Cardioprotective and hepatoprotective effects of Citrus hystrix peels extract on rats model

Objective:To observe the combination effect of doxorubicin and Citrus hystrix(kaffir lime's)peel ethanolic extract(ChEE)on blood serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activity and cardio-hepato-histopathology of female Sprague Dawley rats.Methods:Doxorubicin and ChEE(5 rats per group)were administered in five groups of 3 rats each for 11 d.Group I:doxorubicin(dox)4.67 mg/kg body weight;Group II:dox+ChEE 500 mg/kg body weight;Group HI:dox+ChEE 1000 mg/kg body weight;Group IV:ChEE 1000 mg/kg body weight;Group V:untreated(control).Results:ChEE repaired cardiohistopathology profile of doxorubicin induced cardiotoxicity and hepatotoxicity rats,but did not repair neither hepatohistopathology profile nor reduce serum activity of ALT and AST.Conclusion:ChEE has potency to be developed as cardioprotector agent in chemotherapy.

Targets and molecular mechanisms of a citrus flavonoid, hesperidin, against luminal breast cancer cells: an integrative bioinformatics analysis

Objective:To identify the potential target and mechanisms of hesperidin in MCF-7 estrogen receptor-positive breast cancer cells using bioinformatics approaches.Methods:Gene expression profiles were accessed from public database GSE85871.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was carried out with Database for Annotation,Visualization and Integrated Discovery.The protein-protein interaction network was analyzed by STRING-DB and visualized by Cytoscape.Transcription factor regulatory networks were constructed from TRED,TRRUST,Reg Network and visualized by Cytoscape.Drug association analysis was conducted by Web Gestalt.Results:GO and KEGG pathway enrichment analysis revealed biological processes,cellular components and molecular functions that were related to cancer and estrogen signaling pathways.KEGG pathway enrichment analysis of the genes in transcription factor-differential expression genes regulatory network showed regulation of cancer,estrogen signaling pathways,epidermal growth factor receptor tyrosine kinase inhibitor resistance,and endocrine resistance.Moreover,drug association analysis revealed that hesperidin affected the expression of the same gene as raloxifene.Conclusions:Hesperidin targets estrogen receptor signaling in estrogen receptor-positive breast cancer cells.Results of this study could trace the molecular mechanism of hesperidin in estrogen receptor-positive breast cancer cells and integrative bioinformatics analysis could accelerate drug discovery and development.

Combinational effects of hexane insoluble fraction of Ficus septica Burm.F.and doxorubicin chemotherapy on T47D breast cancer cells

Objective:To evaluate the effects of n-hexane insoluble fraction(HIF)of Ficus septica leaves in combination with doxorubicin on cytotoxicity,cell cycle and apoptosis induction of breast cancer T47D cell lines.Methods:The in vitro drugs-stimulated cytotoxic effects were determined using MTT assay.Analysis of cell cycle distribution was performed using flowcytometer and the data was analyzed using ModFit LT 3.0 program.Apoptosis assay was earned out by double staining method using ethydium bromide-acridin orange.The expression of cleaved-poly(ADP-ribose)polymerase(PARP)on T47D cell lines was identified using immunocytochemistry.Results:The combination exhibited higher inhibitory effect on cell growth than the single treatment of doxorubicin in T47D cells.In addition,combination of doxorubicin and HIF increased the incidence of cells undergoing apoptosis.HIF could improve doxorubicin cytotoxic effect by changing the accumulation of cell cycle phase from G_2/M to G_1 phase.The combination also exhibited upregulation of cleaved-PARP in T47D cells.Conclusions:Based on this results,HIF is potential to be developed as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle arrest.However,the molecular mechanism need to be explored further.

棱果榕乙酸乙酯萃取物和阿霉素化疗对人类乳腺癌细胞T47D的协同效应（英文）

目的:以往研究已证实,棱果榕树叶的乙醇提取物及其乙酸乙酯萃取物(ethyl acetate soluble fraction,EASF)对人类乳腺癌细胞T47D有很强的细胞毒效应。本研究将进一步明确棱果榕树叶乙醇提取物的EASF联合阿霉素对人类乳腺癌T47D细胞系在细胞毒性、细胞周期阻滞以及诱导细胞凋亡方面的协同效应。方法:使用溴化噻唑蓝四氮唑比色法分析T47D细胞毒性效应,流式细胞仪进行细胞周期分析,ModFitLT3.0程序进行数据处理;采用溴化乙锭/吖啶橙双染色法检测细胞凋亡;免疫组织化学法识别T47D细胞系的聚ADP-核苷酸聚合酶(poly ADP-ribose polymerase,PARP)的表达。结果:EASF(0.875～7μg/mL)与阿霉素(2～8nmol/L)联合使用比单纯使用阿霉素能更有效地抑制T47D细胞生长。此外,二者联合使用能够增加细胞凋亡的发生率。研究发现,EASF能通过改变细胞从G2/M期至G1期而增强阿霉素的细胞毒效应。并且,二者的结合比单独使用能刺激T47D细胞中裂解性PARP的表达。结论:EASF可以通过诱导细胞凋亡和细胞周期停滞加强T47D细胞中的阿霉素活性。

Effect of the water extract of Macrosolen cochinchinensis(Lour.) Tiegh.leaves on 7,12-dimethylbenz[a]antracene induced female mice liver carcinogensis

Liver cancer is the third most common cause of death from cancer worldwide.Recently,natural products were used widely as an alternative therapy for liver cancer.Previous study reported Macrosolen cochnichinensis(Lour.) Tiegh.that grows in the host star fruit inhibited breast cancer cells growth in vitro.This study aims to observe the effect of water extract of M.cochinchinensis leaves(MCE) on Balb/c mice hepatocyte after initiation of 7,12-dimethylbenz[a]anthracene(DMBA) as a liver cancer model inducer.The experiment consisted of four mice groups,corn oil solvent control group,the DMBA dose 20 mg/kgBW p.o.ten times twice a week,DMBA+MCE dose 250 mg/kgBW,and DMBA+MCE 750 mg/kgBW.Extract which was dissolved into 0.5%CMC-Na was administered daily by the oral route 1 week before,during and terminated 1 week after the DMBA induction.At the end of the study,rat livers were collected and stained with Haematoxyllene and Eosin(H&E) method. Administration of MCE could not inhibit hepatic carcinogenesis in DMBA-induced female mice.There was no difference in liver tissue histopathology profile between the extract treatment group and DMBA control group.