The inhibitory activity of the extracts of popular medicinal herbs on CYP1A2, 2C9, 2C19 and 3A4 and the implications for herb-drug interaction

Abstract

Background: Studies have suggested an increasing practice of concurrent herb-drug consumption. One of the major clinical risks of such concomitant herb-drug use is pharmacokinetic herb-drug interaction (HDI). This is brought about by the ability of phytochemicals to inhibit or induce the activity of metabolic enzymes. The aim of this study was to investigate the potential of the crude aqueous extracts of three popular medicinal herbs used in South Africa to inhibit major cytochrome P450 (CYP) enzymes. Materials and Methods:The extracts of Bowiea volubilis, Spirostachys africana and Tulbaghia violacea were incubated with human liver microsomes (HLM) to monitor the phenacetin O-deethylation, diclofenac 4'-hydroxylation, S-mephenytoin 4'-hydroxylation and testosterone 6β-hydroxylation as respective probe reactions for CYP1A2, CYP2C9, CYP2C19 and CYP3A4. The inhibitory activity, where observed, was profiled against the extract concentration. Results: Extracts of Bowiea volubilis inhibited the metabolic activity of CYP1A2 and CYP3A4 with IC 50 values of 92.3 ± 5.5 g/mL and 8.1 ± 0.6 g/mL respectively. Similar observation with Spirostachys africana showed inhibitory activity against CYP1A2 and CYP3A4 with respective IC 50 values of 14.3 ± 0.6 g/mL and 47.4 ± 2.4 g/mL. Tulbaghia violacea demonstrated relatively weak inhibitory activity against CYP1A2 (767.4 ± 10.8 g/mL) and CYP2C9 (921 ± 15.3 g/mL). Conclusion:The results suggest the potential for HDI between the herbs and the substrates of the affected enzymes, if sufficient in vivo concentration is attained.

Flavokawain A inhibits Cytochrome P450 in in vitro metabolic and inhibitory investigations

“…Natural products owing to their low-toxicity have been increasingly developed and used as antitumor drugs (Fasinu et al, 2014). Regarding the efficacy and safety of the herbal medicines, several concerns have also been raised, such as biotransformation of the drug, drug-drug interaction et.al.…”

Impaired expression of testicular androgen receptor and collagen fibers in the testis of diabetic rats under HAART: the role of Hypoxis hemerocallidea

“…The use of medicinal herbs, a principal component of traditional medicine, predates the emergence of HIV/AIDS, and there is widespread consumption of herbal products for the management of HIV/AIDS either as complementary or alternative medicine [29].…”

“…However, the popularity of this plant rose tremendously following the increased [32] that is hydrolyzed into rooperol in the large intestine [33]. Pharmacokinetic studies have indicated that rooperol can be found in feces, and metabolites are found in the serum and urine as its glycosides, sulfates, mixed glucuronides and sulfuronides [29]. The glycoside has low toxicity and the corm containing it is also used as food [30] and has been well used for traditional and pharmaceutical purposes [31].…”

“…The search for herbal remedies has continued to grow due to its accessibility, relatively low cost and a perceived effectiveness. Consequently, there is wide spread of consumption of herbal products, including Hypoxis hemerocallidea (HH) for the management of HIV/AIDS either as complimentary or alternative medicine [29].…”

Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro

“…The increasing practice of co-administering herbal medicines with conventionally prescribed medications has raised considerably the risk of potential drug-herb interactions, especially in patients who already are on complex treatments involving narrow therapeutic index drugs [ 1 , 7 , 8 ]. Pharmacokinetic herb-drug interactions are one of the major risks caused by phytochemicals modulating the activities of enzymes that metabolize drugs, which subsequently affects their bioavailability [ 9 ]. For example, St. John's wort can decrease the steady state plasma concentrations of cyclosporine, midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon, and theophylline [ 10 ].…”