Cannabinoid and opioid receptor displacement activity of Magnolia grandiflora seeds

Magnolia grandiflora L. (Magnoliaceae), is a plant of medicinal significance. Its flowers and seeds are used in various traditional herbal remedies. Recently, it was reported that M. officinalis and its main constituents, magnolol and honokiol, can activate cannabinoid receptors. The n-hexane extract of the seeds showed significant displacement of cannabinoids CB1, CB2, and opioid δ-, κ-, and µ-receptors. The extract was subjected to CPTLC to afford 4-O-methylhonokiol (1), magnolol (2), and honokiol (3). The CB and opioid receptor displacement assays revealed that compounds 1 – 3 are more selective in displacing radioligand from CB1 and CB2 at 10µM (91.3% and 82.2% for 1), while a mixture of 2+3 showed strong displacement of CB1 and CB2, and µ- and δ-opioid receptors, compared to pure 2 and 3. Compounds 1 – 3 displayed significant displacement affinity and selectivity towards CB2 than CB1, with CB2 Ki values for 1, 2, 3, and 2+3 (1:1 mixture) found to be 0.29, 1.44, 1.94, and 1.78 µM, respectively; CB1 Ki's averaged ˜10-fold higher. In contrast, the mixture was found to have poor displacement for κ-opioid receptors during IC₅₀ and Ki determination.