Auraptene has neuroprotective and memory enhancing effects in a rat model of Alzheimer’s disease

@#Background: Auraptene is a simple coumarin that exhibits multiple protective activities in the brain. Alzheimer’s disease is a complex, multifactorial, and progressive neurodegenerative disease. Microinjection of the β-amyloid peptide (Aβ) into the hippocampus of rat has been recognized as a reliable and stable animal model of Alzheimer’s disease, which mimics the memory deficits. In the present study, the memory enhancing effects of auraptene were studied in rats that Aβ was injected into their hippocampus to create a model of Alzheimer’s disease. Methods: Different doses of auraptene (5, 10 and 25 mg/kg) were administered intraperitoneally to male Wistar rats. The spatial memory performance was tested by Morris water maze after Alzheimer`s induction. The hippocampal expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were calculated for evaluating the neuroprotective and anti-apoptotic effects of Auraptene in the brain tissue. Results: In comparison with the control group, auraptene significantly decreased the escape latency time in the treated rats. In addition, auraptene increased the percentage of time spent and traveled pathway in the target quadrant. Molecular data showed that auraptene attenuated the Bax/Bcl-2 ratio in the hippocampus of rats. Conclusion: This study demonstrated the memory enhancing effect of Aur after Aβ injection, which could be through inhibiting the apoptotic pathways in the hippocampus of rats.

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

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