Objective: Epilepsy is a chronic neurological disease characterised with seizures. The aetiology of the most generalised epilepsies cannot be explicitly determined and the seizures are pronounced to be genetically determined by disturbances of receptors in central nervous system. Besides, neurotransmitter distributions or other metabolic problems are supposed to involve in epileptogenesis. Lack of adequate data about pharmacological agents that have antiepileptogenic effects point to need of research on this field. Thus, in this review, inflammatory aspects of epileptogenesis has been focussed via considering several concepts like role of immune system, blood–brain barrier and antibody involvement in epileptogenesis.Methods: We conducted an evidence-based review of the literatures in order to evaluate the possible participation of inflammatory processes to epileptogenesis and also, promising agents which are effective to these processes. We searched PubMed database up to November 2015 with no date restrictions.Results: In the present review, 163 appropriate articles were included. Obtained data suggests that inflammatory processes participate to epileptogenesis in several ways like affecting fibroblast growth factor-2 and tropomyosin receptor kinase B signalling pathways, detrimental proinflammatory pathways [such as the interleukin-1 beta (IL-1β)–interleukin-1 receptor type 1 (IL-1R1) system], mammalian target of rapamycin pathway, microglial activities, release of glial inflammatory proteins (such as macrophage inflammatory protein, interleukin 6, C–C motif ligand 2 and IL-1β), adhesion molecules that are suggested to function in signalling pathways between neurons and microglia and also linkage between these molecules and proinflammatory cytokines.Conclusion: The literature research indicated that inflammation is a part of epileptogenesis. For this reason, further studies are necessary for assessing agents that will be effective in clinical use for therapeutic treatment of epileptogenesis.

Pomegranate ( Punica granatum L.) is known to possess pharmacological activities, such as antioxidant and anticancer. In this study, we evaluated the antioxidant potency of a methanolic pomegranate fruit peel extract (PPE) and the relation with its antiproliferative and apoptotic effects on MCF-7 human breast cancer cells. Total phenolic content and antioxidant activity of PPE were determined using the Folin–Ciocalteau and the 2,2-diphenyl-l-picrylhydrazyl free radical methods, respectively. Phenolic acids present in the extract were characterized by a reverse-phase high-performance liquid chromatography (HPLC) method. Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. The apoptotic effects were determined by in situ Tdt-mediated dUTP nick end-labeling assay, and Bax/Bcl-2 mRNA expression levels were measured by reverse transcription–polymerase chain reaction. The extraction yield as a percentage of plant material was 37.97% (wt/wt), and total phenolic content was 331.28 mg of gallic acid equivalents/g of extract. According to HPLC analysis, the most abundant phenolic acid detected in the extract was ellagic acid. MCF-7 cell proliferation decreased depending on PPE concentration (25, 50, 100, 200, and 300 μg/mL) and incubation times (24, 48, and 72 hours). After 48 and 72 hours, the apoptotic cell numbers were significantly increased at 100, 200, and 300 μg/mL PPE concentrations. In addition, expression of the pro-apoptotic gene Bax was increased, and that of the anti-apoptotic gene Bcl-2 was decreased after 200 and 300 μg/mL PPE treatment for 48 and 72 hours. Because PPE reduced cell proliferation and induced apoptosis on MCF-7 cancer cells, we believe that PPE has important antioxidant and apoptotic effects.

Turkey is one of the most important centers of diversity for the genus Achillea L. in the world. Keeping in mind the immense medicinal importance of phenols, in this study, three species growing in Turkey, A. coarctata Poir. (AC), A. kotschyi Boiss. subsp. kotschyi (AK) and A. lycaonica Boiss. & Heldr. (AL) were evaluated for their phenolic compositions, total phenolic contents (TPC), antioxidant properties, wound healing potencies on NIH-3T3 fibroblasts and cytotoxic effects on MCF-7 human breast cancer cells. Comprehensive LC-MS/MS analysis revealed that AK was distinctively rich in chlorogenic acid, hyperoside, apigenin, hesperidin, rutin, kaempferol and luteolin (2890.6, 987.3, 797.0, 422.5, 188.1, 159.4 and 121.2 µg analyte/g extract, respectively). The findings exhibited a strong correlation between TPC and both free radical scavenging activity and total antioxidant capacity (TAC). Among studied species, the highest TPC (148.00 mg GAE/g extract) and TAC (2.080 UAE), the strongest radical scavenging (EC₅₀ = 32.63 μg/mL), the most prominent wound healing and most abundant cytotoxic activities were observed with AK. The results suggested that AK is a valuable source of flavonoids and chlorogenic acid with important antioxidant, wound healing and cytotoxic activities. These findings warrant further studies to assess the potential of AK as a bioactive source that could be exploited in pharmaceutical, cosmetics and food industries.

Proteasome inhibition has recently emerged as a clinically effective anticancer therapeutic approach. The first proteasome inhibitor, bortezomib (Velcade, PS-341), and new proteasome inhibitors including ixazomib have become more important in the development of targeted cancer therapies. Under physiological conditions, MLN9708 (ixazomib citrate), the stable citrate ester drug substance, hydrolyzes rapidly to MLN2238 (ixazomib), the biologically active boronic acid. It is a second-generation proteasome inhibitor, similar to the well-known proteasome inhibitor bortezomib, which is currently being investigated in phase 3 trials as a treatment for multiple Myeloma. Despite the proven efficacy of these drugs in hematologic malignancies, clinical activity is limited to solid tumors such as colon adenocarcinoma. This study is the first to investigate and compare the antiproliferative and apoptotic effects of MLN2238 and bortezomib on human colon adenocarcinoma Caco2 cells. The antiproliferative effects of MLN2238 and bortezomib were determined using WST-1; apoptotic effects of this drug were determined by caspase-3 and a mitochondrial membrane potential (JC-1) activity assay. Expression levels associated with proteasome inhibition and apoptosis of NF-κB and c-myc mRNA were evaluated by RT-PCR. At 24 and 48 h, MLN2238 showed significant time- and concentration-dependent antiproliferative and apoptotic effects on Caco2 cells. Depending on increasing mitochondrial depolarization and caspase-3 activation, MLN2238 induced apoptosis at level similar to that of bortezomib. In addition, MLN2238 downregulated NF-κB and c-myc mRNA expression levels. For the first time, MLN2238 was shown to induce antiproliferative and apoptotic effects on human colon adenocarcinoma cells that are comparable with those of bortezomib; these in vitro data in Caco2 cells support the development of MLN2238 for colon cancer.

Parkinson’s disease (PD) is a chronic, progressive, and age-related neurodegenerative disorder characterized by the loss of midbrain dopaminergic neurons caused by the accumulation of free radicals and oxidative stress. Based on the neuroprotective properties of 2-pyrazoline derivatives, in the current work, 1-(phenyl/4-substituted phenyl)-3-(2-furanyl/thienyl)-5-aryl-2-pyrazolines (3a–i, 4a–i) were synthesized via the cyclization of the chalcones (1, 2) with suitable phenylhydrazine hydrochloride derivatives. All these compounds were investigated for their neuroprotective effects using an in vitro 6-hydroxydopamine (6-OHDA)-induced neurotoxicity model of PD in the rat pheochromocytoma (PC-12) Adh cell line. In addition, some different pharmacokinetic parameters of all compounds were in silico predicted by the QikProp module of Schrödinger’s Maestro molecular modeling package. 4-Methylsulfonylphenyl substituted compounds 3h (20%) and 4h (23%) were determined as the most promising neuroprotective agents related to their inductive roles in cell viability when compared with the 6-OHDA-positive control group (43% and 42%, respectively). Moreover, in silico pharmacokinetic results indicated that all compounds were within the acceptable range intended for human use. According to both in vitro and in silico studies, compounds 3h and 4h draw attention as potential orally bioavailable therapeutic drug candidates against neurodegeneration in PD.