Polyacetylenes from Angelica gigas and their inhibitory activity on nitricoxide synthesis in activated macrophages

In activated macrophages the inducible form of nitric oxide synthase (i-NOS ) generates high amounts of the toxic mediator, nitric oxide (NO) which con tributes to the circulatory failure associated with septic shock. Two polya cetylenes were isolated from the medicinal plant Angelica gigas and their s tructures were elucidated as octadeca-1,9-dien-4,6-diyn-3,8,18-triol (1) an d 18-acetoxy-octadeca-1,9-dien-4,6-diyn-3,8-diol (2) by spectroscopic metho d, These polyacetylenes and their peracetate, 3, 8, 18-triacetoxy-octadeca- 1,9-dien-4,6-diyn (3) inhibited the production of NO in LPS-activated RAW 2 64.7 cells by suppressing the i-NOS enzyme expression. These new inhibitors of i-NOS expression may have potential in the treatment of endotoxemia and inflammation accompanied by the overproduction of NO.