Sphingolipidoses in Morocco: Chemical profiling for an affordable and rapid diagnosis strategy.

Sphingolipidoses are a group of metabolic diseases in which lysosomal hydrolases dysfunction disrupt normal sphingolipids' metabolism, leading to excess accumulation in cellular compartments and excretion in urine. These pathologies represent a significant burden among Moroccan population, for which an easy access to enzymatic assays and genetic tests is not guaranteed. Parallel analytical methods thus have to be developed for preliminary screening. In this study, 107 patients were addressed to the metabolic platform of the Marrakesh Faculty of Medicine for diagnosis confirmation. Thin-Layer Chromatography was used as a first step to perform chemical profiling of the patients' urinary lipids, allowing 36% of the patients to be efficiently oriented towards the adequate enzymatic assay. UPLC-MS/MS analyses of urinary sulfatides excreted in urines patient had been used to control the reliability of TLC analysis and to obtain more accurate information related to the sulfatides isoforms. This analytical process combining TLC with UPLC-MS/MS has enabled rapid and appropriate patient management in a reduced time and with reduced resources.

In vitro antidermatophytic activity of Otacanthus azureus (Linden) Ronse essential oil alone and in combination with azoles.

AIMS: We determined the chemical composition and investigated the antifungal activity of Otacanthus azureus (Linden) Ronse essential oil (EO) against a range of dermatophytes alone or in combination with azole antifungals. METHODS AND RESULTS: Aerial parts of the plant were steam-distilled and the obtained oil was analysed by gas chromatography/mass spectrometry and (1) H-NMR. It was shown to be largely composed of sesquiterpenes, with the main component being ß-copaen-4-α-ol. Using broth microdilution techniques, this oil was found to have remarkable in vitro antifungal activities. Minimum inhibitory concentrations as low as 4 µg ml(-1) were recorded. The analysis of the combined effect of the O. azureus EO with azoles using chequerboard assays revealed a synergism between the EO and ketoconazole, fluconazole or itraconazole against Trichophyton mentagrophytes. Notably, the O. azureus essential oil showed low cytotoxicity to VERO cells. CONCLUSIONS: The O. azureus essential oil alone or in combination with azoles is a promising antifungal agent in the treatment for human dermatomycoses caused by filamentous fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: There is much interest in the study of essential oils for the discovery of new antimicrobial drugs. This study has highlighted the antidermatophytic activity of the O. azureus EO.

Antimalarial activity of simalikalactone E, a new quassinoid from Quassia amara L. (Simaroubaceae).

We report the isolation and identification of a new quassinoid named simalikalactone E (SkE), extracted from a widely used Amazonian antimalarial remedy made out of Quassia amara L. (Simaroubaceae) leaves. This new molecule inhibited the growth of Plasmodium falciparum cultured in vitro by 50%, in the concentration range from 24 to 68 nM, independently of the strain sensitivity to chloroquine. We also showed that this compound was able to decrease gametocytemia with a 50% inhibitory concentration sevenfold lower than that of primaquine. SkE was found to be less toxic than simalikalactone D (SkD), another antimalarial quassinoid from Q. amara, and its cytotoxicity on mammalian cells was dependent on the cell line, displaying a good selectivity index when tested on nontumorogenic cells. In vivo, SkE inhibited murine malaria growth of Plasmodium vinckei petteri by 50% at 1 and 0.5 mg/kg of body weight/day, by the oral or intraperitoneal routes, respectively. The contribution of quassinoids as a source of antimalarial molecules needs therefore to be reconsidered.

Quassia amara L. (Simaroubaceae) leaf tea: effect of the growing stage and desiccation status on the antimalarial activity of a traditional preparation.

In French Guiana, Quassia amara L. (Simaroubaceae) leaf tea is a well-known widely used traditional antimalarial remedy. Impact of the vegetal sampling condition on in vivo and in vitro antimalarial activity was assessed. Traditional infusions were prepared with juvenile or mature leaves, both either fresh or dried. Results showed that growing stage and freshness of vegetal material exert a striking effect on antimalarial activity, both in vitro and in vivo. By far, leaf tea made from fresh juvenile (FJ) Quassia amara leaves was the most active. In vitro, active component (simalikalactone D) concentration correlates biological activities, although unexplained subtle variations were observed. In vivo, tea made with dried juvenile (DJ) leaves displays a peculiar behavior, meaning that some components may help simalikalactone D delivery or may be active in vivo only, therefore enhancing the expected curative effect of the traditional preparation.

From Tonic-cups to Bitter-cups: Kwasi bita beker from Suriname Determination, past and present use of an ancient galenic artefact.

In the main markets of Paramaribo (Suriname), many stands offer what is locally called "Bitter-cups", or "Kwasi bita beker", small footed-cups, roughly carved from a whitish wood. The use of these cups is strictly medicinal and it seems to be restricted to Suriname, as they are not found in neighbouring countries (Guyana, French Guiana). The aim of this study was to identify the botanical origin of Bitter-cups still in use in the Saramaka traditional medicine (as information from field people was controversial), and document the ethnopharmacology of this original galenical artefact. Microscopic and high performance liquid chromatography (HPLC) analyses were carried out on Bitter-cup, and anatomical criteria (marginal parenchyma band, size of intervessel and vessel-ray pits, rays width and rays composition, vessels clustering, frequency and size of parenchyma pits) together with HPLC profiles of the macerates showed that the wood cup was similar to Quassia amara L. (Simaroubaceae) wood. Ethnopharmacological investigation indicates that the use of these cups is simply due to the pharmacological properties attributed to "bitters", and is strongly linked to tradition and cultural attitudes. This study also emphasizes the long lasting use of these cups, now restricted to Suriname only, with almost no variation over one century.

Simalikalactone D is responsible for the antimalarial properties of an Amazonian traditional remedy made with Quassia amara L. (Simaroubaceae).

French Guiana (North-East Amazonia) records high malaria incidence rates. The traditional antimalarial remedy most widespread there is a simple tea made out from Quassia amara L. leaves (Simaroubaceae). This herbal tea displays an excellent antimalarial activity both in vitro and in vivo. A known quassinoid, simalikalactone D (SkD), was identified as the active compound, with an IC(50) value of 10nM against FcB1 Plasmodium falciparum chloroquine resistant strain in vitro. Lastly, it inhibits 50% of Plasmodium yoelii yoelii rodent malaria parasite at 3.7 mg/kg/day in vivo by oral route. These findings confirm the traditional use of this herbal tea.