Novel anti-inflammatory plant labdanes: comparison of in vitro properties with aspirin and indomethacin.

Two purified plant products were obtained from anti-inflammatory extracts of the Spanish herb Sideritis javalambrensis: ent-13-epi-12 alpha-acetoxy-manoyl oxide (= "manoyl oxide F1") and ent-8 alpha-hydroxy-lambda-13(16),14-dien (= "labdane F2"). They were evaluated for possible anti-inflammatory actions in vitro, and were compared with aspirin, sodium salicylate and indomethacin. Neither of the natural products affected superoxide generation or scavenging and they did not affect granular enzyme secretion from activated human and rat neurotrophils. The compounds were not toxic to the cells at up to 10(-4) M. However, both F1 and F2 inhibited thromboxane B2 and leukotriene B4 generation by A23187-treated rat peritoneal leukocytes, suppressing leukotriene generation at 10(-5) to 10(-4) M and thromboxane B2 at 10(-4) M. Labdane F2 also inhibited human secretory synovial phospholipase A2 activity at 10(-3) M, a property not shared by manoyl oxide F1. We conclude that these two natural products interact with the eicosanoid system, perhaps at the phospholipase level, but do not interfere with the other tested leukocyte functions or with reactive oxygen species, and are essentially non-toxic at the doses used.