Inhibitory Effects of Dietary Schisandra Supplements on CYP2J2 and CYP2C19 Activities in Human Liver Microsomes

The fruits of Schisandra chinensis have been used as a traditional herbal medicine in Korea, China, and Western countries.However, the inhibitory potential of dietary Schisandra supplements (DSS) against cytochrome P450 activity has not been extensively studied.Many commercial DSS products are formulated with additional herbal extracts or excipients beyond Schisandra chinensis, potentially introducing other bioactive compounds.Therefore, we considered the possibility that compounds not originating from Schisandra chinensis could contribute to CYP inhibition.Our previous study demonstrated that DSS from Nature's Way and Swanson strongly inhibits CYP3A-mediated midazolam hydroxylation, primarily due to the high levels of gomisin B and gomisin C. In this study, we used human liver microsomes to evaluate the CYP2C19 and CYP2J2 inhibitory potential of DSS from five providers (Nature's Way, Only Natural, Planetary Herbals, Swanson, and Thompson).DSS from Thompson inhibited CYP2C19 activity with an IC 50 of 35.4 5.8 g/mL, whereas DSS from Swanson and Nature's Way exhibited lower IC 50 values of 10.7 2.3 and 24.7 6.2 g/mL, respectively.Gomisin B, present in high concentrations in Thompson and Swanson, had an IC 50 of 1.38 1.1 g/mL, whereas gomisin N in Nature's Way showed an IC 50 of 2.27 0.4 g/mL.DSS from Thompson inhibited CYP2J2 activity with an IC 50 of 52.3 5.6 g/mL.We also analyzed active components (silymarin, chlorogenic acid, and luteolin) in the DSS from Thompson to determine their role in CYP2J2 inhibition.Among them, silymarin (IC 50 = 22.2 2.0 g/mL) was identified as the main inhibitor.Further studies are required to assess the clinical relevance of inhibiting CYP2J2 and CYP2C19 by DSS from Thompson, Swanson, and Nature's Way.