Herbal medicines in Brazil: pharmacokinetic profile and potential herb-drug interactions

A plethora of active compounds found in herbal medicines can serve as substrate for enzymes involved in the metabolism of xenobiotics. When a medicinal plant is co-administered with a conventional drug and little or no information is known about the pharmacokinetics of the plant metabolites, there is an increased risk of potential herb-drug interactions. Moreover, genetic polymorphisms in a population may act to predispose individuals to adverse reactions. The use of herbal medicines is rapidly increasing in many countries, particularly Brazil where the vast biodiversity is a potential source of new and more affordable treatments for numerous conditions. Accordingly, the Brazilian Unified Public Health System (SUS) produced a list of 71 plant species of interest, which could be made available to the population in the near future. Physicians at SUS prescribe a number of essential drugs and should herbal medicines be added to this system the chance of herb-drug interactions further increases. A review of the effects of these medicinal plants on Phase 1 and Phase 2 metabolic mechanisms and the transporter P-glycoprotein was conducted. The results have shown that approximately half of these medicinal plants lack any pharmacokinetic data. Moreover, most of the studies carried out are in vitro. Only a few reports on herb-drug interactions with essential drugs prescribed by SUS were found, suggesting that very little attention is being given to the safety of herbal medicines. Here we have taken this information to discuss the potential interactions between herbal medicines and essential drugs prescribed to Brazilian patients whilst taking into account the most common polymorphisms present in the Brazilian population. A number of theoretical interactions are pinpointed but more pharmacokinetic studies and pharmacovigilance data are needed to ascertain their clinical significance

Potential Pharmacokinetic Interactions of Common Cardiovascular Drugs and Selected European and Latin American Herbal Medicines: A Scoping Review

Background: Herb–drug interactions are nowadays an important decision factor in many healthcare interventions. Patients with cardiovascular risk factors such as hyperlipidemia and hypertension are usually prescribed long-term treatments. We need more informed decision tools to direct future clinical research and decision making to avoid HDI occurrences in this group. Methods: A scoping review was conducted using data from online databases such as PUBMED, the National Library of Medicine, and the electronic Medicines Compendium. Included studies consisted of the reported effects on Phase 1/2 and P-glycoprotein of herbal medicines listed in the medicines agencies of Latin America and Europe and drugs used for cardiovascular conditions (statins, diuretics, beta blockers, calcium channel blockers, and ACE inhibitors). The cross tabulation of the results allowed for finding potential HDI. Results and conclusions: as per the preclinical data reviewed here, we encourage more clinical research on whether drugs with apparently very low interaction risk, such as pravastatin, nadolol, and nimodipine/nitrendipine, may help prevent HDI when statins, beta blockers, and calcium channel blockers, respectively, are prescribed for long-term treatments

In vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity

Many medicinal plants species from European -such as Artemisia absinthium, Equisetum arvense, Lamium album, Malva sylvestris, Morus nigra, Passiflora incarnata, Frangula purshiana, and Salix alba- as well as Latin American traditions -such as Libidibia ferrea, Bidens pilosa, Casearia sylvestris, Costus spicatus, Monteverdia ilicifolia, Persea americana, Schinus terebinthifolia, Solidago chilensis, Syzygium cumini, Handroanthus impetiginosus, and Vernonanthura phosphorica- are shortlisted by the Brazilian National Health System for future clinical use. However, they lack many data on their action upon some key ADME targets. In this study, we assess non-toxic concentrations (up to100 μg/ml) of their infusions for in vitro ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR). We further investigated the activation of human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells and the inhibition of Gamma-glutamyl transferase (GGT) in HepG2 cells. Our results demonstrate L. ferrea, C. sylvestris, M. ilicifolia, P. americana, S. terebinthifolia, S. cumini, V. phosphorica, E. arvense, P. incarnata, F. purshiana, and S. alba can significantly increase CYP3A4 mRNA gene expression in HepG2 cells. Only F. purshiana shown to do so likely via hPXR activation. P-gp activity was affected by L. ferrea, F. purshiana, S. terebinthifolia, and S. cumini. Total intracellular glutathione levels were significantly depleted by exposure to all extracts except S. alba and S. cumini This was accompanied by a lower GGT activity in the case of C. spicatus, P. americana, S. alba, and S. terebinthifolia, whilst L. ferrea, P. incarnata and F. purshiana increased it. Surprisingly, S. cumini aqueous extract drastically decreased GGT activity (−48%, p < 0.01). In conclusion, this preclinical study shows that the administration of some of these herbal medicines causes in vitro disturbances to key drug metabolism mechanisms. We recommend active pharmacovigilance for Libidibia ferrea (Mart.) L. P. Queiroz, Frangula purshiana Cooper, Schinus terebinthifolia Raddi, and Salix alba L. which were able to alter all targets in our preclinical study