Neolignans from North American Magnolia species with cyclooxygenase 2 inhibitory activity

Based upon reported ethnomedicinal use by Native Americans, extracts and pure isolates from leaves and seeds of Magnolia grandiflora, M. virginiana, M. acuminata and M. macrophylla, all native to the Southeastern United States, were investigated for their anti-inflammatory potential against cyclooxygenase 2 (COX-2).

The extracts and pure compounds from Magnolia species were tested for their production of prostaglandin E(2) (PGE(2)) using a mouse macrophage (RAW 264.7) assay where cells were stimulated by lipopolysaccharide.

Leaf extracts were moderately active (44-58% inhibition at 50 microg/ml) whereas seed extracts showed significant activity of 54-88% inhibition, respectively. In the seed extract of M. grandiflora, honokiol, magnolol and 4'-O-methylhonokiol strongly inhibited COX-2 (IC(50): 1.2-2.0 microg/ml), 3-O-methylmagnolol was moderately active while a new compound was inactive towards COX-2. The neolignans were not cytotoxic to macrophages (RAW 264.7) and kidney fibroblast (VERO) cells in vitro.

The results indicate that the reported ethnomedicinal use of the investigated Magnolia species is in agreement with anti-inflammatory activity of their respective compounds.