Computational and Experimental Assessments of Magnolol as a Neuroprotective Agent and Utilization of UiO-66(Zr) as Its Drug Delivery System

Joshua Santos, Mark Tristan Quimque, Rhenz Alfred Liman, Jay Carl Agbay, Allan Patrick G. Macabeo, Mary Jho Anne Corpuz, Yun Ming Wang, Tsai Te Lu, Chia Her Lin, Oliver B. Villaflores*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The phenolic natural product magnolol exhibits neuroprotective properties through β-amyloid toxicity in PC-12 cells and ameliorative effects against cognitive deficits in a TgCRND8 transgenic mice model. Its bioavailability and blood-brain barrier crossing ability have been significantly improved using the metal-organic framework (MOF) UiO-66(Zr) as a drug delivery system (DDS). To investigate the neuroprotective effects of the Zr-based DDS, magnolol and magnolol-loaded-UiO-66(Zr) (Mag@UiO-66(Zr)) were evaluated for inhibitory activity against β-secretase and AlCl3-induced neurotoxicity. Due to the moderate inhibition observed for magnololin vitro,in silicobinding studies were explored against β-secretase along with 11 enzymes known to affect Alzheimer’s disease (AD). Favorable binding energies against CDK2, CKD5, MARK, and phosphodiesterase 3B (PDE3B) and dynamically stable complexes were noted through molecular docking and molecular dynamic simulation experiments, respectively. The magnolol-loaded DDS UiO-66(Zr) also showed enhanced neuroprotective activity against two pathological indices, namely, neutrophil infiltration and apoptotic neurons, in addition to damage reversal compared to magnolol. Thus, MOFs are promising drug delivery platforms for poorly bioavailable drugs.

Original languageEnglish
Pages (from-to)24382-24396
Number of pages15
JournalACS Omega
Volume6
Issue number38
DOIs
Publication statusPublished - 2021 Sep 28
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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