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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Iranian Journal of Pharmaceutical Research
- نوع مقاله: Journal Article
- کلمات کلیدی: Apoptosis,caspase,Lamiaceae,Salvia chorassanica
- چکیده:
- چکیده انگلیسی: Salvia chorassanica Bunge is one of the Iranian endemic species of Salvia. There is not any reported literature on S. chorassanica. This study was designed to examine the in-vitro anti-proliferative and proapoptotic effects of the methanol extract of S. chorassanica and its fractions on HeLa cell line. Cells were cultured in EX-CELL®, an animal free medium specially designed for HeLa cell line and incubated with different concentrations of plant extracts. Cell viability was quantified by MTS assay. Apoptotic cells were determined using propidium iodide (PI) staining of DNA fragmentation by flow cytometry (sub-G1 peak). Activity of caspase -3, -8 and -9 was measured by the caspase colorimetric kit assay. S. chorassanica inhibited the growth of malignant cells and the CH2Cl2 fraction was determined as the most cytotoxic fraction in comparison with other fractions. The calculated IC50 values for methanol extract, n-hexane, CH2Cl2 and EtOAc fractions were 8.841, 5.45, 2.38, and 58.03 µg/mL, respectively. S. chorassanica induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that the cytotoxic mechanism is characterized by apoptosis induction. The activity of caspase-3 and 8 proteins in treated HeLa cells was significantly higher than that of the control while caspase-9 activity did not change significantly. Based on the result obtained from our study, the apoptosis pathway involved in S. chorassanica-induced cell death may be through the extrinsic pathway and it can be a novel promising candidate in the treatment of cancer.
- انتشار مقاله: 30-09-1390
- نویسندگان: Heydar Parsaee,Javad Asili,Seyed Hadi Mousavi,Hojjat Soofi,Seyed Ahmad Emami,Zahra Tayarani-Najaran
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Isoprenaline,Cilostamide,Inotropic activity,PDE inhibitor,Rat atria
- چکیده:
- چکیده انگلیسی: Objective(s): Recently, we showed that some new synthetic compounds structurally related to cilostamide (4-(1,2-dihydro-2-oxoquinolin-6-hydroxy)- N-cyclohexyl-N-methylbutanamide), a selective phosphodiesterase 3 (PDE3) inhibitor, produce inotropic effect comparable to that of IBMX (3-isobutyl-1-methylxanthine), a non-selective PDE inhibitor, but with differential chronotropic effect. In this investigation, we compared the pharmacological effects of these compounds as potential cardiotonic agents using the spontaneously beating atria model.
Materials and Methods: In each experiment, rats were treated with reserpine. The atrium was isolated and mounted in an organ bath. We assessed chronotropic and inotropic effects using cumulativelogconcentration-response curves of isoprenaline alone or in combination of each test-compound.
Results: Majority of test compounds augment atria contraction force (ACF) significantly but with different potencies on atrium contraction rate. Cilostamide, MCPIP ([4-(4-methyl piperazin-1-yl)-4-oxobutoxy)-4-methylquinolin-2(1H)-one]), methyl carbostyril compounds- (mc1), mc2 and mc5 increased the isoprenaline effect on ACF synergistically. But, mc6 failed to potentiate the effect of isoprenalin; mc3 and mc4 did not increase ACF, which may be because of their higher hydrophilic nature. It was interesting that mc2, alone or in combination with isoprenaline, produced the highest inotropic effect while it did not affect the basal contraction rate and almost blocked the isoprenaline chronotropic effect.
Conclusion: Combination of mc2 with isoprenaline had synergistic effect on inotropic effect, but this combination reduced isoprenaline chronotropic effect; therefore, these effects cannot be related to reducing B-adrenergic receptors activity. These compounds showed different effects; probably all of them were not mediated via PDE3 inhibition and other mechanisms are involving.- انتشار مقاله: 13-03-1396
- نویسندگان: Azar Hosseini,Reza Shafiee-Nick,Hamid Sadeghian,Heydar Parsaee
- مشاهده
- جایگاه : پژوهشی
- مجله: Avicenna Journal of Phytomedicine
- نوع مقاله: Journal Article
- کلمات کلیدی: Nigella sativa,DNA damage,Serum/glucose deprivation,PC12 cells,Thymoquinone
- چکیده:
- چکیده انگلیسی: Objective: The discovery and development of natural products with potent antioxidant properties has been one of the most interesting and promising approaches in the search for treatment of CNS injuries. The most significant consequence of the oxidative stress is thought to be the DNA modifications, which can become permanent via the formation of mutations and other types of genomic instability resulting cellular dysfunction. Serum/glucose deprivation (SGD) has served as an excellent in vitro model for the understanding of the molecular mechanisms of neuronal damage during ischemia and for the development of neuroprotective drugs against ischemia-induced brain injury. Nigella sativa (N. sativa) seeds and thymoquinone (TQ), its most abundant constituent, have been shown to possess anti-inflammatory, antioxidant, chemopreventive and anti-neoplastic effects both in vitro and in vivo. Therefore, in this study we investigated genoprotective effects of N. sativa and TQ on DNA damage of PC12 cells under SGD condition.
Materials and Methods: PC12 cells were cultured in DMEM medium containing 10% (v/v) fetal bovine serum, 100 units/ml penicillin, and 100 µg/ml streptomycin. Initially cells were pretreated with different concentrations of N. sativa extract (NSE), (10, 50, 250 µg/ml) and TQ (1, 5, 10 µg/ml) for 6 h and then deprived of serum/glucose (SGD) for 18 h. The alkaline comet assay was used to evaluate the effect of these compounds on DNA damage following ischemic insult. The amount of DNA in the comet tail (% tail DNA) was measured as an indicator of DNA damage.
Results: A significant increase in the % tail DNA was seen in nuclei of cells following SGD induced DNA damage (p<0.001). In the control groups, no significant difference was found in the % tail DNA between NSE- or TQ-pretreated and vehicle-pretreated PC12 cells (p>0.05). NSE and TQ pretreatment resulted in a significant decrease in DNA damage following ischemic insult (p<0.001). This suppression of DNA damage by NSE and TQ was found to be dose-dependent.
Conclusion: These data indicate that NSE and TQ have a genoprotective property, as revealed by the comet assay, under SGD condition in PC12 cells.- انتشار مقاله: 06-06-1390
- نویسندگان: Beheshteh Babazadeh,Hamid Reza Sadeghnia,Elham Safarpour Kapurchal,Heydar Parsaee,Sima Nasri,Zahra Tayarani-Najaran
- مشاهده