Commiphora Myrrha (Nees) Engl. Resin Extracts Induce Phase-I Cytochrome P450 2C8, 2C9, 2C19, and 3A4 Isoenzyme Expressions in Human Hepatocellular Carcinoma (HepG2) Cells

Abstract Background: Commiphora myrrha (Nees) Engl. (C. myrrha) resin is one of the oldest Middle Eastern herbal medicine used for treatment and prevention of numerous diseases. This resin is prepared in different methods and widely consumed among Saudi Arabian patients. Despite its popularity, no studies have been done on potential modulation effects of C. myrrha resin extracts on human cytochrome P450 (CYP) drug-metabolizing enzyme expression.Methods: The C. myrrha extracts were prepared by two different methods of sonication and boiling resembling the most popular traditional preparations of maceration and decoction, respectively. Both extracts were fingerprinted using high-performance liquid chromatography equipped with ultra-violet detector (HPLC-UVD). The viability of HepG2 cells treated with aqueous extracts was determined using Promega CellTiter-Glo® assay in order to select the efficient and non-toxic resin extract concentrations for phase-I metabolic isoenzyme expression analysis. The isoenzyme gene and protein expression levels of CYP 2C8, 2C9, 2C19, and 3A4 were measured using reverse transcription-quantitative polymerase chain reaction and Western blot technologies, respectively. Results: The HPLC-UVD fingerprinting revealed different chromatograms for C. myrrha extracts indicating possible differences in their modulation effects on CYP expression. Both aqueous extracts were toxic to HepG2 cells when tested at concentrations exceeding 150 µg/ml of dry crude extract. The CYP 2C8, 2C9, and 2C19 mRNA expression levels increased up to 4.0-fold after cell treatment with concentrations ranging from 1 to 30 µg/ml C. myrrha extracts, as compared with the untreated cells. However, the modulation of CYP3A4 mRNA expression levels was only significant at 30 µg/ml of crude extract exceeding the 2.0-fold cutoff. The up-regulation of CYP mRNA expression levels induced by C. myrrha extracts was confirmed at the CYP protein expression levels as well. Conclusions: The C. myrrha aqueous extracts modulate CYP 2C8, 2C9, 2C19, and 3A4 gene expression at clinically-relevant concentrations regardless of preparation methods. Further in vitro and in vivo experiments are required for the establishment of herb-drug interaction profile for these traditional medicinal resin extracts.