Profile of herbal and dietary supplements induced liver injury in Latin America: A systematic review of published reports.

Hepatotoxicity related to HDS is a growing global health issue. We have undertaken a systematic review of published case reports and case series from LA from 1976 to 2020 to describe the clinical features of HDS related hepatotoxicity in this region. We search in PubMed, Web of Science, Scopus and specific LA databases according to PRISMA guidelines. Only HILI cases published in LA that met criteria for DILI definition were included. Duplicate records or reports that lacked relevant data that precluded establishing causality were excluded. Finally, 17 records (23 cases) were included in this review. Centella asiatica, Carthamus tinctorius, and Herbalife® were the most reported HDS culprit products, the main reason for HDS consumption was weight loss. The clinical characteristics of HDS hepatotoxicity in our study were compared to those of other studies in the USA, Europe and China showing a similar signature with predominance of young females, hepatocellular damage, a high rate of ALF and mortality, more frequent inadvertent re-challenge and chronic damage. This study underscores the challenge in causality assessment when multi-ingredients HDS are taken and the need for consistent publication practice when reporting hepatotoxicity cases due to HDS, to foster HDS liver safety particularly in LA.

Avaliação da qualidade microbiológica de cápsulas e chás de plantas utilizadas na assistência ao tratamento da obesidade / Microbiological quality evaluation of herbal capsules and teas to assist the treatment of obesity

O uso de plantas diuréticas e laxativas é uma alternativa medicamentosa para muitas pessoas que objetivam o emagrecimento com menores efeitos adversos. A avaliação microbiológica é um requisito essencial para a garantia de qualidade dos produtos. A finalidade deste trabalho foi avaliar a qualidade microbiológica de cápsulas e chás de alcachofra (Cynara scolymus L.), centella asiática (Hydrocotile asiatica L.), fucus (Fucus vesiculosus L.), e sene (Cassia acutifolia Delile), através da contagem de micro-organismos viáveis totais e pesquisa de patógenos. Na contagem de micro-organismos viáveis, os chás analisados foram aprovados, pois apesar de apresentarem uma carga microbiana elevada, esta se encontrava dentro das especificações, entretanto, 16,66% e 66,66% das cápsulas analisadas foram reprovadas por apresentaram quantidades superiores de bactérias e fungos, respectivamente. Na pesquisa de patógenos, 76% das amostras (88% dos chás e 58% das cápsulas) apresentaram um ou mais de um tipo de micro-organismo. Salmonella sp. esteve presente em 33% das amostras evidenciando a qualidade microbiológica insatisfatória dos produtos encontrados no mercado. Estes resultados demonstram a necessidade da realização do controle de qualidade tanto das matérias-primas vegetais, quanto dos produtos acabados, através do controle e fiscalização rigorosa, com adoção de medidas regulamentadoras e educativas.

The use of laxative and diuretic herbal drugs is an alternative therapy for many people looking for loosing weight with fewer side effects. The microbiological evaluation is an essential requirement for the quality assurance of products. This study aimed to evaluate the microbial quality of artichoke (Cynara scolymus L.), centella (Hydrocotile asiatica L.), fucus (Fucus vesiculosus L.), and Senna (Cassia acutifolia Delile) capsules and teas, by counting the total viable aerobic microorganisms and through tests for specified microorganisms. On the total viable aerobic microorganisms count, the teas analyzed were approved, because although they had a high microbial load, this was in accordance with the specifications, however 16.66% and 66.66% of the capsules analyzed were rejected because they presented higher amounts of bacteria and fungi, respectively. In relation to the tests for specified microorganisms, 76% of the samples (88% of the teas and 58% of the capsules) presented one or more than one type of microorganisms. Salmonella sp. was present in 33% of the samples, showing the unsatisfactory microbial quality of the products in the market. These results demonstrate the necessity of performing quality control both on herbal raw material and finished products, through a rigorous control and inspection, adopting regulatory and educational measures.

In vitro modulatory effects of Andrographis paniculata, Centella asiatica and Orthosiphon stamineus on cytochrome P450 2C19 (CYP2C19).

ETHNO PHARMACOLOGICAL RELEVANCE: Andrographis paniculata (AP), Centella asiatica (CA) and Orthosiphon stamineus (OS) are three popular herbs traditionally used worldwide. AP is known for the treatment of infections and diabetes and CA is good for wound healing and healthy skin while OS is usually consumed as tea to treat kidney and urinary disorders. Interaction of these herbs with human cytochrome P450 2C19 (CYP2C19), a major hepatic CYP isoform involved in metabolism of many clinical drugs has not been investigated to date. AIM OF THE STUDY: In this study, the modulatory effects of various extracts and major active constituents of AP, CA and OS on CYP2C19 activities were evaluated. MATERIALS AND METHODS: S-mephenytoin, the CYP2C19 substrate probe, was incubated in the presence or absence of AP, CA and OS components. The changes in the rate of metabolite (hydroxymephenytoin) formation were subsequently determined by a high-performance liquid chromatography (HPLC)-based enzyme assay to characterize the modulatory effects. RESULTS: Among the herbal extracts studied, AP ethanol extract and CA dichloromethane extract exhibited mixed type inhibition towards CYP2C19 with K(i) values of 67.1 and 16.4 µg/ml respectively; CA ethanol extract and OS petroleum ether extract competitively inhibited CYP2C19 activity (K(i)=39.6 and 41.5 µg/ml respectively). Eupatorin (a major active constituent of OS) was found to significantly inhibit CYP2C19 by mixed type inhibition (K(i)=7.1 µg/ml or 20.6 µM). CONCLUSIONS: It was observed that AP, CA and OS inhibited CYP2C19 activity with varying potency. While weak inhibitory effect was observed with AP, moderate to strong inhibition was observed with CA dichloromethane extract and eupatorin, the major OS constituent. Therefore care should be taken when these CA and OS components are co-administered with CYP2C19 substrates (such as omeprazole, proguanil, barbiturates, citalopram, and diazepam).

Rapid screening of commercially available herbal products for the inhibition of major human hepatic cytochrome P450 enzymes using the N-in-one cocktail.

Self-administration of complementary products concurrently with conventional medication is increasingly common. The potential for cytochrome P450 (CYP) inhibition requires investigation. The N-in-one assay with ten probe substrates for nine CYPs was used with human liver microsomes to investigate ten products. CYP inhibition was measured in a single liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis. Estimated IC(50)-values were determined for the extracts that produced significant inhibition (less than 100 microg ml(-1)). Inhibition of CYP2C19 by dong quai (IC(50) = 13.7-14.3 microg ml(-1) for the methanolic extract) and CYP2D6 by goldenseal (IC(50) = 6.7 and 6.3 microg ml(-1) for the aqueous and methanolic extracts, respectively), are of particular concern as the potential for adverse interactions is high. The inhibition of CYP2C8 by horsetail (IC(50) = 93 microg ml(-1) for the aqueous extract) requires further investigation, as the potential for concurrent use with products that require CYP2C8 for metabolism is significant. CYP3A4 inhibition varied depending on the probe reaction being monitored. The earlier reported findings of inhibition by black cohosh, goldenseal and gotu kola were confirmed. The present work has shown that the N-in-one cocktail is a rapid and reliable method that can be used as an initial screen to help prioritize products that require more detailed investigations and it can also be applied to monitor product variability.