PPAR-γ anti-inflammatory functions have received significant attention since its agonists have been shown to exert a wide range of protective effects in many experimental models of neurologic diseases. Rice bran is very rich in polyunsaturated fatty acids, which are reported to act as PPAR-γ partial agonists. Herein, the anti-inflammatory effect of rice bran extract (RBE) through PPAR-γ activation was evaluated in LPS-induced neuroinflammatory mouse model in comparison to pioglitazone (PG) using 80 Swiss albino mice. RBE (100 mg/kg) and PG (30 mg/kg) were given orally for 21 days and LPS (0.25 mg/kg) was injected intraperitoneally for the last 7 days. TNF-α and COX-2 brain contents were evaluated by real-time PCR and immunohistochemical analysis. In addition, NFκB binding to its response element was evaluated alongside with the effect of treatments on IκB gene expression. Furthermore, PPAR-γ sumoylation was also studied. Finally, histopathological examination was performed for different brain areas. RBE administration was found to protect against the LPS-induced inflammatory effects by decreasing the inflammatory mediator expression in mice brains. It also decreased PPAR-γ sumoylation without significant effect on IκB expression or NFκB binding to its response element. The majority of the effects were attenuated in presence of PPAR-γ antagonist (GW9662). Level of significance was set to P < 0.05. Such findings highlight the agonistic effect of RBE component(s) on PPAR-γ and support the hypothesis of involvement of PPAR-γ activation in its neuroprotective effect.

Alzheimer’s disease (AD) is a multifactorial incurable neurodegenerative disorder. To date, cholinesterase inhibitors (ChEI) are the mainstay line of treatment to ameliorate the symptoms of AD. Tacrine and donepezil are considered two important cornerstones of anti-dementia drugs. Accordingly, novel series of hexahydrobenzothienocyclopentapyridines, octahydrobenzo-thienoquinolines, hexahydrocyclopenta(thienoquinoline/thienodipyridine), and octahydropyrido-thienoquinolines were efficiently synthesized from readily available reagent, e.g. cyclohexanones, cyclopentanone, and 1-methyl-piperidin-4-one to afford 14 new compounds. All new compounds were screened against their acetylcholinesterase, butyrylcholinesterase, and β-amyloid protein inhibition. In AChE inhibition assay, compound 3,7-dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[4,5]thieno[2,3-b]quinolin-11-amine (2h) showed IC50 value 9.24 ± 0.01 μM × 10−2 excelling tacrine. Compound 1,7-dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[4,5]thieno[2,3-b]quinolin-11-amine (2e) possess excellent IC50 values 0.58 ± 0.02 μM × 10−2 and 0.51 ± 0.001 μM × 10−4 for both butyrylcholinesterase and β-amyloid protein inhibition assays, sequentially. In silico ADME studies were investigated for the promising members (octahydrobenzo-thienoquinolines 2c, 2d, 2e, 2h, 2i, and octahydropyrido-thienoquinolines 4e) and all the results were illustrated. A comparative docking study was conducted between the promising members and both tacrine and donepezil in both acetyl and butyryl choline active sites. The results revealed extra binding patterns and good agreement with the biological results.

T he study was undertaken to evaluate the protective effect of bone marrow mesenchymal stem cells (BM-MSCs) and Moringa oleifera extract (MOE) against gentamicin (GN)induced nephrotoxicity in male albino rats. Thirty two adult male rats were divided into four groups including the control group, the group injected i.p with a single dose of GN (100 mg/ kg b.w), the group treated orally with MOE (400 mg/kg b.w) for 6 days then injected with a single dose of GN and the group was injected with a single dose of BM-MSCs (5x10 5 cells) by tail vein then injected with GN. At the end of experiment blood and kidney tissue samples were collected for estimation of different biochemical parameters. The results recorded a significant increase in BUN, serum KIM-1, cystatin C, creatinine, sodium and renal MDA accompanied with a significant decrease in serum calcium, renal GSH, SOD and CAT in GN alone-treated group as compared to control group. Co administration of MOE or BM-MSCs before GN injection improved all above parameters when compared with GN administered group. It could be concluded that MOE and BM-MSCs have a therapeutic and protective action against AKI induced by GN administration which manifested by lowering kidney markers and MDA contents and elevation in antioxidant profile.

Alzheimer’s disease (AD) is a multifactorial incurable neurodegenerative disorder. To date, cholinesterase inhibitors (ChEI) are the mainstay line of treatment to ameliorate the symptoms of AD. Tacrine and donepezil are considered two important cornerstones as anti-dementia drugs with potent inhibitory effects. Accordingly, novel series of hexahydrobenzo-thienocyclopentapyridines, octahydrobenzo-thienoquinolines, hexahydrocyclopenta-(thienoquinoline/thienodipyridine) and octahydropyrido-thienoquinolines were efficiently synthesized from readily available reagents e.g. cyclohexanones, cyclopentanone, and 1-methylpiperidin-4-one to afford fourteen new compounds. All new compounds were screened against their acetylcholinesterase, butyrylcholinesterase and β-amyloid protein inhibition. In acetylcholinesterase inhibition assay, compound 3,7-Dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[4, 5]thieno[2,3-b]quinolin-11-amine (2h) showed IC50 value 9.24 ± 0.01 µM x10− 2 excelling tacrine itself. Compound 1,7-Dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[4, 5]thieno[2,3-b]quinolin-11-amine (2e) possessed excellent IC50 values 0.58 ± 0.02 µM x10− 2 and 0.51 ± 0.001 µM x10− 4 for both the butyrylcholinesterase and β-amyloid protein inhibition assays, sequentially. In silico ADME studies were investigated for the promising members (octahydrobenzo-thienoquinolines 2c, 2d, 2e, 2h, 2i, and octahydropyrido-thienoquinolines 4e) and all the results were illustrated. A comparative docking study was conducted between the promising members and both tacrine and donepezil in both acetyl and butyryl choline active sites. The results revealed extra binding patterns and good agreement with the biological results.

New thienopyridine tacrine analogues were efficiently synthesized. Series 2 and 4 enclosed fourteen new compounds. They were screened against their acetyl cholinesterase, butyryl cholinesterase and β-amyloid protein inhibition. In acetyl cholinesterase inhibition assay, 2h showed IC50 value 26.4 ± 0.03 ng/mL excelling tacrine itself. 2e possessed excellent IC50 values 1.7 ± 0.07 and 14.7 ± 0.03 ng/mL for both the butyryl cholinesterase and β-amyloid protein inhibition assays, sequentially. The in silico ADME studies were investigated for the promising members (2c, 2d, 2e, 2h, 2i, and 4e) and all the results were illustrated. A comparative docking study was conducted between the promising members and both tacrine and donepezil in both acetyl and butyryl choline active sites. The results revealed extra binding patterns.