Glimepiride mitigates tauopathy and neuroinflammation in P301S transgenic mice: role of AKT/GSK3ß signaling.

BACKGROUND AND OBJECTIVE: Tauopathy is a group of neurodegenerative diseases in which the pathogenesis processes are related to tau protein. The imbalances between the activities of kinases and phosphatases of tau protein lead to tau hyperphosphorylation and subsequent neurodegeneration. Numerous studies suggest a strong linkage between type 2 diabetes mellitus (T2D) and neurodegenerative diseases. Therefore, finding a drug with a dual therapeutic activity against T2D and neuroprotective will be a promising idea. Hence, the potential neuroprotective effect of Glimepiride (GPD) against tauopathy was evaluated in the current study. METHODS: P301S mice model was employed for tauopathy and C57BL/6 wild type mice (WT) was used as control. Phosphorylated and acetylated tau protein levels was assessed in cortex and hippocampus by western blot. Effect of GPD on tauopathy related enzymes, neuroinflammation, apoptotic markers were evaluated. Furthermore, the neuroprotective effects against anxiety like behavior and motor impairment was analyzed using Parallel rod floor and Open field tests. RESULTS: GPD significantly ameliorates motor impairment, anxiety like behavior and neurodegeneration in P301S mice. Phosphorylated tau and acetylated tau were significantly decreased in both cortex and hippocampus of P301S mice via decreasing GSK3ß, increasing ratio of phosphorylated-AKT to total-AKT, increasing PP2A and normalization of CDK5 levels. Furthermore, GPD treatment also decreased neuroinflammation and apoptosis by reducing NF-kB, TNF-α and caspase 3 levels. CONCLUSION: The current data suggests that GPD exerts a protective effect against tauopathy, behavioural consequences, neurodegeneration, neuroinflammation and apoptosis. GPD is therefore a promising agent for the treatment of neurodegenerative diseases associated with tauopathy.

Adrenal gland abnormalities detected by magnetic resonance imaging in patients with antiphospholipid syndrome.

BACKGROUND: Adrenal infarction is a rare complication of antiphospholipid syndrome (APS). OBJECTIVES: The purpose of the current study is to detect and study the magnetic resonance imaging (MRI) findings of adrenal glands in APS patients. MATERIALS AND METHODS: In a cross-sectional study, the data of 20 patients with primary or secondary APS were compared to 20 SLE patients without antiphospholipid antibody (aPL) syndrome (controls). MRI of the abdomen showing the adrenal glands was performed. RESULTS: Of the patients, 80% were females with a mean age 32.45 ± 9.93 years, and mean disease duration of 46.65 ± 58.71 months. Adrenal gland abnormalities in the MRI study were detected in 35 % of APS patients vs. no abnormalities detected in the SLE controls. Adrenal gland enlargement was found in all patients (35 %). Capsular enhancement (infarction or hemorrhagic infarction) was found in 5 patients, increased stranding of the surrounding fat planes (inflammatory process) in 4 patients and increased signal on T1WI and T2WI (hemorrhage) in 3 patients. In patients with adrenal gland involvement, 71.4 % had triple aPL positivity compared to 23.1 % in patients with normal adrenal findings (p = 0.04). CONCLUSIONS: Adrenal gland abnormalities on MRI were detected in 35 % of the APS patients (whether primary or secondary); thus, increased focus on management is needed. This percentage is not small and needs to be focused on in terms of management.

A new cytotoxic acylated apigenin glucoside from Phyllanthus emblica L.

A new acylated apigenin glucoside (apigenin-7-O-(6''-butyryl-beta-glucopyranoside) (1) was isolated from the methanolic extract of the leaves of Phyllanthus emblica L. (Euphorbiaceae) together with the known compounds; gallic acid (2), methyl gallate (3), 1,2,3,4,6-penta-O-galloylglucose (4) and luteolin-4'-O-neohesperiodoside (5). Their chemical structures were elucidated on the basis of spectroscopic studies ((1)H NMR, (13)C NMR, DEPT, HSQC, HMBC).

A new pyrrole alkaloid isolated from Arum palaestinum Boiss. and its biological activities.

The phytochemical analysis of the ethyl acetate fraction of Arum palaestinum Boiss. (Araceae) led to the isolation and identification of a new polyhydroxy alkaloid compound; (S)-3,4,5-trihydroxy-1 H-pyrrol-2(5H)-one (1), and other five known compounds; caffeic acid (2), isoorientin (3), luteolin (4) and vicenin 11 (5), as well as the rare compound 3,6,8-trimethoxy, 5,7,3',4'-tetrahydroxy flavone (6). The structural elucidations of all the compounds were based on spectroscopic data (1H- and 13C-NMR, DEPT, HSQC, HMBC and NOE difference techniques) and comparison with literature data. Investigation of the antioxidant activity of the ethyl acetate fraction indicated its strong scavenging capacity for 1,1 -diphenyl-2-picrylhydrazyl (DPPH) radicals (SC50 3.1+/-0.82 microg/mL). Moreover, the treatment of different human cancer cell lines with the ethyl acetate fraction led to dose-dependant suppression in the proliferation of both breast carcinoma cells (MCF-7; IC50 59.09+/-4.1 microg/mL) and lymphoblastic leukemia cells (1301; IC50 53.1+/-2.9 microg/mL); however, it was found to have no effect on the growth of hepatocellular carcinoma cells (Hep G2).