GLP-1 mediates the neuroprotective action of crocin against cigarette smoking-induced cognitive disorders via suppressing HMGB1-RAGE/TLR4-NF-κB pathway.

Cigarette smoking (CS) has been associated with an increased risk of cognitive disorders. Although HMGB1 has been connected to various neurological ailments, its role in the pathogenesis of CS-induced cognitive impairments is undefined. With the ability of GLP-1 to lower HMGB1 expression and improve learning and memory performance, we sought to assess the potential neuroprotective efficacy of Crocin (Cro) as a GLP-1 stimulator against CS-induced cognitive impairments, with a focus on the HMGB1-RAGE/TLR4-NF-κB pathway. Fifty adult rats were specified into: Control; Cro (30 mg/kg); CS; Cro then CS and CS concurrently with Cro. Cognitive functions were assessed by MWM, EMP, and passive avoidance tests. Hippocampal levels of GLP-1, HMGB1, pro-inflammatory cytokines, and apoptotic markers were detected using ELISA, western blotting, and immunohistochemistry. Hippocampal oxidant/antioxidant status was evaluated via colorimetric determination of MDA and TAC. The results revealed that Cro either before or along with CS produced a significant improvement in learning and memory. Cro markedly hindered HMGB1-RAGE/TLR4-NF-κB pathway through enhancing GLP-1 level and expression, which in turn suppressed TNF-α and IL-1ß levels and alleviated CS-induced neuroinflammation. Cro significantly counteracted CS-triggered oxidative stress as evidenced by reducing MDA level and raising TAC. Histopathologically, Cro lessened neuronal apoptosis by lowering Bax/Bcl-2 ratio at hippocampal CA2 region. These findings confirmed a GLP-1-dependent neuroprotective action of Cro against CS-induced cognitive disorders via suppressing HMGB1-RAGE/TLR4-NF-κB axis.

Targeting Neprilysin (NEP) pathways: A potential new hope to defeat COVID-19 ghost.

COVID-19 is an ongoing viral pandemic disease that is caused by SARS-CoV2, inducing severe pneumonia in humans. However, several classes of repurposed drugs have been recommended, no specific vaccines or effective therapeutic interventions for COVID-19 are developed till now. Viral dependence on ACE-2, as entry receptors, drove the researchers into RAS impact on COVID-19 pathogenesis. Several evidences have pointed at Neprilysin (NEP) as one of pulmonary RAS components. Considering the protective effect of NEP against pulmonary inflammatory reactions and fibrosis, it is suggested to direct the future efforts towards its potential role in COVID-19 pathophysiology. Thus, the review aimed to shed light on the potential beneficial effects of NEP pathways as a novel target for COVID-19 therapy by summarizing its possible molecular mechanisms. Additional experimental and clinical studies explaining more the relationships between NEP and COVID-19 will greatly benefit in designing the future treatment approaches.