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

摘要

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 IC>50 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 (IC>50 = 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.