4-''O''-Methylhonokiol is a

neolignan The lignans are a large group of low molecular weight polyphenols found in plants, particularly seeds, whole grains, and vegetables. The name derives from the Latin word for "wood". Lignans are precursors to phytoestrogens. They may play a role ...

, a type of phenolic compound. It is found in the bark of ''

Magnolia grandiflora ''Magnolia grandiflora'', commonly known as the southern magnolia or bull bay, is a tree of the family Magnoliaceae native to the Southeastern United States, from Virginia to central Florida, and west to East Texas. Reaching in height, it is a ...

'' and in '' M. virginiana'' flowers. 4-''O''-Methylhonokiol is a CB₂ receptor ligand (K_i = 50 nM), showing inverse agonism and partial agonism via different pathways (cAMP and Ca²⁺), which potently inhibits osteoclastogenesis. 4-''O''-Methylhonokiol further attenuates memory impairment in

presenilin 2 Presenilin-2 is a protein that (in humans) is encoded by the ''PSEN2'' gene. Function Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or the amyloid precursor ...

mutant mice through reduction of oxidative damage and inactivation of astrocytes and the ERK pathway. The different neuroprotective effects reported in rodent models may be mediated via CB₂ receptors. 4-''O''-Methylhonokiol activates CB₂ receptors and also inhibits the oxygenation of the major endocannabinoid 2-AG via COX-2 in a substrate-selective manner, thus leading to potential synergistic effects at CB receptors. The same study also provided data that 4-''O''-methylhonokiol can readily pass the blood–brain barrier.

References

{{DEFAULTSORT:Methylhonokiol, 4-O- Lignans Cannabinoids GABAA receptor positive allosteric modulators