New neolignans from the seeds of Myristica fragrans that inhibit nitric oxide production

Five new 8-O-4′ type neolignans, named myrifralignan A-E (1-5), together with five known analogues (6-10), were isolated from the seeds of Myristica fragrans Houtt. Their chemical structures were determined using several spectroscopic methods. Compounds 3-10 exhibited potent inhibitory activity against the production of nitric oxide (NO) in the RAW264.7 cell line stimulated by lipopolysaccaride. Myrislignan (7) and machilin D (10) were the most potent inhibitors of NO production amongst these compounds. The IC50 values of myrislignan and machilin D were 21.2 and 18.5 μM. And, their inhibitory activity was more than L-N6-(1-iminoethyl)-lysine, a selective inhibitor of inducible nitric oxide synthase (IC50 = 27.1 μM). Furthermore, real-time PCR analysis revealed that these neolignans could significantly suppress the expression of inducible nitric oxide synthase mRNA. These results demonstrated that the 8-O-4′ type neolignans are promising candidates as anti-inflammatory agents.