- a Université de Toulouse, UPS, UMR 152 Pharma-DEV, Université Toulouse 3, Faculté des Sciences Pharmaceutiques, F-31062 Toulouse Cedex 09, France
- b Institut de Recherche pour le Développement (IRD), UMR 152 Pharma-DEV, F-31062 Toulouse Cedex 09, France
- c CNRS, LCC (Laboratoire de Chimie de Coordination) UPR 8241, 31077 Toulouse Cedex 4, France
- d Université de Toulouse, UPS, INPT, 31077 Toulouse Cedex 4, France
- e Programa de Investigación en Biodiversidad Amazónica (PIBA). Instituto de Investigaciones de la Amazonía Peruana-IIAP, Av. Abelardo Quiñones km 4.5, Iquitos, Peru
- f Institut de Recherche pour le Développement (IRD), UMR 152 Pharma-DEV, Mission IRD, Casilla 18-1209, Lima, Peru
- Received 11 February 2015, Revised 5 May 2015, Accepted 5 May 2015, Available online 13 May 2015
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Abstract
Ethnopharmacological relevance
Pseudelephantopus spiralis (Less.) Cronquist is distributed in the Caribbean, Mesoamerica and Latin America. Preparations of the plant are traditionally used in Latin America for the treatment of various diseases including fever, malaria, and spleen or liver inflammations.
Materials and methods
Aerial parts of P. spiralis were extracted with either ethanol or distilled water. Seven hirsutinolide-type sesquiterpenoids were isolated: 8-acetyl-13-ethoxypiptocarphol (1), diacetylpiptocarphol (2), piptocarphins A (3), F (4) and D (5), (1S*,4R*,8S*,10R*)-1,4-epoxy-13-ethoxy-1,8,10-trihydroxygermacra-5E,7(11)-dien-6,12-olide (6), and piptocarphol (7). Extracts and isolated compounds (2, 3, 5–7) were screened for their in vitro antiplasmodial activity against the chloroquine-resistant Plasmodium falciparumstrain FcM29-Cameroon and antileishmanial activity against three stages of Leishmania infantum. Their cytotoxicities were also evaluated against healthy VERO cell lines and J774A.1 macrophages, the host cells of the Leishmania parasites in humans.
Results
Aqueous extracts showed a greater inhibitory effect than alcoholic extracts, with IC50 onP. falciparum of 3.0 µg/mL versus 21.1 µg/mL, and on L. infantum of 13.4 µg/mL versus >50 µg/mL. Both extracts were found to be cytotoxic to VERO cells (CC50<3 µg/mL). Sesquiterpene lactones 2 and 3 showed the best activity against both parasites but failed in selectivity. Carbon 8 hydroxylated hirsutinolides 5–7 presented the particularity of exhibiting two conformers observed in solution during extensive NMR analyses in CD3OD and UHPLC-MS. The presence of a hydroxyl function at C-8 decreased the activity of 5–7 on the two parasites and also on VERO cells.
Conclusion
The antiplasmodial activity displayed by the aqueous extract explains the traditional use of P. spiralis in the treatment of malaria. This activity seems to be attributable to the presence of sesquiterpene lactones 2 and 3, the most active against P. falciparum. Aqueous extract and compounds 2, 3 and 6 were also active against L. infantum but lacked in selectivity due to their cytotoxicity towards macrophages. Exploring the safety and antiplasmodial efficacy of this traditional remedy will require further toxicological and in vivo studies in the light of the cytotoxicity towards healthy cell lines displayed by the aqueous extract and compounds 2 and 3.
Graphical abstract
Keywords
- Pseudelephantopus spiralis;
- Sesquiterpene lactones;
- Hirsutinolides;
- Malaria;
- Leishmaniasis
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