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.