Light-dependent inhibition of protein kinase c and superoxide generation of neutrophils by hypericin, an antiretroviral agent

Hypericin, a photosensitizing plant pigment, has antiretroviral activity. When exposed to light, the inhibition of Friend leukemia virus (FLV)-induced splenomegaly by hypericin was increased. The ID₅₀ was decreased to less than 2.5 μg/mouse by exposure to tungsten light (29 × 10^-3 W/cm² for 3 min). This pigment inhibited phorbol 12-myristate 13-acetate (PMA)-activated protein kinase C of rat brain in a light- and concentration-dependent manner. The ID₅₀ of hypericin and the light intensity for inhibition of PKC were 0.1 μM under a constant light of 29 × 10^-3 W/cm² for 3 min and 5 × 10^-3 W/cm² in the presence of 1 μM hypericin for 3 min, respectively. The PMA-induced respiratory burst of neutrophils was inhibited in the light but stimulated in the dark by hypericin. The ID₅₀ for inhibition of the respiratory burst was similar to that for inhibition of PKC. These results suggest that hypericin might inhibited PKC-mediated processes of intact cells, including PMA-induced superoxide generation of neutrophils by some light-dependent mechanism, and that this mechanism might underlie its light-dependent inhibition of FLV infection.