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Background: Scrophularia atropatana contains chemicals activating the GABA system and inhibiting glutaminergic system. As well as we know, drugs inhibiting glutamate system have analgesic effects and reduce tolerance to the analgesic effects of morphine. In the present study, effect of methanol extract of aerial parts of S. atropatana on tolerance to the analgesic effects of morphine was evaluated. Methods: The aerial parts of S. atropatana were extracted with methanol by maceration and was further analyzed to determine the content of total phenols, antioxidant activity (DPPH method) and analgesic activity. Several groups of mice received drug regimens for 4 days. Group I: Saline (10 ml/kg, i.p.) + Saline (10 ml/kg, i.p.), group II: Morphine (50mg/kg, i.p.) + Saline (10mg/kg, i.p.) and group III: Morphine (50mg/kg, i.p.) + Extract of S. atropatana (100, 200, 400 mg/kg, i.p.)]. On the fifth day the test dose of morphine (9 mg/kg, i.p.) in different groups were assessed. By using hot plate test, the analgesic activity of different doses of the extract was evaluated. Results: Phytochemical screening indicated the presence of total phenolics content of the extract (152 mg GAE/g) and antioxidant activity (RC50 =143µg/ml) in DPPH method. All doses of the extract had analgesic activity. It was found that treatment with extract (100, 200 mg/kg, i.p.) attenuated the development of tolerance to the antinociceptive effect of morphine. Conclusion: The results of the study demonstrate that S. atropatana strongly reduced tolerance to morphine and has analgesic effects. The suggested analgesic effects may be related to the phenolics content and antioxidant activity of the plant alongside inhibition of glutaminergic system.

Purpose: Breast cancer is the most frequent malignancy diagnosed in women both in developed and developing countries. Natural products especially those from herbal origin have high potential in producing drug components with a source of novel structures. The present study was designed to explore the cytotoxic effects and the cell death mechanism of Scrophularia atropatana extracts. Methods: MTT assay was employed to evaluate the cytotoxic activity of the extracts of S. atropatana on the MCF-7 as well as non-malignant cells. Furthermore, induction of apoptosis was evaluated by TUNEL assay, cell death detection ELISA, DNA fragmentation test, western blotting and Real Time PCR. Results: In vitro exposures of the MCF-7 cells with different concentration of S. atropatana extract significantly inhibited their growth and viability and induced apoptosis in the MCF-7 cells. Cleavage PARP protein, decrease in the mRNA expression levels of bcl-2 and increase expression of Caspase-3 and Caspase-9 mRNA, highlights that the induction of apoptosis was the main mechanism of cell death. Moreover the expression study of Caspase-9 mRNA showed that, the extracts have induced apoptosis via intrinsic mitochondrial pathway. Conclusion: Our results demonstrated that dichloromethane extract of Scrophularia atropatana has an apoptotic effects and it can be developed as anticancer agents.

Scrophularia atropatana (S. atropatana), an Iranian plant belonging to the family of Scrophulariaceae, was assigned for its chemical compositions and biological activities of essential oil (EO) and extracts of the aerial parts of the plant during the flowering stage. Combination of GC-MS and GC-FID was assessed for analyzing the chemical compositions of the EO from the aerial parts of S. atropatana. Furthermore, Brine shrimp lethality test and DPPH assay were performed to evaluate general toxicity and free-radical-scavenging properties, respectively. Furthermore, anti-proliferative and antimicrobial activities were assessed by MTT assay and disc diffusion methods correspondingly. Additionally, all the potent samples (extracts) and its fractions in the MTT assay were further studied for the presence of various compounds by GC-MS apparatus. MeOH extract and 40% sep-pak fraction indicated high amounts of total phenolic (TPC), total flavonoid content (TFC), and antioxidant properties. In the case of general toxicity, among the extracts, dichloromethane (DCM) extract showed noticeable effect. Furthermore, DCM extract was indicated potent ability to eliminate breast tumor cells and minimum efficacy on normal cells. Anti-microbial activity of all samples was ignorable. The potent extracts and fractions which had more anti-proliferative activity were further elucidated by GC-MS and showed high amounts of Alkanes and fatty acids. In the case of EO constituents, non-terpenoids were the major compounds. To sum up, it seems BSLT could be a good preliminary approach for evaluating the cytotoxicity in MCF-7 cell line. Additionally, antioxidant activity, TPC, and TFC contents of all samples were in consistent with each other. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer is the most frequent malignancy diagnosed in women both in developed and developing countries. Natural products especially those from herbal origin have high potential in producing drug components with a source of novel structures. The present study was designed to explore the cytotoxic effects and the cell death mechanism of Scrophularia atropatana extracts. Methods: MTT assay was employed to evaluate the cytotoxic activity of the extracts of S. atropatana on the MCF-7 as well as non-malignant cells. Furthermore, induction of apoptosis was evaluated by TUNEL assay, cell death detection ELISA, DNA fragmentation test, western blotting and Real Time PCR. Results: In vitro exposures of the MCF-7 cells with different concentration of S. atropatana extract significantly inhibited their growth and viability and induced apoptosis in the MCF-7 cells. Cleavage PARP protein, decrease in the mRNA expression levels of bcl-2 and increase expression of Caspase-3 and Caspase-9 mRNA, highlights that the induction of apoptosis was the main mechanism of cell death. Moreover the expression study of Caspase-9 mRNA showed that, the extracts have induced apoptosis via intrinsic mitochondrial pathway. Conclusion: Our results demonstrated that dichloromethane extract of Scrophularia atropatana has an apoptotic effects and it can be developed as anticancer agents. [ABSTRACT FROM AUTHOR]

Background and objectives: Scrophularia atropatana (S. atropatana) is endemic to western and central regions of Iran. It belongs to the genus of Scrophularia (family: Scrophulariaceae). These species have been found to possess antibacterial, antitumor and anti-inflammatory properties. Most of these effects were proven to be attributed to the non-volatile components, which were known as secondary metabolites. Iridoids, phenylpropanoids, phenolic acids and flavonoids have been identified as their main secondary metabolites. This investigation was performed to analyze the composition of the essential oil (EO) of S. atropatana and evaluation of its anti-oxidant and total toxicity properties. Methods: About 150 g powder of the air dried parts of S. atropatana was submitted to hydro-distillation and also was successively extracted (with n-hexane, dichloromethane (DCM) and methanol (MeOH)), by using Clevenger and Soxhlet apparatus, respectively. In addition, Essential Oil (EO) was analyzed by GC-MS and GC-FID. Furthermore, the anti-oxidant activity of the extracts, fractions and EO as well as general toxicity were investigated by DPPH and brine shrimp larva assay, respectively. Results: Totally, sixty eight volatile compounds were identified, which constituted 91.78% of the total oil composition. Among the compounds, major constituents were identified as non-terpenoides (59.59%). Moreover, among the extracts and EO, methanol extract demonstrated high free radical scavenging and general toxic activities with RC50 equal 0.143±0.13 mg/mL and LD50 0.271 mcg/mL respectively. Conclusion: Overall, the main constituents of S. atropatana were hydrocarbons. In comparison to other genesis of Scrophularia, antioxidant activity of the essential oil of S. atropatana was less noticeable.

Background: In many cases of breast cancer, the aberrant methylation of TP53 gene leads to uncontrolled cell proliferation and apoptosis inhibition. Moreover, expression of oncogenes which are under the control of P53 protein could be altered. Survivin as a conspicuous example of this category plays important roles in tumorigenesis, drug resistance and apoptosis inhibition. The present study was done to reveal the effects of Scrophularia atropatana extract on epigenetic situation of TP53 gene promoter and the expression levels of anti-apoptotic gene, survivin and its potential for production of cancer epi-drugs. Methods: Cytotoxic effect of dichloromethane extracts of Scrophularia plant on MCF-7 cell line was assessed in our previous study. Cell death ELISA (enzyme-linked immunosorbent assay) and TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) tests were used to investigate the occurrence of apoptosis in the treated cells. Methylation Specific PCR (MSP) was employed to assess the changes in methylation status of the TP53 gene promoter. Furthermore, quantitative real time PCR was utilized to evaluate the resulting changes in TP53 and survivin genes expression. Results: Cell death ELISA and TUNEL assays confirmed the occurrence of apoptosis. MSP test revealed a significant change in the methylation status of TP53 promoter. QRT-PCR showed an increased TP53 gene expression in the treated cells while a significant decrease in survivin mRNA was evident. Conclusions: According to the outcomes, dichloromethane extract of S. atropatana returned the TP53 gene promoter hypermethylation to normal state. This plant could be a promising source for production of epi-drugs due to its apoptotic effects and reversal of TP53 epigenetic alterations., (Creative Commons Attribution License)