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*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

1 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)24382-24396
頁數15
期刊ACS Omega
6
發行號38
DOIs
出版狀態已發佈 - 2021 九月 28
對外發佈

ASJC Scopus subject areas

  • 化學 (全部)
  • 化學工程 (全部)

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