Inhibitory action of Oren-gedoku-to extract on enzymatic lipid peroxidation in rat liver microsomes

We examined the inhibitory action of the extract of Oren-gedoku-to, a tradi tional herbal medicine known to act as an antioxidant, on enzymatic lipid p eroxidation in rat liver microsomes. Simultaneous addition of a spray-dried preparation of Oren-gedoku-to extract (Tsumura TJ-15) inhibited enzymatic lipid peroxidation induced by reduced beta -nicotinamide adenine dinucleoti de phosphate (NADPH) and ADP/Fe3+ complex in liver microsomes in a dose-dep endent manner. When the inhibition by TJ-15 of enzymatic lipid peroxidation in liver microsomes was kinetically analyzed, this medicine showed a compe titive inhibition against NADPH or ADP/Fe3+ complex. TJ-15 inhibited the NA DPH-driven enzymatic reduction of ADP/Fe3+ complex or cytochrome c in liver microsomes competitively. TJ-15 enhanced NADPH consumption by liver micros omes with ADP/Fe3+ complex. Treatment with TJ-15 after the onset of enzymat ic lipid peroxidation in liver microsomes inhibited the progression of lipi d peroxidation in a dose-dependent manner. The present results indicate tha t Oren-gedoku-to extract inhibits enzymatic lipid peroxidation in rat liver microsomes in the initiation and propagation steps in a dose-dependent man ner. These results also suggest that Oren-gedoku-to extract inhibits enzyma tic lipid peroxidation in rat liver microsomes not only through its antioxi dant action but also through reduction of the supply of electrons derived f rom NADPH to ADP/Fe3+ complex in liver microsomes both in a competitive man ner and through stimulation of NADPH oxidation.