In Vitro Reversible and Time-Dependent CYP450 Inhibition Profiles of Medicinal Herbal Plant Extracts Newbouldia laevis and Cassia abbreviata: Implications for Herb-Drug Interactions

Abstract

This study evaluated the effects of Newbouldia laevis and Cassia abbreviata extracts on CYP450 enzyme activity. Recombinant CYP450 enzyme and fluorogenic substrates were used for evaluating inhibition, allowing the assessment of herb-drug interactions (HDI). Phytochemical fingerprinting was performed using UPLC-MS. The herbal extracts were risk ranked for HDI based on the IC 50 values determined for each CYP enzyme. Newbouldia laevis inhibited CYP1A2, CYP2C9, and CYP2C19 enzyme activities with K i of 2.84 µg/mL, 1.55 µg/mL, and 1.23 µg/mL, respectively. N. laevis exhibited a TDI (4.17) effect on CYP1A2 but not CYP2C9 and CYP2C19 enzyme activities. Cassia abbreviata inhibited CYP1A2, CYP2C9, and CYP2C19 enzyme activities showing a K i of 4.86 µg/mL, 5.98 µg/mL, and 1.58 µg/mL, respectively. TDI potency assessment for Cassia abbreviata showed it as a potential TDI candidate (1.64) for CYP1A2 and CYP2C19 (1.72). UPLC-MS analysis showed that Newbouldia laevis and Cassia abbreviata possess polyphenols that likely give them their therapeutic properties; some of them are likely to be responsible for the observed inhibition. The observations made in this study suggest the potential for these herbal compounds to interact, especially when co-administered with other medications metabolized by these CYP450 enzymes.

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

“…Traditional medicine has been overshadowed by modern medicine as the means of treatment for human diseases [ 14 , 15 , 16 ]. However, the past few decades have seen an increase in the use of medicinal plants for health promotion and treatment of diseases in many countries including developed countries [ 17 , 18 , 19 , 20 , 21 , 22 ]. Indeed, many medicinal plant extracts are now used as prescription drugs in numerous developed countries such as the UK, Germany, China and France [ 23 , 24 ].…”

Enzyme Kinetics and Molecular Docking Studies on Cytochrome 2B6, 2C19, 2E1, and 3A4 Activities by Sauchinone

“…Actually, long-term intakes of herbs tend to cause TDI which can display late inhibition of metabolic enzymes. Cases of TDI such as plumbagin, silybin, and extract of Cassia abbreviata have been reported in HDIs [ 27 , 31 , 32 ]. Particularly high dose administration of herbs (e.g., g unit of administered herbs) can easily inhibit CYPs.…”

Understanding the relevance of herb–drug interaction studies with special focus on interplays: a prerequisite for integrative medicine

“…4). 34,143 On the contrary, their evidence in support of interplay between CYP3A4 and P-gp mainly comes from limited in vitro and preclinical studies, which generally gets extrapolated for humans. 140 These PK interactions may alter the pharmacodynamic responses.…”

“…Here, it must be highlighted that the probability of HDIs can be much higher than drug–drug interactions, since most herbal medicines (even single-herb products) contain mixtures of pharmacologically active constituents compared to conventional/modern medicines. 1,34 These HDIs could be beneficial or harmful, or even fatal; therefore, a thorough understanding of the eventualities of HDIs is essential so that a successful integration of the modern and complementary alternative systems of medicine could be achieved. Here, in the present review, we summarize all the important points related to HDIs, including types, tools/methods for study, and prediction of the HDI, along with a special focus on interplays between drug metabolizing enzymes (DMEs) and transporters.…”