Leishmaniasis is a neglected tropical disease that still infects thousands of people per year throughout the world. The occurrence of resistance against major treatments for this disease causes a healthcare burden in low-income countries. Eugenol is a phenylpropanoid that has shown in vitro antileishmanial activity against Leishmania mexicana mexicana (Lmm) promastigotes with an IC₅₀ of 2.72 µg/mL and a high selectivity index. Its specific mechanism of action has yet to be studied. We prepared large unilamellar vesicles (LUVs), mimicking Lmm membranes, and observed that eugenol induced an increase in membrane permeability and a decrease in membrane fluidity at concentrations much higher than IC₅₀. The effect of eugenol was similar to the current therapeutic antibiotic, amphotericin B, although the latter was effective at lower concentrations than eugenol. However, unlike amphotericin B, eugenol also affected the permeability of LUVs without sterol. Its effect on the membrane fluidity of Lmm showed that at high concentrations (≥22.5× IC₅₀), eugenol increased membrane fluidity by 20–30%, while no effect was observed at lower concentrations. Furthermore, at concentrations below 10× IC₅₀, a decrease in metabolic activity associated with the maintenance of membrane integrity revealed a leishmaniostatic effect after 24 h of incubation with Lmm promastigotes. While acidocalcisomes distribution and abundance revealed by Trypanosoma brucei vacuolar H⁺ pyrophosphatase (TbVP1) immunolabeling was not modified by eugenol, a dose-dependent decrease of lipid droplets assessed by the Nile Red assay was observed. We hereby demonstrate that the antileishmanial activity of eugenol might not directly involve plasma membrane sterols such as ergosterol, but rather target the lipid storage of Lmm.

The term cosmetopoeia refers to the use of plants in folks’ cosmetics. The aerial parts of Bidens pilosa L., the leaves of Calophyllum inophyllum L. and the fruits of Fagraea berteroana A.Gray ex Benth are traditionally used in French Polynesia for hair and skin care. During the hair cycle, dermal papilla cells and their interaction with epithelial cells are essential to promote hair follicle elongation. The aim of our investigations was the identification of metabolites from these three plants and chemical families responsible for their hair growth activity. A bioactivity-based molecular network was produced by mapping the correlation between features obtained from LC-MS/MS data and dermal papilla cell proliferation, using the Pearson correlation coefficient. The analyses pointed out glycosylated flavonols and phenolic acids from B. pilosa and C. inophyllum, along with C-flavonoids, iridoids and secoiridoids from F. berteroana, as potential bioactive molecules involved in the proliferation of hair follicle dermal papilla cells. Our results highlight the metabolites of the plant species potentially involved in the induction of hair follicle growth and support the traditional uses of these plants in hair care.

Terminalia leiocarpa is a medicinal plant widely used in ethnoveterinary medicine to treat digestive parasitosis whose extracts were shown to be active against gastrointestinal nematodes of domestic ruminants. The objective of our study was to identify compounds responsible for this activity. Column fractionation was performed, and the activity of the fractions was assessed in vitro on Haemonchus contortus and Caenorhabditis elegans as well as their cytotoxicity on WI38 fibroblasts. Two fractions were the most active on both nematode models and less cytotoxic. LC-MS/MS analysis and manual dereplication coupled to molecular networking allowed identification of the main compounds: ellagic acid and derivatives, gallic acid, astragalin, rutin, quinic acid, and fructose. Other potentially identified compounds such as shikimic acid, 2,3-(S)-hexahydroxydiphenoyl-D-glucose or an isomer, quercetin-3-O-(6-O-galloyl)-β-D-galactopyranoside or an isomer, and a trihydroxylated triterpenoid bearing a sugar as rosamultin are reported in this plant for the first time. Evaluation of the anthelmintic activity of the available major compounds showed that ellagic and gallic acids were the most effective in inhibiting the viability of C. elegans. Their quantification in fractions 8 and 9 indicated the presence of about 8.6 and 7.1 µg/mg ellagic acid and about 9.6 and 2.0 µg/mg gallic acid respectively. These concentrations are not sufficient to justify the activity observed. Ellagic acid derivatives and other compounds that were found to be positively correlated with the anthelmintic activity of the fractions may have additive or synergistic effects when combined, but other unidentified compounds could also be implicated in the observed activity.

Hair loss is becoming increasingly prevalent as dietary and living habits change. The search for natural products to limit hair loss has led to tapping into traditional cosmetic knowledge. We studied three plants of the Polynesian cosmetopoeia, Bidens pilosa, Calophyllum inophyllum and Fagraea berteroana, to determine their ability to promote hair growth. Their chemical content was characterized by liquid chromatography coupled to mass spectrometry (LC-MS). Their proliferative activity on dermal papilla cells (DPCs) was assessed via MTT assay and molecular targets were evaluated by RT-qPCR analysis of seven factors involved in the modulation of the hair cycle, CCND1, LEF1, DKK1, WNT5A PPARD, TGFΒ1, PPARD and RSPO2. Our results show that our extracts significantly increased proliferation of dermal papilla cells. Furthermore, LC-MS/MS analysis revealed a diversity of molecules, flavonoids, iridoids and organic acids, some known for hair-inducing properties. Finally, specific extracts and fractions of all three plants either upregulated CCND1, LEF1 and PPARD involved in stimulating hair follicle proliferation and/or lowered the gene expression levels of hair growth inhibiting factors, DKK1 and TGFB1. Our findings suggest that extracts from B. pilosa, C. inophyllum and F. berteroana are interesting candidates to stimulate hair growth.

Trypanosomiasis is a parasitic disease for which new treatments are needed due to the frequent occurrence of adverse side effects of current available drugs. Natural compounds found in traditionally used plants offer opportunities to discover innovative compounds that could prove pivotal to antitrypanosomal drug development. 3-O-p-(Z/E)-coumaroyltormentic acids (CTA) were isolated first from the West Africa-native tree Vitellaria paradoxa and have demonstrated quite selective in vitro and in vivo antitrypanosomal activity, despite the unknown mode of action. In this study, a metabolomics analysis using the data from both LC-HR-MS and ¹H-NMR described CTA's effects on Trypanosoma brucei after 3 h exposure under 5 or 10 x EC₅₀. Our study shows CTA's activity impacted tryptophan metabolism and reveals potential targets in different branches of this metabolism. Our results demonstrate a likely presence of enzymes dedicated to tryptophan, like a tryptophan aminotransferase, tryptophan 2,3-dioxygenase and/or indoleamine 2,3-dioxygenase, and other enzymes of the kynurenine pathway, despite the absence of their description thus far in this species. These data further implicate that CTA's toxic effect on the tryptophan metabolism may be attributed to the decrease of the intracellular level of essential aspartate, resulting from inhibition of its aminotransferase. In resume, our study shines light on the likelihood of the tryptophan metabolism pathway presenting innovative targets toward the development of antitrypanosomal drugs. These require confirmation through functional and enzymatic studies.