Inhibition of lipid peroxidation and superoxide generation by diterpenoids from Rosmarinus officinalis

Four diterpenoids, carnosic acid (1), carnosol (2), rosmanol (3), and epirosmanol (4), were isolated as antioxidative agents from the leaves of Rosmarinus officinalis by bioassay-directed fractionation. These diterpenoids inhibited superoxide anion production in the xanthine/xanthine oxidase system. Mitochondrial and microsomal lipid peroxidation induced by NADH or NADPH oxidation were also completely inhibited by these diterpenes at the concentration of 3-30 microM. Furthermore, carnosic acid protected red cells against oxidative hemolysis. These phenolic diterpenes were shown to be effective to protect biological systems against oxidative stresses.