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Ginseng (Panax ginseng Meyer) is a popular traditional herbal medicine used worldwide. Patients often take ginseng preparations with other medicines where the ginseng dose could exceed the recommended dose during long-term administration. However, ginseng-drug interactions at high doses of ginseng are poorly understood. This study showed the possibility of herb-drug interactions between the Korean red ginseng (KRG) extract and cytochrome P450 (CYP) substrates in higher administration in mice. The CYP activities were determined in vivo after oral administration of KRG extract doses of 0.5, 1.0, and 2.0 g/kg for 2 or 4 weeks by monitoring the concentration of five CYP substrates/metabolites in the blood. The area under the curve for OH-midazolam/midazolam catalysed by CYP3A was increased significantly by the administration of 2.0 g/kg KRG extract for 2 and 4 weeks. CYP3A-catalysed midazolam 1'-hydroxylation also increased significantly in a dose- and time-dependent manner in the S9 fraction of mouse liver which was not related to induction by transcription. Whereas CYP2D-catalysed dextromethorphan O-deethylation decreased in a dose- and time-dependent manner in vivo. In conclusion, interactions were observed between KRG extract and CYP2D and CYP3A substrates at subchronic-high doses of KRG administration in mice.

Hyperactivated mTOR signaling in the developing brain has been implicated in multiple forms of pathology including tuberous sclerosis complex (TSC). To date, various phenotypic defects such as cortical lamination irregularity, subependymal nodule formation, dysmorphic astrocyte differentiation and dendritic malformation have been described for patients and animal models. However, downstream networks affected in the developing brain by hyperactivated mTOR signaling have yet to be characterized. Here, we present an integrated analysis of transcriptomes and proteomes generated from wild-type and Tsc1/Emx1-Cre forebrains. This led to comprehensive lists of genes and proteins whose expression levels were altered by hyperactivated mTOR signaling. Further incorporation of TSC patient data followed by functional enrichment and network analyses pointed to changes in molecular components and cellular processes associated with neuronal differentiation and morphogenesis as the key downstream events underlying developmental and morphological defects in TSC. Our results provide novel and fundamental molecular bases for understanding hyperactivated mTOR signaling-induced brain defects which can in turn facilitate identification of potential diagnostic markers and therapeutic targets for mTOR signaling-related neurological disorders.