Peppermint (Mentha piperita L.) extract effectively inhibits cytochrome P450 3A4 (CYP3A4) mRNA induction in rifampicin-treated HepG2 cells.

Interaction between foods and drugs is an important consideration in pharmaceutical therapy. Therefore, here, we examined the suppressive effects of the extracts from seven edible herbs on the induction of CYP3A4 gene expression in rifampicin-treated HepG2 cells. We evaluated the structure and suppressive activity of the most effective active compound isolated from dried peppermint (Mentha piperita L.). The structure of the compound was identified as that of pheophorbide a based on spectroscopic data. It suppressed the induction of CYP3A4 mRNA expression by rifampicin in a dose-dependent manner. Quantitative high-performance liquid chromatography showed that 2 g of dry leaves 0.43 mg in one cup of peppermint tea. These findings demonstrate that pheophorbide a suppresses the induction of CYP3A4 mRNA expression in rifampicin-treated HepG2 cells. Pheophorbide is known to cause photosensitivity. However, the effective dose of pheophorbide a that had a suppressive effect was very low, indicating a high safety margin. Abbreviations: DAD: diode array detector; DMEM: Dulbecco's modified Eagle's medium; ELISA: enzyme-linked immunosorbent assay; HPLC: high-performance liquid chromatography; PCR: polymerase chain reaction; PXR: pregnane X receptor; CAR: constitutive androstane receptor; AHR: aryl hydrocarbon receptor; TLC: thin-layer chromatography.

Effective cytochrome P450 (CYP) inhibitors isolated from tarragon (Artemisia dracunculus).

Two effective cytochrome P450 (CYP) inhibitors were isolated from tarragon, Artemisia dracunculus. Their structures were spectroscopically identified as 2E,4E-undeca-2,4-diene-8,10-diynoic acid isobutylamide (1) and 2E,4E-undeca-2,4-diene-8,10-diynoic acid piperidide (2). Both compounds had dose-dependent inhibitory effects on CYP3A4 activity with IC50 values of 10.0 ± 1.3 µM for compound 1 and 3.3 ± 0.2 µM for compound 2, and exhibited mechanism-based inhibition. This is the first reported isolation of effective CYP inhibitors from tarragon (Artemisia dracunculus) purchased from a Japanese market.

Evaluation of the effect of flavangenol on serum lipid peroxide levels and development of atherosclerosis in spontaneously hyperlipidemic B6.KOR-Apoeshl mice.

Antioxidative flavonoids are used to reduce the risk of cardiovascular diseases in humans. However, the precise mechanism for the anti-atherosclerotic actions of flavonoids remains to be elucidated. In the present study, to assess the mechanism for the action of antioxidative flavonoids on atherosclerosis, we investigated the effect of flavangenol, one of the most potent antioxidants currently known, on spontaneously hyperlipidemic B6.KOR-Apoeshl mice. Flavangenol was orally administered to B6.KOR-Apoeshl mice ad libitum (6 mg flavangenol/mouse/day). After 6 months, serum levels of lipids (total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol) and lipid peroxide were measured, and histopathological changes (lipid accumulation and inflammatory cell infiltration) in the aortic root were evaluated. Serum levels of total cholesterol and LDL-cholesterol were markedly increased, and HDL-cholesterol levels were decreased in B6.KOR-Apoeshl mice compared to C57BL/6 mice used as a control (p<0.001). Among these serum lipids, only HDL-cholesterol levels were significantly increased by flavangenol administration (p<0.05). Moreover, Oil Red O staining (lipid accumulation) was significantly increased in B6.KOR-Apoeshl mice compared to C57BL/6 mice (p<0.001). Notably, flavangenol administration significantly suppressed the increase in Oil Red O staining (p<0.01). Similarly, inflammatory cell infiltration into the intima was significantly increased in B6.KOR-Apoeshl mice compared to C57BL/6 mice (p<0.01), and flavangenol administration significantly suppressed the inflammatory cell infiltration (p<0.01). Importantly, flavangenol administration significantly reduced the increase of serum lipid peroxide levels in B6.KOR-Apoeshl mice (p<0.05). Together, these observations indicate that flavangenol, one of the most potent antioxidants, exerts its anti-atherosclerotic action on spontaneously hyperlipidemic and atherosclerotic B6.KOR-Apoeshl mice, possibly by increasing HDL-cholesterol levels and reducing lipid peroxide levels, thereby suppressing the lipid accumulation (formation of atherosclerotic lesions) and inflammatory cell infiltration (chronic inflammation) in the intima of the aortic root.