Anticancer effects of various Iranian native medicinal plants on human tumor cell lines

In this study the antineoplastic activity of methanolic extracts of six medicinal plants that are native to Iran, including Galium mite, Ferulago angulata, Stachys obtusicrena, Cirsium bracteosum and Echinophora cinerea was investigated. Different tumor cell lines were exposed to the extracts and cytotoxic analysis using MTT colorimetric assay was performed. Quantification of percentage of cells undergoing apoptotic changes by flow cytometry, and DNA fragmentation analysis on sensitive cell lines was then carried out. Results obtained indicated that almost all of the extracts more or less had the capacity to decrease the proliferation of tumor cells. Among the plants, the highest activity against K562 leukemia cell line was found for E. cinerea and C. bracteosum with IC50 less than 20 microg/ml followed by G. mite with IC50 of 39.8 microg/ml. F. angulata and E. cinerea, mostly inhibited Jurkat cells proliferation (IC50 less than 8 microg/ml). Fifty percent inhibition of Fen bladder cell carcinoma due to exposure to F. angulata and E. cinerea was found at concentrations of nearly 180 microg/ml. A549, a lung carcinoma cell, was mostly affected by S. obtusicrena (IC50 more than 200 microg/ml). In flow cytometry analysis, C. bracteosum, E. cinerea, F. angulata and S. obtusicrena extracts demonstrated no remarkable effects on the cell cycle profile of K562 and Jurkat cells. Moreover, in DNA fragmentation analysis of treated cells, no ladder formation was detected. In contrary, G. mite caused more than 40% apoptosis in the K562 and Jurkat cells. In DNA fragmentation analysis G. mite extract produced ladder formation in these cells. In conclusion, these results indicated that the extracts used in this study have anti tumor activity particularly against the leukemia cell lines and that apoptosis is the possible cause of cell death observed due to the extract of G. mite.     

Galmic, a nonpeptide galanin receptor agonist, affects behaviors in seizure, pain, and forced-swim tests

The pharmacological exploitation of the galanin receptors as drug targets for treatment of epilepsy, depression, and pain has been hampered by the lack of workable compounds for medicinal chemists from random screening of large chemical libraries. The present work uses the tripeptidomimetic galnon and displays its presumed pharmacophores on a rigid molecular scaffold. The scaffold is related to marine natural products and presents three functional groups near one another in space, in a manner reminiscent of a protein surface. An active compound, Galmic, was identified from a small synthetic library and tested in vitro and in vivo for its affinity and efficacy at galanin receptors. Galmic has micromolar affinity for GalR1 receptors (Ki = 34.2 microM) and virtually no affinity for GalR2 receptors. In vitro, Galmic, like galanin, suppresses long-term potentiation in the dentate gyrus; it blocks status epilepticus when injected intrahippocampally or administered i.p. Galmic applied i.p. shows antidepressant-like effects in the forced-swim test, and it is a potent inhibitor of flinching behavior in the inflammatory pain model induced by formalin injection. These data further implicate brain and spinal cord galanin receptors as drug targets and provide an example of a systemically active compound based on a scaffold that mimics protein surfaces.     

Comparing Hippocampal Atrophy in Alzheimer's Dementia and Dementia with Lewy Bodies

Background/Aims: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the two most common neurodegenerative dementias. During the early stages, clinical distinction between them is often challenging. Our objective is to compare hippocampal atrophy patterns in mild AD and mild DLB. We hypothesized that DLB subjects have milder hippocampal atrophy relative to AD subjects. Methods: We analyzed the T1-weighted magnetic resonance imaging data from 113 subjects: 55 AD, 16 DLB and 42 cognitively normal elderly (normal controls, NC). Using the hippocampal radial distance technique and multiple linear regression, we analyzed the effect of clinical diagnosis on hippocampal radial distance, while adjusting for gender and age. Three-dimensional statistical maps were adjusted for multiple comparisons using permutation-based statistics with a threshold of p < 0.01. Results: Compared to NC, AD exhibited significantly greater atrophy in the cornu ammonis (CA)1, CA2-3 and subicular regions bilaterally while DLB showed left-predominant atrophy in the CA1 region and subiculum. Compared directly, AD and DLB did not reveal statistically significant differences. Conclusion: Hippocampal atrophy, while present in mildly impaired DLB subjects, is less severe than atrophy seen in mildly impaired AD subjects, when compared to NC. Both groups show predominant atrophy of the CA1 subfield and subiculum.     

Cerebral Visual Impairment Characterized by Abnormal Visual Orienting Behavior With Preserved Visual Cortical Activation

PurposeChildren with cerebral visual impairment (CVI) often have abnormal visual orienting behaviors due to impaired or damaged visual cortex. Alternatively, visual-cortical function is intact but visual information is not transformed downstream into an appropriate oculomotor output (visuomotor dysfunction). We examined visual, anatomic, and oculomotor assessments to distinguish visuomotor dysfunction from CVI associated with severely reduced visual-cortical response.MethodsWe reviewed the medical records from children with CVI having abnormal visual orienting behaviors, normal ocular examinations, and born near term. Relevant data were visual evoked potentials (VEPs), Teller card acuity, eye movements recorded by video-oculography (VOG), and neuroimaging (magnetic resonance imaging [MRI]) including diffusion tensor imaging (DTI) tractography.ResultsThirty subjects had visuomotor dysfunction based on a normal VEP; of these 33% had a normal MRI and 67% had white matter abnormalities associated with metabolic disease and/or decreased volume of brain parenchyma. VOG recordings showed smooth pursuit gains were uniformly reduced and saccades were dysmetric but followed the main sequence. Ten subjects had severe CVI based on VEPs at noise levels; visual acuities and MRI findings overlapped those of the visuomotor dysfunction group. Developmental delay, seizures, microcephaly, and hypotonia were common across all groups. All subjects with an abnormal conventional MRI had abnormal metrics on DTI tractography from the occipital lobe.ConclusionsA subset of patients with CVI have abnormal visual orienting behaviors despite a normal VEP (visuomotor dysfunction). A majority have abnormal white matter metrics on tractography suggesting a downstream defect in sensorimotor transformation. Clinically, visuomotor dysfunction is indistinguishable from severe CVI.