Localization and Aggregation of Honokiol in the Lipid Membrane

Honokiol, a biphenyl lignan extracted from bark extracts belonging to Magnolia plant species, is a pleiotropic compound which exhibits a widespread range of antioxidant, antibacterial, antidiabetic, anti-inflammatory, antiaggregant, analgesic, antitumor, antiviral and neuroprotective activities. Honokiol, being highly hydrophobic, is soluble in common organic solvents but insoluble in water. Therefore, its biological effects could depend on its bioactive mechanism. Although honokiol has many impressive bioactive properties, its effects are unknown at the level of the biological membrane. Understanding honokiol's bioactive mechanism could unlock innovative perspectives for its therapeutic development or for therapeutic development of molecules similar to it. I have studied the behaviour of the honokiol molecule in the presence of a plasma-like membrane and established the detailed relation of honokiol with membrane components using all-atom molecular dynamics. The results obtained in this work sustain that honokiol has a tendency to insert inside the membrane; locates near and below the cholesterol oxygen atom, amid the hydrocarbon membrane palisade; increases slightly hydrocarbon fluidity; does not interact specifically with any membrane lipid; and, significantly, forms aggregates. Significantly, aggregation does not impede honokiol from going inside the membrane. Some of the biological characteristics of honokiol could be accredited to its aptitude to alter membrane biophysical properties, but the establishment of aggregate forms in solution might hamper its clinical use.