Neuroprotective Efficacy of Phytoconstituents of Methanolic Shoots Extract of Calligonum polygonoides L. in Hypercholesterolemia-associated Neurodegenerations

Background Small molecule phytocompounds can potentially ameliorate degenerative changes in cerebral tissues. Thus, the current study aimed to evaluate the neuroprotective efficacy of phytocompounds of methanolic shoots extract of Calligonum polygonoides L. (MSECP) in hypercholesterolemia-associated neurodegenerations. Methods Phytochemical screening of the extract was made by LCMS/MS and validated by a repository of the chemical library. The hypercholesterolemia was induced through the intraperitoneal administration of poloxamer-407 with a high-fat diet. The in-silico assessments were accomplished by following the molecular docking, ADME and molecular dynamics. MMPBSA and PCA (Principal Component Analysis) analyzed the molecular dynamics simulations. Consequently, in-vivo studies were examined by lipid metabolism, free radical scavenging capabilities and histopathology of brain tissues (cortex and hippocampus). Results 22 leading phytocompounds were exhibited in the test extract, as revealed by LC-MS/MS scrutiny. Molecular docking evaluated significant interactions of apigenin triacetate with target proteins (HMGCR (HMG-CoA reductase), (AChE-Acetylcholinesterase) and (BuChE- Butyrylcholinesterase). Molecular dynamics examined the interactions through assessments of the radius of gyration, RSMD, RSMF and SASA at 100 ns, which were further analyzed by MMPBSA (Molecular Mechanics Poisson-Boltzmann) and PCA (Principal Component Analysis). Accordingly, the treatment of test extract caused significant alterations in lipid profile, dyslipidemia indices, antioxidant levels and histopathology of brain tissues. Conclusion It can be concluded that apigenin triacetate is a potent phytoconstituent of MSEPC and can interact with HMGCR, AChE, and BuChE, which resulted in improved hypercholesterolemia along with neuroprotective ameliorations in the cortex and hippocampus.