RESUMEN
Background: Huntington's disease is an inherited progressive neurodegenerative disorder caused by an expansion of the polyglutamine tract leading to malformation and aggregation of the mutant huntingtin protein in the cell cytoplasm and nucleus of affected brain regions. The development of neuroprotective agents from plants has received considerable research attention. Objective: Our study aims to investigate the neuroprotective effects of luteolin and the mechanisms that underline its potential mediated protection in the mutant htt neuroblastoma cells. Methods: The mutant htt neuroblastoma cells were transfected with 160Q, and the control wild-type neuroblastoma cells were transfected with 20Q htt for 24 h and later treated with luteolin. Cell viability was determined by MTT and PI staining in both groups, while western blotting was used to evaluate caspase 3 protein expression. Aggregation formation was assessed via immunofluorescence microscopy. Also, western blotting was utilized to measure the protein expression of mutant htt aggregated and soluble protein, Nrf2 and HO-1. The impact of Nrf2 on luteolin-treated neuroblastoma cells was assessed using small interfering RNAs. Results: Our study reports that luteolin can protect cultured cells from mutant huntingtin cytotoxicity, evidenced by increased viability and decreased apoptosis. Also, luteolin reduced the accumulation of soluble and insoluble mutant huntingtin aggregates in mutant htt neuroblastoma cells transfected with 160Q compared to the control wild-type. The mutant htt aggregate reduction mediated by luteolin appeared to be independent of the Nrf2 -HO-1 antioxidant pathway. Conclusion: Luteolin presents a new potential therapeutic and protective agent for the treatment and decreasing the cytotoxicity in neurodegenerative diseases such as Huntington's disease.
RESUMEN
BACKGROUND: We thought to delve deeper into seven meta-analyses of major clinical trials focusing on Glucagon-Like Peptide-One Receptor Agonist (GLP-1 RA) cardioprotective effect. AIM: We explored the role of GLP-1 RA in cardiovascular risk protection as the primary outcome in subjects with type 2 diabetes mellitus. METHODOLOGY: The current review has explored and critically appraised seven meta-analyses of placebo- controlled randomized clinical trials (RCT-s) involving GLP-1 RA used in diabetes that has exhibited major cardiovascular events as the primary outcome. RESULTS: Based on the participants-intervention-comparison and outcomes (PICO), the total number of the participants in this review were (138750), the intervention was conducted with GLP-1 RA, the comparator was a placebo and the outcome was major cardiovascular events. The overall evidence for the cardioprotective effect of GLP-1 RA in diabetes was very clear in subjects with the cardiovascular risk of varying degrees. Most of the currently reviewed meta-analyses have not shown cardioprotection with GLP-1 RA in subjects with diabetes exhibiting high cardiovascular risk or medical history of cardiovascular diseases. Patient variability, in addition to potency parameters, will be the key to a successful member of the class. There will be avenues for selection of a candidate based on the suitability to patient preferences and characteristics. CONCLUSION: The RCT-s for GLP-1 RA should characterize cardiovascular risk in subjects with diabetes such that disparities between established cardiovascular risk (high, moderate and low) or medical history of cardiovascular disease have been accounted for in subgroup analysis.
