Interaction of the Medicinal Plant Piper Rivinoides Ethanolic Extract, Fractions, and Isolated Neolignans with Rat CYP1A Activity

Piper rivinoides Kunth, known in Brazil as “aperta-ruão,” is a medicinal glabrous shrub (3 to 6 m high) that belongs to the Piperaceae family. Some bioactive benzofuran neolignans were isolated from this species, and it is important to know about how these compounds interact with cytochrome P450 enzymes. For this purpose, we tested the ethanolic extract from leaves of P. rivinoides and its partitions in hexane and dichloromethane and in three isolated neolignans (eupamotenoid-5, eupamotenoid-6, and conocarpan) in the activity of the CYP1A isoforms. Little is known about the interaction of neolignans with cytochrome P450 enzymes. Activities of 7-ethoxyresorufin-O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD), markers for CYP1A1 and CYP1A2, respectively, were assayed. The CYP1A (EROD) activity half-maximal inhibitory concentrations (IC50) were determined for plant material and pure compounds. IC50 for quercetin and α-naphthoflavone were also determined for comparative purposes. The hexane partition shows the strongest inhibitory effect (IC50 14.24 ± 0.13 µg/ml) in EROD assay. The three neolignans proved to be potent inhibitors of CYP1A, and eupomatenoid-5 and eupomatenoid-6 inhibited CYP1A2 isoform. A comparison of neolignan three-dimensional structures with the structures of quercetin and α-naphthoflavone indicated that, while eupamotenoid-5 and eupamotenoid-6 overlapped in the same plane, conocarpan overlapped out of plane. This might explain the differences in inhibitory potency. This is the first report on CYP1A inhibition by bioactive benzofuran neolignans.