Biphasic membrane effects of capsaicin, an active component in Capsicum species.

Capsaicin, an active component in Capsicum species, not only stimulates sensory afferent neurons but also inhibits bacterial growth and platelet aggregation. To address the pharmacological mechanism of non-neuronal actions, the effects of capsaicin and its structural analog (N-vanillylnonanamide) on membrane fluidity were studied by measuring fluorescence polarization of liposomes prepared with different phospholipids and cholesterol. Capsaicin and the analog changed membrane fluidity over the concentration range of 50-500 microM differentially with varying concentrations and membrane lipid composition. They showed biphasic effects on 100 mol% 1-palmitoyl-2-oleoylphosphatidylcholine liposomes and 40 mol% cholesterol-containing 1-palmitoyl-2-oleoylphosphatidylcholine liposomes to fluidize and rigidify both liposomal membranes at low and high concentrations, respectively. Changes in membrane fluidity occurred at concentrations corresponding to their reported antibacterial and antiplatelet concentrations. Antibacterial (geraniol and lidocaine) and antiplatelet reference compounds (4-ethylphenol and benzyl alcohol) concentration-dependently fluidized membranes, while not showing biphasic effects. Comparing the potency to fluidize membranes, capsaicin was almost comparable to geraniol and 4-ethylphenol, and more active than lidocaine and benzyl alcohol. The membrane effects of capsaicinoids are responsible for their non-neuronal antibacterial and antiplatelet actions, although they are not the simple membrane fluidizers.