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The Synergistic Neuroprotective Effect of Honokiol and Magnolol Against Amyloid-β and MPP+-Induced Neurotoxicity in SH-SY5Y Cells: An Antioxidant, Molecular Orbital, and ADMET Study.

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Title: The Synergistic Neuroprotective Effect of Honokiol and Magnolol Against Amyloid-β and MPP+-Induced Neurotoxicity in SH-SY5Y Cells: An Antioxidant, Molecular Orbital, and ADMET Study.
Authors: Suwansukho B; Department of Pharmacognosy, Faculty of Pharmacy, Srinakharinwirot University, Ongkharak, Nakhon Nayok 26120, Thailand., Poempul K; Department of Pharmacognosy, Faculty of Pharmacy, Srinakharinwirot University, Ongkharak, Nakhon Nayok 26120, Thailand., Samee W; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Srinakharinwirot University, Ongkharak, Nakhon Nayok 26120, Thailand., Tadtong S; Department of Pharmacognosy, Faculty of Pharmacy, Srinakharinwirot University, Ongkharak, Nakhon Nayok 26120, Thailand.
Source: International journal of molecular sciences [Int J Mol Sci] 2026 Jul 08; Vol. 27 (14). Date of Electronic Publication: 2026 Jul 08.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Imprint Name(s): Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms: Lignans*/pharmacology , Lignans*/chemistry , Biphenyl Compounds*/pharmacology , Biphenyl Compounds*/chemistry , Biphenyl Compounds*/pharmacokinetics , Neuroprotective Agents*/pharmacology , Neuroprotective Agents*/chemistry , Amyloid beta-Peptides*/toxicity , Antioxidants*/pharmacology , Antioxidants*/chemistry , 1-Methyl-4-phenylpyridinium*/toxicity, Reactive Oxygen Species/metabolism ; Allyl Compounds ; Phenols ; Humans ; Cell Line, Tumor ; Drug Synergism
Abstract: Alzheimer's disease (AD) and Parkinson's disease (PD) are the two main neurodegenerative diseases and cause disability and death in patients worldwide. Neurodegeneration is characterized by a progressive loss of neuronal function and structure, causing enormous impairment in cognitive-motor function. Magnolol and honokiol are isomeric biphenyl neolignans and have exhibited neuroprotective activity in previous studies. Hence, we assessed and compared honokiol, magnolol, and mixtures of honokiol and magnolol in honokiol/magnolol molar ratios of 1:3, 1:1, and 3:1 in terms of their neurotoxicity, using the cell counting kit-8 (CCK-8) assay, and of their neuroprotective effect on intracellular reactive oxygen species (iROS) against amyloid-beta (Aβ)- and 1-methyl-4-phenylpyridinium ion (MPP+)-induced neurotoxicity in SH-SY5Y cells, using the 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA) assay. The results showed that honokiol (H) and magnolol (M) at 0.1 μM and the mixtures of honokiol and magnolol in H/M ratios of 1:3, 1:1, and 3:1 at 0.0001 μM exhibited a significant neuroprotective effect of reducing iROS in SH-SY5Y cells where neurotoxicity was induced by Aβ- and MPP+ (p-value with respect to Aβ-treated cells < 0.005 and p-value with respect to MPP+-treated cells < 0.0001). Moreover, magnolol and honokiol possess antioxidant properties according to computational molecular analysis with Highest Occupied Molecular Orbital (HOMO)- Lowest Unoccupied Molecular Orbital (LUMO) prediction, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and Ferric Reducing Antioxidant Power (FRAP) assays. The mixtures of honokiol and magnolol exerted synergistic neuroprotective ability at all ratios while showing better antioxidation ability than that of pure magnolol alone but comparable to that of pure honokiol alone. Drug-likeness, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction, and toxicity profiles showed that both compounds are promising neuroprotective agents and that one of the possible targeting mechanisms is the ROS-mediated oxidative stress pathway. Additional neuronal cell lines and in vivo models are required to determine similar effects or other protective mechanisms involving the neuroprotective ability of honokiol and magnolol.
Grant Information: Grant No. 634/2568 Srinakharinwirot University
Contributed Indexing: Keywords: MPP+; amyloid-beta; honokiol; magnolol; neuroprotective effect; synergistic effect
Substance Nomenclature: 11513CCO0N (honokiol)
0 (Lignans)
0 (Allyl Compounds)
0 (Biphenyl Compounds)
0 (Phenols)
001E35HGVF (magnolol)
0 (Neuroprotective Agents)
0 (Amyloid beta-Peptides)
0 (Antioxidants)
0 (Reactive Oxygen Species)
R865A5OY8J (1-Methyl-4-phenylpyridinium)
Entry Date(s): Date Created: 20260728 Date Completed: 20260729 Latest Revision: 20260730
Update Code: 20260730
PubMed Central ID: PMC13410865
DOI: 10.3390/ijms27146096
PMID: 42511444
Database: MEDLINE
Description
ISSN:1422-0067
DOI:10.3390/ijms27146096