Assessment of extracts from red yeast rice for herb-drug interaction by in-vitro and in-vivo assays

Abstract

Red yeast rice (RYR) is made by fermenting the yeast Monascus purpureus over rice. It is a source of natural red food colorants, a food garnish and a traditional medication. Results of the current study demonstrated that polar fractions of the RYR preparations contained herbal-drug interaction activity, which if left unremoved, enhanced P-glycoprotein activity and inhibited the major drug metabolizing cytochromes P450, i,e, CYP 1A2, 2C9 and 3A4. The data from Caco-2 cell absorption and animal model studies further demonstrated that the pharmacokinetic modulation effect by RYR preparations containing the polar fractions ("untreated" preparation) was greater than that from RYR preparations with the polar fractions removed ("treated" preparation). The data indicates a potential for herb-drug interactions to be present in RYR commonly sold as nutritional supplements when the polar fractions are not removed and this should be taken into consideration when RYR is consumed with medications, including verapamil.

Figure 1. HPLC profiles of “untreated” and “treated” RYR extracts were measured at wavelength of 243nm, sample concentration both at 50 mg/ml.

Figure 2. The influences of “untreated” and “treated” RYR extract on P-gp activity, final concentration of samples was 1.25 mg/ml.

Data are expressed as mean ± SD (n = 3). *P<0.05 and **P<0.01 vs the untreated group (UT) control value.

Figure 3. The study of effects of “untreated” and “treated” RYR extract on (A) CYP1A2, (B) CYP2C9 and (C) CYP3A4 activity, final concentration of samples was 1.25 mg/ml.

Data are expressed as mean ± SD (n = 3). *P<0.05 and **P<0.01 vs the untreated group (UT) control value.

Figure 4. Effects of “untreated” and “treated” RYR extract on the permeability coefficients (P_{eff (A–B)}) of verapamil in the CaCO-2 absorption study, final concentration of samples was 0.5 mg/ml.

Data are expressed as mean ± SD (n = 4).

Figure 5. Plasma concentrations of verapamil in the SD rats of “untreated” and “treated” RYR treated group and the control treated group (saline).

Data are expressed as mean ± SD (n = 4–6).