Leukotrienes (LTs) are
lipid mediators derived from
arachidonic acid (AA) involved in a number of autoimmune/inflammatory disorders including
asthma,
allergic rhinitis and
cardiovascular diseases.
Salvinorin A (SA), a
diterpene isolated from the hallucinogenic plant Salvia divinorum, is a well-established
analgesic compound, but its anti-inflammatory properties are under-researched and its effects on LT production is unknown to date. Here, we studied the possible effect of SA on LT production and verified its actions on experimental models of
inflammation in which LTs play a prominent role. Peritoneal macrophages (PM) stimulated by
calcium ionophore A23187 were chosen as in vitro system to evaluate the effect of SA on LT production.
Zymosan-induced
peritonitis in mice and
carrageenan-induced
pleurisy in rats were selected as LT-related models to evaluate the effect of SA on
inflammation as well as on LT biosynthesis. SA inhibited, in a concentration-dependent manner, A23187-induced
LTB4 biosynthesis in isolated PM. In
zymosan-induced
peritonitis, SA inhibited cell infiltration,
myeloperoxidase activity, vascular permeability and
LTC4 production in the peritoneal cavity without decreasing the production of
prostaglandin E2. In
carrageenan-induced
pleurisy in rats, a more sophisticated model of acute
inflammation related to LTs, SA significantly inhibited
LTB4 production in the inflammatory exudates, along with reducing the phlogistic process in the lung. In conclusion, SA inhibited LT production and it was effective in experimental models of
inflammation in which LTs play a pivotal role. SA might be considered as a lead compound for the development of drugs useful in LTs-related diseases.