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 In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of one or more hydroxyl groups (— O H) bonded directly to an aromatic hydrocarbon group. The simplest is phenol, . Phenolic compounds are c ...

. 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 In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic ef ...

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 p ...

mutant mice through reduction of oxidative damage and inactivation of

astrocyte Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...

s and the ERK pathway. The different neuroprotective effects reported in

rodent model Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are na ...

s may be mediated via CB₂ receptors. 4-''O''-Methylhonokiol activates CB₂ receptors and also inhibits the oxygenation of the major endocannabinoid

2-AG 2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present ...

via

COX-2 Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene. ...

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