Current issues and perspectives in herbal hepatotoxicity: a hidden epidemic

Abstract

Hepatic impairment resulting from the use of conventionaldrugs is widely acknowledged, yet there is a scant aware-ness of the potential hepatotoxicity of herbal medicines;nevertheless there is an increasing appeal of herbal medi-cines both for patients and health caregivers, only partiallyexplained by the return to the use of natural productsoccurring along with a cultural ecological movement in allindustrialized countries.Some herbs are well known for their direct hepatotox-icity (Teucrium chamaedrys, Senecio vulgaris, Morindacitrifolia, Ephedra sinica, Mentha pulegium, plants con-taining antraquinones, etc.) or for drug interferences(Panax ginseng, Citrus paradisi, Piper nigrum, Silybummarianum, Camellia sinensis, Monascus ruber, etc.). Formany herbs a sufficient knowledge of their pharmacody-namic and pharmacokinetic is lacking, this is particularlytrue when herbal products are used in combinations (as itoften happens in Oriental traditional medicines), making itdifficult to perform a causality assessment for the singleherbs involved. As suggested in the article by Licata et al.[1] herbal hepatotoxicity may become a hidden epidemic.Known herbal extracts with direct hepatotoxicity arevery few, nevertheless an unexpected idiosyncratic reactionis always possible, but physicians who are not true expertsin herbal medicine actually seem to overlook this importanttoxicological topic. This is similar with other impor-tant problems (herbal–drug interference, side effects, longterm toxicity) that consumers and health caregivers(including herbalists, naturopaths, dieticians, gym trainers,cosmeticians, masseurs, et al.) often ignore, thinking thatherb is synonymous with safety. We are completely inagreement with Licata et al. [1] that the safety of herbalproducts must be evaluated on the basis of existing scien-tific literature. In fact what is it that differentiates an herbalproduct from a conventional drug? A drug is consideredsafe and effective only if its preparation is standardized,and its safety and efficacy definitely assessed. Unfortu-nately, few of the used herbs are standardized by methodsthat can ensure a consistent product [1].Currently the main important and fast growing issue isherb–drug interactions: who can really estimate the realhepatotoxic risk of combining paracetamol with herbs thatcan interact with its metabolism? [2]. Because of theirbiological defence function, plant secondary metabolitesact by targeting and disrupting the cell membrane, bybinding and inhibiting specific proteins, or they adhere toor intercalate into RNA or DNA. Phytotherapeutics mayexhibit pharmacological effects by the synergistic orantagonistic interaction of many phytochemicals. Mechanis-tic reasons for interactions are bioavailability, interferencewith cellular transport processes, activation of pro-drugs ordeactivation of active compounds to inactive metabolites,action of synergistic partners at different points of the samesignalling cascade (multi-target effects) or inhibition ofbindingtotargetproteins. [3].Allofthese are important clueswhose definite biological effects are impossible to controlentirely.Another significant topic is the correct preparation of anextract: it is very important to prescribe herbal extractsundergoing a correct chain of controls in pharmacies orindustrial manufactures, avoiding use of self preparedremedies, or worse, bought on the internet directly from‘‘natural merchandisers,’’ which may skip any hygienic orauthority control [4].