Peganum harmala L. extract reduces oxidative stress and improves symptoms in 6-hydroxydopamine-induced Parkinson's disease in rats

Parkinson's disease is one of the most common neurodegenerative disorders. There are many documents about the effects of oxidative stress in Parkinson's disease etiology. Angiotensin II activates NADPH dependent oxidases and causes superoxides formation. Peganum harmala L. extract, which has angiotensin converting enzyme [ACE] inhibitory effect, is considered to evaluate oxidative stress inhibition and Parkinson's disease improvement. Male rats weighting 200-250 g were divided into 5 groups: Control, Neurotoxin [injection of 6-hydroxydopamine into left hemisphere substantia nigra], Peganum harmala's seedsaqueous extract [10 mg/kg] and captopril [5 mg/kg]. Peganum harmala and captopril were injected intraperitonealy -144, -120, -96, -72, -48, -24, -2, 4 and 24 h relative to 6-hydroxydopamine injection time. Muscle stiffness, apomorphine induced unilateral rotation, amount of brain's protein oxidation and lipid peroxidation, ACE activity and histology of substantia nigra were assayed in all groups. Peganum harmala improved Muscle stiffness and one-direction rotation behavior significantly. It also reduced brain's lipid and protein oxidation levels in neurotoxin-injected rats significantly. In Peganum harmala group compared to control group, brain's ACE activity was significantly inhibited. In histological study, Peganum harmala prevented degeneration of dopaminergic neurons, too. In conclusion, aqueous extract of Peganum harmala could prevent symptoms and reduced oxidative stress markers in rats with Parkinson's disease induced by 6-hydroxydopamine

McL[-1] is ip regulated by prenylated coumarin, umbelliprenin in jurkat cells

Chronic lymphocytic leukaemia [CLL] is the most common B-cell malignancy in the western world and exists as subtypes with very different clinical courses. Myeloid cell leukemia 1 [McL[-1]] is one member of Bcl-2 family proteins that has been shown to be expressed in various tissues and malignant cells, including CLL, where its expression is significantly associated with a failure to achieve complete remission following cytotoxic therapy. Induction of apoptosis by prenylated coumarin, umbelliprenin, in Jurkat cells was previously shown. We examined whether umbelliprenin can down-regulate McL[-1] gene and protein in Jurkat cells. In this regard cells were incubated by umbelliprenin, and then down- regulation of McL[-1] gene was studied by Real Time PCR method. Moreover, down-regulation of McL[-1] protein was studied by western blot analysis. We showed that, expression of McL[-1] mRNA was increased from 1 hour to 3 hours incubation, but this increase has a scale down pattern. Moreover umbelliprenin could inhibit McL[-1] protein. In conclusion umbelliprenin treatment modulates McL[-1] expression at both the transcriptional and posttranslational levels

Umbelliprenin from Ferula szowitsiana activates both intrinsic and extrinsic pathways of apoptosis in jurkat T-CLL cell line

Umbelliprenin is a prenylated compound, which belongs to the class of sesquiterpene coumarins. It is extracted from dried roots of Ferula szwitsiana collected from the mountains of Golestan forest [Golestan Province, north of Iran]. Induction of apoptosis in Jurkat T-CLL cells has been previously shown. In this study, effect of umbelliprenin on proapoptotic caspases [caspase-8 and -9] and antiapoptotic Bcl-2 family protein was studied. Jurkat cells were incubated with umbelliprenin. Cells were then lysed and activation of proteins was studied by Western blot analysis. In this study, we showed that umbelliprenin activates intrinsic and extrinsic pathways of apoptosis by the activation of caspase-8 and -9 respectively. Inhibition of Bcl-2 was also shown. In conclusion, umbelliprenin induced apoptosis in Jurkat cells through caspase-dependent apoptosis pathway

Investigation of angiotensin-converting enzyme inhibitory effects of medicinal plants used in traditional persian medicine for treatment of hypertension: screening study

Angiotensin converting enzyme [ACE] inhibitors are used widely in the treatment of hypertension and heart failure. These inhibitors such as captopril and enalapril are derived from natural products. In the present study 135 plants used in Traditional Persian Medicine have been investigated for their angiotensin converting enzyme [ACE] inhibitory activity. They were selected on the basis of their usage as antihypertensive, cardiotonics and diuretics. Dried powdered plant material was extracted with mix solution of water and ethanol in ultrasonic bath. The extracts were filtered and concentrated in vacuum except for the water extracts, which were freeze-dried. Test solutions were made by dissolving extract in assay buffer, corresponding to a final concentration of 0.33 mg of crude plant extract in 1 ml test volume. Enzyme assay was performed by HPLC method. Plants exhibiting inhibition levels with more than 50% were further tested for the presence of tannins in order to eliminate possible false positives. In total, 52 Species out of the 135 [39%] screened, gave more than 50% ACE inhibition. Forty Species were found to possess a high ACE inhibiting ability and were low in their tannin content. Traditional medicine based on certain plants could be of beneficial effects in hypertension treatment

Umbelliprenin induces apoptosis in CLL cell lines

Chronic lymphocytic leukemia [CLL] remains an incurable disease that requires innovative new approaches to improve therapeutic outcome. Many Ferula species, including F. asa-foetida, synthesize terpenyloxy coumarins. One of these coumarins is umbelliprenin, which has been implicated with induction of apoptosis in some cancer cell lines. In this study induction of apoptosis by umbelliprenin on Jurkat T-CLL and Raji B-CLL cell lines was studied. In this regard, cells were incubated with various concentrations of umbelliprenin in-vitro for different times and assayed for apoptosis with annexin V-FITC/PI double staining flowcytometry method. Results showed that umbelliprenin induced apoptosis in leukemic cells in a dose- and time-dependent manner and that CLL cells were more susceptible to umbelliprenin induced cell death than normal peripheral blood mononuclear cell [PBMCs]. Moreover, we study the induction of apoptosis in Jurkat cells by umbelliprenin in the presence of interleukin 4 [IL-4] as an agent that causes resistance to apoptosis in CLL cells, was also student. We showed that IL-4 can not reduce apoptotic effect of umbelliprenin. The preferential toxicity of umbelliprenin for CLL cells, supports the hypothesis that oral administration of umbelliprenin in the form of foods or folk medicines containing this coumarin, might enhance protection against the development of CLL in man with little side effects. In conclusion, umbelliprenin may be an effective therapeutic agent in the treatment of CLL, and thus clinical studies with umbelliprenin may be appropriate

Acute phase reactants as a prognostic factor in acute stroke

Elevated levels of CRP are present among patients at risk for further first-ever myocardial infarction and stroke. It has been shown that after ischemic stroke, increased levels of CRP are associated with unfavorable outcomes. From 120 patients admitted to the emergency unit of our hospital with the diagnosis of stroke; CRP, D-dimer and ferritin level was measured and the patients were followed until discharge or death. CRP level was significantly different between the patients with TIA and stroke. D-Dimer level was also significantly different between the TIA and the admitted groups. Ferritin was not different between the prognosis groups. There was a correlation between CRP and D-Dimer [r = 0.381, p = 0.001], and also between CRP and ferritin [r = 0.478, p= 0.000]. CRP is a useful adjuvant marker to determine the prognosis of patients with cerebro-vascular events admitted to the hospital, in both patients with stroke positive history and first-ever stroke