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

Anita Sakarwal; Karishma Sen; Heera Ram; Suman Chowdhury; Priya Kashyap; Sunil Dutt Shukla; Anil Panwar

doi:10.2174/0118715303283666240319062925

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

Endocr Metab Immune Disord Drug Targets. 2024 Apr 2. doi: 10.2174/0118715303283666240319062925. Online ahead of print.

Authors

Anita Sakarwal¹, Karishma Sen¹, Heera Ram¹, Suman Chowdhury², Priya Kashyap², Sunil Dutt Shukla³, Anil Panwar⁴

Affiliations

¹ Department of Zoology, Jai Narain Vyas University, Jodhpur, Rajasthan, 342001, India.
² University School of Biotechnology, GGS Indraprastha University, New Delhi, India.
³ Department of Zoology, Meera Girls College, Udaipur, India.
⁴ Department of Bioinformatics and Computational Biology, CCS Haryana Agricultural University, Hisar, 125004, India.

PMID: 38571361
DOI: 10.2174/0118715303283666240319062925

Abstract

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 LCMS/ 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.

Keywords: Acetylcholinesterase (AChE); apigenin triacetate; butyrylcholinesterase (BuChE); hypercholesterolemia; molecular dynamics; neurodegenerations..