| First Author | Shal B | Year | 2022 |
| Journal | Int Immunopharmacol | Volume | 109 |
| Pages | 108860 | PubMed ID | 35598479 |
| Mgi Jnum | J:348183 | Mgi Id | MGI:7283830 |
| Doi | 10.1016/j.intimp.2022.108860 | Citation | Shal B, et al. (2022) Coagulansin-A improves spatial memory in 5xFAD Tg mice by targeting Nrf-2/NF-kappaB and Bcl-2 pathway. Int Immunopharmacol 109:108860 |
| abstractText | The present study was designed to investigate the underlying molecular signaling of Coagulansin-A (Coag-A) as a therapeutic agent against Alzheimer's disease (AD). Preliminarily, it exhibited a neuroprotective effect against H2O2-induced oxidative stress in HT-22 cells. The in vivo studies were performed by administering Coag-A (0.1, 1, and 10 mg/kg) intraperitoneally to 5xFAD transgenic (Tg) mouse model. Coag-A (10 mg/kg) significantly attenuated the cognitive decline compared to Tg mice group in the shallow water maze (SWM) and Y-maze test paradigms. The anti-aggregation potential of Coag-A was determined by performing Fourier transform-infrared (FT-IR) spectroscopy and differential scanning calorimeter (DSC) analysis in the prefrontal cortex (PFC) and hippocampal (HC) regions of mice brain. The FT-IR spectra demonstrated the inhibition of amyloid beta (Abeta) through a decrease in beta-sheet aggregation, along with the inhibition of changes in the lipids, proteins, and phospholipids. The DSC analysis displayed a low-temperature exotherm associated with the reversible process of aggregation of soluble protein fractions prior to denaturation. Furthermore, Coag-A treatment displayed a regular density of granule cells in H&E stained sections, along with a reduced amyloid load and PAS-positive granules in all the regions of interest in mice brain. The real-time polymerase chain reaction (q-PCR), western blot and immunohistochemical (IHC) analysis demonstrated antioxidant, anti-inflammatory, and anti-apoptotic effect of Coag-A by enhancing the expression of nuclear factor erythroid-2-related factor (Nrf-2) and reducing nuclear factor kappa B (NF-kappaB) and Bax protein expression. In addition, Coag-A significantly increased the antioxidant enzymes and proteins level, along with a reduced pro-inflammatory cytokines production. |
