TY - JOUR
T1 - Computational and Experimental Assessments of Magnolol as a Neuroprotective Agent and Utilization of UiO-66(Zr) as Its Drug Delivery System
AU - Santos, Joshua
AU - Quimque, Mark Tristan
AU - Liman, Rhenz Alfred
AU - Agbay, Jay Carl
AU - Macabeo, Allan Patrick G.
AU - Corpuz, Mary Jho Anne
AU - Wang, Yun Ming
AU - Lu, Tsai Te
AU - Lin, Chia Her
AU - Villaflores, Oliver B.
N1 - Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society
PY - 2021/9/28
Y1 - 2021/9/28
N2 - 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.
AB - 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.
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U2 - 10.1021/acsomega.1c02555
DO - 10.1021/acsomega.1c02555
M3 - Article
AN - SCOPUS:85116073800
SN - 2470-1343
VL - 6
SP - 24382
EP - 24396
JO - ACS Omega
JF - ACS Omega
IS - 38
ER -