em computador. BHT foi mais eficiente com relação a estabilidade da sinvastatina e às concentrações mais eficientes para manutenção de estabilidade foram 0,5 e 0,1%. Com relação ao cetoconazol, SMB foi mais eficiente em manter o conteúdo e o perfil de dissolução. A avaliação por DPPH mostrou que o maior percentual de redução de absorção foi observado para PG, enquanto que SMB mostrou ser mais eficiente e consumir menos DPPH. A mesma tendência foi observada com menos eficiência em todos os outros antioxidantes lipofílicos como o BHT e BHA. Os resultados do estudo de modelagem molecular demonstraram que as propriedades eletrônicas obtidas podem ser correlacionadas com a atividade antioxidante em solução, sendo útil para o desenvolvimento racional de formulações farmacêuticas líquidas, mas não para formulações sólidas orais. Este estudo demonstrou a importância de considerar parâmetros de estabilidade e modelagem molecular para elucidar os fenômenos químicos envolvidos na atividade antioxidante, sendo úteis para o uso racional de antioxidantes no desenvolvimento de formulações farmacêuticas.

Effects and mechanism of EGCG on human prostate cancer xenografted tumor growth and connexin43 expression in nude mice / 中国医师杂志

Objective To observe the effects of ( - )-epigallocatechin-3-gallate (EGCG) on human prostate cancer xenografted tumor growth and connexin43 expression in nude mice,and explore the mechanism of the EGCG on prevention for prostate cancer.Methods The methyl thiazolyl tetrazolium and annexin-V/PI double-labeled flow cytometry methods were used to observe the growth inhibiting rate (IR)and apoptosis rate (AR) of human prostate cancer cell line PC-3 which was treated by EGCG at different concentration (10,20 and 40 mg/L,respectively).The scrape-loading fluorescence dye transfer method was applied to assess the gap junction intercellular communication (GJIC) through fluorescence microscope.PC-3 cells were subcutaneously transplanted to establish tumor-bearing nude mice model.A total of 32 mice were randomly divided into four groups,both control group and three treatment groups were treated with different doses of EGCG ( 10,20 and 40 mg/kg,respectively).After two weeks,the mice prostate tumor tissues were taken out.The tumor wet weight was measured and tumor growth inhibiting rate was calculated.The tumor microvascular density (MVD) and apoptosis index (AI) were detected by the immunohistochemical techniques and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling techniques,respectively.Semi-quantitative reverse transcription polymerase chain reaction was used to examine the expression level of the Cx43 mRNA.Results EGCG at concentration ( 10 and 20 mg/L) could significantly inhibit the proliferation[(22.33 ±4.62)％,(38.67 ±5.67)％ vs (3.47 ±0.31 )％,P ＜0.01],induce the apoptosis [(7.84 ± 1.37 ) ％,( 24.53 ± 2.28 ) ％ vs ( 2.17 ± 0.70 ) ％,P ＜ 0.01] and enhance the GJIC of PC-3 cells.EGCG of different doses could inhibit prostate cancer xenografted tumor growth,induce tumor cells apoptosis and inhibit angiogenesis.EGCG ( 20 and 40 mg/kg) could effectively up-regulate Cx43 mRNA expression in xenografted tumor (0.58 ± 0.08,0.80 ± 0.07 vs 0.42 ± 0.04,P ＜ 0.0 ).The effects had significant correlation with the dose-dependent of EGCG ( P ＜ 0.05 ).Conclusions EGCG could up-regulate the Cx43 expression and enhance the gap junction intercellular communication mediated by Cx43 in the prostate tumor,which provide the experimental evidence for the mechanism of its effectively inhibiting the prostate cancer growth.

Synthesis, characterization and evaluation of antibacterial and antifungal activity of triazole derivatives of gallic acid.

Heterocycles bearing a symmetrical triazole represent an interesting class of compounds possessing a wide spectrum of biological activities such as antiinflammatory, anticancer, antitubercular, antiviral and antimicrobial properties. In present study an attempt was made to synthesize compounds using propyl gallate and hydrazine hydrate as starting material. And following the scheme five different compounds using different aromatic substituents. Synthesized compounds were subjected to physical characterization and spectral analysis for structural confirmation. The compounds were than subjected to evaluation of antibacterial and antifungal activity. The bacterial screening indicated that among the test compounds number S2, S3, moderately activity against all the tested bacterial strains Bacillus subtilus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae. The remaining compounds were found to be less active. Minimum inhibitory concentration value of the compounds against the bacteria stains reveals that compound S3, S4 have better onset of action against all bacteria strains as compared to that of standard. Antifungal screening revealed that the test compounds showed moderate activity against Aspergillus niger.

Effect of propyl gallate on cyclooxygenase-1/-2 activity,mRNA and protein expression in murine macrophages / 中国药理学通报

0.05),but enhanced 6-keto-PGF_(1?) synthesis at concentrations of 1,0.5,0.1 and 0.01 ?mol?L~(-1)(P

A Case of Allergic Contact Cheilitis from Propyl Gallate / 대한피부과학회지

Propyl gallste and other gallic acid esters are used as antioxidants in lipsticks, lip balms and salves, cosmetic creams and lotions, bakery products, edible fats and other pharmaceutical and industrial products. Propyl gallate is used widely but allergic contact dermatits from propyl gallate is rare. A 44-year-old female patient had pruritic multiple tiny erythematous papules and vesicles on the margin of her lip for a week. We found that the causative material of the allergic contact cheilitis was propyl gallate. We proved it with a patch test, provocation use test and quantitative and qualitative analysis of the lipstick. To our knowledge, this is the first case report of lipstick allergic contact cheilitis from propyl gallate in Korean literature.