In vitro antileishmanial and cytotoxicity activities of essential oils from Haplophyllum tuberculatum A. Juss leaves, stems and aerial parts

Background: Plants used for traditional medicine produce diverse and complex secondary metabolites exhibiting various medicinal properties. The medicinal plant Haplophyllum tuberculatum is used by native people against malaria and parasitic infections. Methods: In this study and in order to contribute for the search of new natural drugs for leishmaniasis, the essential oils of H. tuberculatum leaves, stems and aerial parts (leaves+stems) collected in two different periods, 2013 and 2015, and their components by GC/FID and GC/MS analyses were investigated. Those collected in 2013 were also re-analyzed two years later. The extracted oils were screened in vitro for anti-leishmanial activity on Leishmania mexicana mexicana (L.m.m.) promastigotes and cytotoxicity on the Chinese Hamster Ovary (CHO) cell line. Limonene (1.5 – 8%), its isomers (R- (+)-limonene and S-(-)-limonene), linalool and octanol were also tested. Results: Results showed that the chemical composition varied according to the year of collection. Though major compounds remain almost the same, qualitative and quantitative variations in the composition of the EOs can be observed between the two years of collection, with some minor compounds identified only in one type of samples. Variation in the composition were also observed in the re-analyzed volatile oils, showing stability concerns. The essential oils and R-(+)-limonene showed moderate anti-leishmanial activity. Their IC50 range from 6.48 to 50.28 μg/ml. Cytotoxicity assays for theses volatile extracts, R- (+)-limonene and S- (-)-limonene on CHO cells showed relatively potent cytotoxicity with a selectivity index <10. Their CC50 range from 27.79 to 82.56 μg/ml. Conclusions: The findings of the present study demonstrated that H. tuberculatum might not be considered as a natural source for production of new anti-leishmanial agents without further analyzing its eventual in vivo toxicity as well as that of major pure compounds

Vasorelaxant activity of essential oils from Croton zambesicus and some of their constituents.

In this study, we determined the vasorelaxant activity of essential oils of different samples of CROTON ZAMBESICUS collected in the same area in Benin at different periods and analysed their compositions by GC-FID and GC-MS. 68 compounds were identified among which 20 have not been described previously in this plant's essential oils. We observed quantitative differences among essential oils but all possess significant vasorelaxant activity on intact rat aortae contracted by KCl (IC (50) 5.6-11.8 µg/mL). This activity may, at least in part, be explained by the presence of vasorelaxant diterpenes such as ENT-18-hydroxy-trachyloban-3-one, isopimara-7,15-dien-3β-ol, and ENT-18-hydroxy-isopimar-7,15-dien-3β-ol, previously isolated from the dichloromethane extract of the leaves, but also to linalool (IC (50) 43.4 µg/mL) and particularly to caryophyllene oxide (IC (50) 2.5 µg/mL)

Article pubs.acs.org/Langmuir Domain Formation and Permeabilization Induced by the Saponin α‑Hederin and Its Aglycone Hederagenin in a Cholesterol-Containing

*S Supporting Information ABSTRACT: Saponins and triterpenic acids have been shown to be able to interact with lipid membranes and domains enriched with cholesterol (rafts). How saponins are able to modulate lipid phase separation in membranes and the role of the sugar chains for this activity is unknown. We demonstrate in a binary membrane model composed of DMPC/Chol (3:1 mol/mol) that the saponin α-hederin and its aglycone presenting no sugar chain, the triterpenic acid hederagenin, are able to induce the formation of lipid domains. We show on multilamellar vesicles (MLV), giant unilamellar vesicles (GUV), and supported planar bilayers (SPB) that the presence of sugar units on the sapogenin accelerates domain formation and increases the proportion of sterols within these domains. The domain shape is also influenced by the presence of sugars because α-hederin and hederagenin induce the formation of tubular and spherical domains, respectively. These highly curved structures should result from the induction of membrane curvature by both compounds. In addition to the formation of domains, α-hederin and hederagenin permeabilize GUV. The formation of membrane holes by α-hederin comes along with the accumulation of lipids into nonbilayer structures in SPB. This process might be responsible for the permeabilizing activity of both compounds. In LUV, permeabilization by α-hederin was sterol-dependent. The biological implications of our results and the mechanisms involved are discussed in relation t

Vascular activity of a natural diterpene isolated from Croton zambesicus and of a structurally similar synthetic trachylobane.

The aim of this study was to determine the vasorelaxant activity of a natural diterpene extracted from Croton zambesicus, ent-18-hydroxy-trachyloban-3-one (DT6), and a synthetic diterpene of similar structure, ent-trachyloban-14,15-dione (DT10) in rat aorta. DT6 and DT10 inhibited aorta contraction in a concentration-dependent manner. Both were more potent inhibitors of KCl-evoked contraction than noradrenaline-evoked contraction. Nitric oxide (NO) synthase inhibition did not significantly affect DT6 effect whereas it significantly decreased DT10 inhibitory potency. In fura-2 loaded aorta rings, DT10 simultaneously inhibited KCl-evoked contraction and cytosolic calcium increase in a concentration-dependent manner. Furthermore, DT10 significantly inhibited calcium channel current recorded by the patch-clamp technique in human neuroblastoma cells SH-SY5Y. However, despite potentiation of 8-bromo-cGMP-response, DT6 and DT10 as verapamil depressed acetylcholine-evoked relaxation, DT6 being the most potent, while only DT6 and DT10 depressed SNAP-evoked relaxation. In conclusion, these data suggest that vasorelaxant activity of diterpenes (DT) is associated with the blockade of L-type voltage-operated calcium channels. Inhibition of NO-dependent relaxation by DT could be related to a decrease in NO availability

N1,N2,N3-trisisopentenyl guanidine and N1,N2-diisopentenyl guanidine, two cytotoxic alkaloids from Alchornea cordifolia (Schumach.& Thonn.) Mull. Arg. (Euphorbiaceae) root barks.

This paper describes the purification of two guanidine alkaloids: NI, N2-diisopentenyl guanidine (DIPG) 1 and NI,N2,N3-trilsopentenyl guanidine (TIPG) 2 from Alchornea cordifolia root bark and reports their cytotoxic properties on cancer (HeLa, Me]-5, J774) and non cancer (WI 38) cells. TIPG showed the highest cytotoxicity with IC50 values from 0.7 to 14.3 mu g/mL (2.6 to 54.3 mu M) on the four cell lines while DIPG was much less active: IC50 45.8 and 97.6 mu g/mL (234.8 and 500.5 mu M) on Mel-5 and HeLa and > 512.8 mu M on J774 and WI 38. The results indicate that the cytotoxicity notably decreased with the loss of one isopentenyl substituent