The possible mechanism of Datura stramonium on pentobarbital-induced sleep in mice.

BACKGROUND: Insomnia leads to the development of mental problems and missing of accuracy in affected persons. Various investigations have previously revealed which medicinal plants play a role in the improvement of insomnia. In this study, we evaluated the effect of hydro-alcoholic extract of Datura stramonium on insomnia in mice. METHODS: The extracts and fractions at different concentrations were injected intraperitoneally (i.p.) to mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Additionally, the blood was collected from cardiac and serum separated to measure brain-derived neurotrophic factor (BDNF). The LC-MS was done to identify the active components. Flumazenil or naloxone were also applied to study the possible mechanism of extract. The PC12 cells were then exposed to different doses of extract and fractions, in order to evaluate cytotoxicity by MTT assay and the measured LD50. RESULTS: The hydro-alcoholic extracts of calyx, seed and petal elevated sleep duration and decreased sleep latency. In addition, water, ethyl acetate and n-butanol fractions of hydro-alcoholic extract of petal increased sleep duration. Of note, Naloxone significantly reversed the hypnotic effect of the extract. The extract increased the level of BDNF in serums. As well, the toxicity assessment revealed that the extracts had not toxic on PC12 cells. The LD50 value was obtained as 4.8 g/kg. CONCLUSION: This research demonstrated that D. stramonium (including seed, petal and calyx) increased the hypnotic effect without neurotoxicity on PC12 cells. Sleep induction may be related to its active ingredients as well as the effect on opioid receptors.

Attenuation of isoprenaline-induced myocardial infarction by Rheum turkestanicum.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.

Neuroprotective effects of Pinus eldarica in a mouse model of pentylenetetrazole-induced seizures.

OBJECTIVE: Oxidative stress has pernicious effects on the brain. Pinus eldarica has antioxidant properties. We explored neuroprotective effect of P. eldarica against pentylenetetrazole (PTZ)-induced seizures. MATERIALS AND METHODS: Male mice (BALB/c) were grouped as control, PTZ, Soxhlet (Sox) 100, Sox 200, Macerated (Mac) 100 and Mac 200 groups. Sox and Mac extracts (100 and 200 mg/kg) were injected during 7 days. Delay in onset of minimal clonic seizure (MCS) and generalized tonic- clonic seizure (GTCS) was measured. Number of dark neurons (DN) and levels of oxidative stress indicators in the hippocampus were evaluated. RESULTS: Onset of MCS and GTCS was later in groups treated with the extracts than the PTZ group (p<0.01 and p<0.001). Number of DN in the hippocampus in the PTZ group was higher than the control group (p<0.001) while in the extract groups, was lower than the PTZ group (p<0.05, p<0.01 and p<0.001). MDA level was higher whereas total thiol level and activity of SOD and CAT were lower (p<0.001) in the PTZ group than the control group. MDA level in the Sox 100 (p<0.01), Sox 200 (p<0.001) and Mac 200 (p<0.01) groups was less than the PTZ group. Total thiol level in the Sox 200 (p<0.001), SOD in the Sox 100 (p<0.05), Sox 200, and Mac 200 and CAT in the Sox 200 (p<0.001) groups were higher than the PTZ group. CONCLUSION: P. eldarica prevented neuronal death and reduced seizures caused by PTZ via improving brain oxidative stress.

Induction of cytotoxicity and apoptosis in FLT3 mutant expressing cells using novel pyrimido cyanoacrylates and quinoline derivatives.

BACKGROUND: Aberrant activation of FMS-like tyrosine kinase 3 (FLT3) is associated with acute myeloid leukemia (AML). Leukemic cells expressing constitutively active FLT3 mutants are resistance to the current cancer therapies (radiotherapy and chemotherapy); hence, there is an increased interest to identify new agents for the treatment of AML. The main aim of this study was evaluating cytotoxic effects of novel pyrimidocyanoacrylates and quinoline derivatives on FLT3 overexpressing cells. MATERIALS AND METHODS: Five novel pyrimidocyanoacrylates & 2-chloro 3-carbaldehyde quinolone derivative compounds, E1QAC1, E1QAC2, E1QAC3, E1QAC4, and E1QAC5 were designed and synthesized at the Department of Chemistry, Faculty of Sciences, Ferdowsi University, Mashhad, Iran. FDC-P1 cells expressing human wild-type FLT3 (FD-FLT3-WT) and internal tandem duplication (ITD) mutants (FD-FLT3-ITD) used in this study. The cells maintained in DMEM medium supplemented with 10% fetal calf serum (FCS) and murine granulocyte-macrophage colony stimulating factor (mGM-CSF). Potency for induction of cytotoxicity (IC50 value) and apoptosis was determined after treating the cells with concentration of the compounds by resazurin assay. Bax and Bcl2 activation status was also investigated by Western blot analysis. RESULTS: All the compounds had concentration-dependent effects on inhibition of cell proliferation and induction of apoptosis in both cell lines. E1QAC4 was the most potent compound for inhibition of cell proliferation (with IC50 value of 19 µM) and apoptosis induction in the FLT3-WT cells. However, FD-FLT3-ITD cells were nearly five-times more resistant to all the compounds (except than E1QAC2) that the FLT3-WT expressing cells. Western blotting results also showed that FD-FLT3-ITD cells had lower levels of Bax and higher levels of Bcl2 than the FD-FLT3-WT cells. CONCLUSION: The five novel heterocyclic compounds (E1QAC1-5) had cytotoxic effects and induced apoptosis in FD-FLT3 cells. Therefore, it is worthwhile to consider them as potential lead compound for development of new therapeutic agents for AML patients.

Hypnotic Effect of Red Cabbage (Brassica oleracea) on Pentobarbital-Induced Sleep in Mice.

OBJECTIVE: The present study was performed to investigate the effect of hydroalcoholic extract of red cabbage and its fractions on sleeping behavior in mice. MATERIALS AND METHODS: The extract and its fractions were injected to mice and sleep duration as well as sleep latency were recorded. Furthermore, toxicity of the extract was determined both in vivo and in vitro. RESULTS: The extract increased sleep duration at doses of 50-200mg/kg (P < 0.001). This observed hypnotic effect was comparable to that of diazepam (3mg/kg) (P < 0.001 in comparison with control group). Ethyl acetate, n-butanol, and aqueous fractions could increase sleep duration (P < 0.001). The sleep latency was decreased by the extract (P < 0.001) and only ethyl acetate fraction (P < 0.001). LD50 value for red cabbage extract was 2.4g/kg. There was no toxic effect on viability of cultured neuronal cells (PC12). Rotarod test results showed that there were no significant differences between the extract groups and the control group. CONCLUSION: The results suggest that red cabbage potentiates pentobarbital hypnosis without any toxic effect. The main component(s) responsible for this effect is most likely to be intermediate polar agent(s) such as flavonoids, which are found in ethyl acetate fraction of this plant.