Differential effects of organosulfur compounds from garlic oil on nitric oxide and prostaglandin E₂ in stimulated macrophages

Objective: We investigated the inhibition of nitric oxide (NO) and prostaglandin E₂ (PGE₂) production by the garlic oil derivatives, diallyl sulfide (DAS), diallyl disulfide (DADS), and allyl methyl sulfide (AMS), in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Methods: Cells were treated with LPS (330 ng/mL) and various concentrations of DAS, DADS, and AMS. NO and PGE₂ released into the medium and expressions of inducible NO synthase and cyclooxygenase-2 protein were measured. Results: All three compounds suppressed stimulated NO production, among which AMS exhibited the least inhibition. Western blot analysis showed that DAS and DADS, but not AMS, inhibited the corresponding inducible NO synthase expression. An in vitro study showed that all three compounds possess NO clearance activity, and that DADS and AMS were more effective than DAS. On the contrary, only DAS inhibited activated PGE₂ production and cyclooxygenase-2 protein expression. Conclusions: The garlic derivatives, DAS, DADS, and AMS, differentially regulated the production of NO and PGE₂ in stimulated macrophages. DAS decreased stimulated NO and PGE₂ production by inhibiting inducible NO synthase and cyclooxygenase-2 expressions, and its enzyme inhibiting and NO clearance activity may also partly contribute to the suppression of NO. DADS inhibited activated NO production by decreasing inducible NO synthase expression and by directly clearing NO, whereas AMS suppressed NO mainly through its direct NO clearance activity. Further, neither DADS nor AMS showed any inhibitory effect on stimulated PGE₂ production.