Evaluation of herb-drug interactions in Nigeria with a focus on medicinal plants used in diabetes management

Studies have shown an increasing use of herbal medicines alongside conventional drugs by patients in their disease management especially for chronic diseases, with the attendant risks of herb-drug interactions. In order to forestall this, adequate information about the pharmacological and toxicological profile of herbal medicines and how these would in turn affect the bioavailability of the co-administered drug is required. To evaluate potential herb-drug interactions that could occur in diabetes management in Nigeria- (a) An assessment of available data on the pharmacological and toxicological effects of plants used in diabetes management was conducted as a means of mapping those with identified potential risks for herb-drug interactions; (b) A field work study was carried out in different localities in Nigeria to identify potential pharmacokinetic interactions based on the prescription drugs and herbal medicines co-administered by diabetic patients; and (c) Experimental analysis of plant samples collected during the field work was done to assess their effects on known cell detoxification mechanisms and pharmacokinetic parameters. The results of the research have confirmed the continued use of a wide range of medicinal plants in diabetes management, many of which have not been thoroughly investigated. In addition, 50% of diabetic patients visiting healthcare facilities in Nigeria routinely manage their diabetes or existing co-morbidities with herbal medicines alongside prescription drugs. Even more worrying is the frequent use of unlabeled herbal preparations which would constitute a huge challenge in the proper identification of herb-drug interactions when they occur. Based on previously available data and the experimental results of this research, a number of these herbal medicines have been identified as having overlapping interactions with prescription drugs. There is therefore a need for better regulation of herbal medicine use alongside pharmacovigilance monitoring in Nigeria in order to forestall the occurrence of clinically relevant untoward herb-drug interactions

In Vitro Modulation of Glibenclamide Transport by P-glycoprotein Inhibitory Antidiabetic African Plant Extracts (1)

The rise of diabetes incidence in Nigeria enhances the use of popular remedies that may interact with conventional therapies. The aqueous extracts of 27 popular Nigerian “antidiabetic” plants were tested for their in vitro effects on glutathione levels within HepG2 cells, P-glycoprotein (P-gp)-mediated Rh-123 efflux activity in Caco-2 vincristine-resistant cells, and modulation of glibenclamide transport in Caco-2 monolayers. The extract from Ximenia americana significantly depleted intracellular glutathione at 100 µg/mL similarly to the reference buthionine sulphoximine (p < 0.05). Other 10 extracts raised glutathione levels. Eight extracts inhibiting P-gp efflux in a concentration-dependent manner (p < 0.01) were selected for further evaluation in a bi-directional transport model across Caco-2 monolayers: Annona senegalensis, Bridellia ferruginea, Cassytha filiformis, Daniellia ogea, Khaya ivorensis, Syzygium guineense, Terminalia avicennioides, and X. americana. When interferences in paracellular transport were discarded, only 3 of them may be modulating the efflux ratio of glibenclamide (efflux ratio: 2.65 ± 0.13) in the same manner the reference drug verapamil (efflux ratio: 1.14 ± 0.25, p < 0.01) does: Syzygium guineense (efflux ratio: 1.70 ± 0.23, p < 0.01), Terminalia avicennioides (efflux ratio: 1.80 ± 0.25, p < 0.05), and X. americana (efflux ratio: 1.66 ± 0.10, p < 0.01). HPLC-UV analyses for P-gp inhibitors in these extracts revealed several phenolic compounds such as rutin, gallic acid, and ellagic acid reported to decrease P-gp expression and/or directly modify its function. In conclusion, some popular herbal medicines used by Nigerian diabetic patients are here shown to potentially affect glibenclamide absorption at concentrations that could be reached in the intestinal tract