Abstract
Two diterpenoids were prepared from hexane anti-inflammatory extracts of the Spanish
herb Sideritis javalambrensis: ent -13-epi -12α-acetoxymanoyl oxide (= “manoyl oxide F1”) and ent -8α-hydroxy-labda-13(16),14-diene (= “labdane F2”). They were evaluated for possible
anti-inflammatory actions in vitro in the concentration range 10-7 M to 10-4 M, and were compared with aspirin, sodium salicylate, and indomethacin. Neither compound
affected superoxide generation or scavenging and they did not inhibit non-enzymatic
lipid peroxidation. Neither compound affected azurophil granular enzyme secretion
from activated human and rat neutrophils. The diterpenoids were not toxic to the leukocytes
or to washed human erythrocytes up to 3 × 10-5 M but at 10-4 M some leakage of LDH or haemolysis was observed. However, both F1 and F2 inhibited
prostaglandin E2 generation in cultured mouse peritoneal macrophages stimulated by zymosan, ionophore
A23187, melittin, and PMA. Labdane F2 was more potent (approximate IC50 = 3 µM in zymosan-activated macrophages). We conclude that these two natural products
interact with the eicosanoid system, but do not interfere with the other tested leukocyte
functions or with reactive oxygen species, and are essentially non-toxic at sub-maximal
doses. This biochemical profile distinguishes these diterpenoids from the anti-inflammatory
poly-phenolics such as flavonoids obtained from the genus Sideritis , and suggests that medicinal decoctions of these plants are likely to owe any anti-inflammatory
activity to more than one bioactive ingredient.
Key words
Sideritis javalambrensis
- Lamiaceae - diterpenoids - natural products - anti-inflammatory drugs - prostaglandins
- macrophages - neutrophils - lipid peroxidation - NSAIDs - superoxide
