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Eric Deharo - One of the best experts on this subject based on the ideXlab platform.
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Quassia "biopiracy" case and the Nagoya Protocol: A researcher's perspective.
Journal of Ethnopharmacology, 2017Co-Authors: Genevieve Bourdy, Valerie Jullian, Catherine Aubertin, Eric DeharoAbstract:Biopiracy accusations are common in the world of biodiversity research. At the end of 2015, a French NGO accused researchers from the Institut de Recherche pour le Developpement (IRD) of biopiracy. These researchers had applied for a patent for a natural bioactive molecule against malaria and cancer, the Simalikalactone E, isolated from Quassia amara L. (Simaroubaceae) leaves. This biopiracy allegation triggered a huge wave of attacks from the media and social networks, and vehement recrimination from political officials in French Guiana against researchers who have been accused of ethical misconduct, by stealing the traditional knowledge of indigenous people. These accusations were made in the contentious context of the ratification of the Nagoya Protocol in the frame of implementing the French law on biodiversity, nature and landscapes. So, in an atmosphere of heightened emotions it is crucial to understand the issues behind these accusations. We describe herein the genesis of our discovery, present the detractors’ arguments, and discuss the consequences of such biopiracy denunciations for scientific research. We also address our concerns about the gap between rhetoric and reality and the real impact of the Nagoya Protocol on biodiversity conservation.
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new findings on simalikalactone d an antimalarial compound from Quassia amara l simaroubaceae
Experimental Parasitology, 2012Co-Authors: Stephane Bertani, Emeline Houel, Genevieve Bourdy, Valerie Jullian, Alexis Valentin, Didier Stien, Eric DeharoAbstract:Abstract Quassia amara L. (Simaroubaceae) is a species widely used as tonic and is claimed to be an efficient antimalarial all over the Northern part of the Amazon basin. Quassinoid compound Simalikalactone D (SkD) has been shown to be one of the molecules responsible for the antiplasmodial activity of a watery preparation made out of juvenile fresh leaves of this plant. Because of its strong antimalarial activity, we decided to have a further insight of SkD pharmacological properties, alone or in association with classical antimalarials. At concentrations of up to 200 μM, we showed herein that SkD did not exert any apoptotic or necrotic activities in vitro on lymphoblastic cells. However, an antiproliferative effect was evident at concentrations higher than 45 nM. SkD was inefficient at inhibiting heme biomineralization and the new permeability pathways induced by the parasite in the host erythrocyte membrane. With respect to Plasmodium falciparum erythrocytic stages, SkD was almost inactive on earlier and later parasite stages, but potently active at the 30th h of parasite cycle when DNA replicates in mature trophozoites. In vitro combination studies with conventional antimalarial drugs showed that SkD synergizes with atovaquone (ATO). The activity of ATO on the Plasmodium mitochondrial membrane potential was enhanced by SkD, which on its own had a poor effect on this cellular parameter.
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picrasin k a new quassinoid from Quassia amara l simaroubaceae
Phytochemistry Letters, 2012Co-Authors: Nadja Cachet, Franciane Hoakwie, Marion Rivaud, Emeline Houel, Eric Deharo, Genevieve BourdyAbstract:Abstract A new quassinoid Picrasin K 1 was isolated from a decoction made of Quassia amara leaves, traditionally used in French Guyana to treat malaria. The structure and relative stereochemistry of 1 was determined through extensive NMR analysis. Picrasin K showed a low activity against Plasmodium falciparum in vitro (IC 50 = 8 μM), and a similar low activity on human cancerous cells line (IC 50 = 7 μM on MCF-7 cells line).
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quassinoid constituents of Quassia amara l simaroubaceae leaf herbal tea impact on its antimalarial activity and cytotoxicity
Planta Medica, 2010Co-Authors: Emeline Houel, Eric Deharo, Genevieve Bourdy, Valerie Jullian, Alexis Valentin, Stephane Bertani, Severine Chevalley, Didier StienAbstract:French Guiana records high malaria incidence rates. The traditional antimalarial remedy most widespread and still very much in use there is a tea made out from Quassia amara mature leaves. The antimalarial activity of this preparation was assessed [1] and in order to optimize the in vitro activity, different types of preparation have been realized and tested. The most active in vitro preparation is an infusion of fresh young leaves. It demonstrated a very good activity, in vitro as well as in vivo [2]. A known quassinoid, simalikalactone D (SkD), was identified as the active compound, with an IC50 value of 10 nM against FcB1 Plasmodium falciparum chloroquine resistant strain in vitro [3]. Our next objective was to assess whether it could be contemplated to recommend this young leaves tea for treatment against malaria, since it seemed from literature precedent that SkD was also cytotoxic to a number of cellular lineages [4,5]. We then characterized and quantified the antiparasitic and cytotoxic activities of all the constituents. Several quassinoids were isolated and characterized in the tea: SkD, quassin, neoquassin, and picrasins B, H, I (new) and J (new), SkD being responsible of both antiplasmodial activity and cytotoxicity. In addition, in the context of an antimalarial treatment, it appeared that the dose necessary for obtaining a curative antimalarial effect is close to the toxic dose of an SkD analogue, bruceantin. Prior to emitting a definitive conclusion, a clinical study in humans similar to the one done with bruceantin [6] should be performed. References: 1. Bertani, S. et al. (2005)J. Ethnopharmacol. 98:45–54. 2. Bertani, S. et al. (2007)J. Ethnopharmacol.111:40–42. 3. Bertani, S. et al. (2006)J. Ethnopharmacol.108:155–157. 4. Ozeki, A. et al. (1998)J. Nat. Prod. 61:776–780. 5. Xu, Z. et al. (2000)J. Nat. Prod. 63:1712–1715. 6. Bedikian, A.Y. et al. (1979) Cancer Treat. Rep. 63:1843–1847.
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quassinoid constituents of Quassia amara l leaf herbal tea impact on its antimalarial activity and cytotoxicity
Journal of Ethnopharmacology, 2009Co-Authors: Emeline Houel, Eric Deharo, Genevieve Bourdy, Stephane Bertani, Valerie Jullian, Alexis ValentinAbstract:Abstract Aim of the study Our objective was to assess whether it could be contemplated to recommend Quassia amara young leaf tea for treatment against malaria, and if yes, set up a standard protocol for preparing the herbal tea. Materials and methods The leaf tea was extracted with methylene chloride and the organic extract was fractionated with HPLC. Pure compounds were characterized and their in vitro cytotoxicity and antiplasmodial activity was determined. Results and discussion We discovered that antimalarial Quassia amara young leaf tea contains several quassinoids: simalikalactone D (SkD, 1 ), picrasin B ( 2 ), picrasin H ( 3 ), neoquassin ( 4 ), quassin ( 5 ), picrasin I ( 6 ) and picrasin J ( 7 ). These last two compounds are new. In addition, our experiments demonstrate that both biological activity and cytotoxicity of the remedy may be attributed solely to the presence of SkD. Conclusion In conclusion, this preparation should not be recommended for treatment of malaria until a clinical study in humans is performed with SkD.
Genevieve Bourdy - One of the best experts on this subject based on the ideXlab platform.
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Quassia "biopiracy" case and the Nagoya Protocol: A researcher's perspective.
Journal of Ethnopharmacology, 2017Co-Authors: Genevieve Bourdy, Valerie Jullian, Catherine Aubertin, Eric DeharoAbstract:Biopiracy accusations are common in the world of biodiversity research. At the end of 2015, a French NGO accused researchers from the Institut de Recherche pour le Developpement (IRD) of biopiracy. These researchers had applied for a patent for a natural bioactive molecule against malaria and cancer, the Simalikalactone E, isolated from Quassia amara L. (Simaroubaceae) leaves. This biopiracy allegation triggered a huge wave of attacks from the media and social networks, and vehement recrimination from political officials in French Guiana against researchers who have been accused of ethical misconduct, by stealing the traditional knowledge of indigenous people. These accusations were made in the contentious context of the ratification of the Nagoya Protocol in the frame of implementing the French law on biodiversity, nature and landscapes. So, in an atmosphere of heightened emotions it is crucial to understand the issues behind these accusations. We describe herein the genesis of our discovery, present the detractors’ arguments, and discuss the consequences of such biopiracy denunciations for scientific research. We also address our concerns about the gap between rhetoric and reality and the real impact of the Nagoya Protocol on biodiversity conservation.
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new findings on simalikalactone d an antimalarial compound from Quassia amara l simaroubaceae
Experimental Parasitology, 2012Co-Authors: Stephane Bertani, Emeline Houel, Genevieve Bourdy, Valerie Jullian, Alexis Valentin, Didier Stien, Eric DeharoAbstract:Abstract Quassia amara L. (Simaroubaceae) is a species widely used as tonic and is claimed to be an efficient antimalarial all over the Northern part of the Amazon basin. Quassinoid compound Simalikalactone D (SkD) has been shown to be one of the molecules responsible for the antiplasmodial activity of a watery preparation made out of juvenile fresh leaves of this plant. Because of its strong antimalarial activity, we decided to have a further insight of SkD pharmacological properties, alone or in association with classical antimalarials. At concentrations of up to 200 μM, we showed herein that SkD did not exert any apoptotic or necrotic activities in vitro on lymphoblastic cells. However, an antiproliferative effect was evident at concentrations higher than 45 nM. SkD was inefficient at inhibiting heme biomineralization and the new permeability pathways induced by the parasite in the host erythrocyte membrane. With respect to Plasmodium falciparum erythrocytic stages, SkD was almost inactive on earlier and later parasite stages, but potently active at the 30th h of parasite cycle when DNA replicates in mature trophozoites. In vitro combination studies with conventional antimalarial drugs showed that SkD synergizes with atovaquone (ATO). The activity of ATO on the Plasmodium mitochondrial membrane potential was enhanced by SkD, which on its own had a poor effect on this cellular parameter.
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picrasin k a new quassinoid from Quassia amara l simaroubaceae
Phytochemistry Letters, 2012Co-Authors: Nadja Cachet, Franciane Hoakwie, Marion Rivaud, Emeline Houel, Eric Deharo, Genevieve BourdyAbstract:Abstract A new quassinoid Picrasin K 1 was isolated from a decoction made of Quassia amara leaves, traditionally used in French Guyana to treat malaria. The structure and relative stereochemistry of 1 was determined through extensive NMR analysis. Picrasin K showed a low activity against Plasmodium falciparum in vitro (IC 50 = 8 μM), and a similar low activity on human cancerous cells line (IC 50 = 7 μM on MCF-7 cells line).
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quassinoid constituents of Quassia amara l simaroubaceae leaf herbal tea impact on its antimalarial activity and cytotoxicity
Planta Medica, 2010Co-Authors: Emeline Houel, Eric Deharo, Genevieve Bourdy, Valerie Jullian, Alexis Valentin, Stephane Bertani, Severine Chevalley, Didier StienAbstract:French Guiana records high malaria incidence rates. The traditional antimalarial remedy most widespread and still very much in use there is a tea made out from Quassia amara mature leaves. The antimalarial activity of this preparation was assessed [1] and in order to optimize the in vitro activity, different types of preparation have been realized and tested. The most active in vitro preparation is an infusion of fresh young leaves. It demonstrated a very good activity, in vitro as well as in vivo [2]. A known quassinoid, simalikalactone D (SkD), was identified as the active compound, with an IC50 value of 10 nM against FcB1 Plasmodium falciparum chloroquine resistant strain in vitro [3]. Our next objective was to assess whether it could be contemplated to recommend this young leaves tea for treatment against malaria, since it seemed from literature precedent that SkD was also cytotoxic to a number of cellular lineages [4,5]. We then characterized and quantified the antiparasitic and cytotoxic activities of all the constituents. Several quassinoids were isolated and characterized in the tea: SkD, quassin, neoquassin, and picrasins B, H, I (new) and J (new), SkD being responsible of both antiplasmodial activity and cytotoxicity. In addition, in the context of an antimalarial treatment, it appeared that the dose necessary for obtaining a curative antimalarial effect is close to the toxic dose of an SkD analogue, bruceantin. Prior to emitting a definitive conclusion, a clinical study in humans similar to the one done with bruceantin [6] should be performed. References: 1. Bertani, S. et al. (2005)J. Ethnopharmacol. 98:45–54. 2. Bertani, S. et al. (2007)J. Ethnopharmacol.111:40–42. 3. Bertani, S. et al. (2006)J. Ethnopharmacol.108:155–157. 4. Ozeki, A. et al. (1998)J. Nat. Prod. 61:776–780. 5. Xu, Z. et al. (2000)J. Nat. Prod. 63:1712–1715. 6. Bedikian, A.Y. et al. (1979) Cancer Treat. Rep. 63:1843–1847.
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quassinoid constituents of Quassia amara l leaf herbal tea impact on its antimalarial activity and cytotoxicity
Journal of Ethnopharmacology, 2009Co-Authors: Emeline Houel, Eric Deharo, Genevieve Bourdy, Stephane Bertani, Valerie Jullian, Alexis ValentinAbstract:Abstract Aim of the study Our objective was to assess whether it could be contemplated to recommend Quassia amara young leaf tea for treatment against malaria, and if yes, set up a standard protocol for preparing the herbal tea. Materials and methods The leaf tea was extracted with methylene chloride and the organic extract was fractionated with HPLC. Pure compounds were characterized and their in vitro cytotoxicity and antiplasmodial activity was determined. Results and discussion We discovered that antimalarial Quassia amara young leaf tea contains several quassinoids: simalikalactone D (SkD, 1 ), picrasin B ( 2 ), picrasin H ( 3 ), neoquassin ( 4 ), quassin ( 5 ), picrasin I ( 6 ) and picrasin J ( 7 ). These last two compounds are new. In addition, our experiments demonstrate that both biological activity and cytotoxicity of the remedy may be attributed solely to the presence of SkD. Conclusion In conclusion, this preparation should not be recommended for treatment of malaria until a clinical study in humans is performed with SkD.
Valerie Jullian - One of the best experts on this subject based on the ideXlab platform.
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Quassia "biopiracy" case and the Nagoya Protocol: A researcher's perspective.
Journal of Ethnopharmacology, 2017Co-Authors: Genevieve Bourdy, Valerie Jullian, Catherine Aubertin, Eric DeharoAbstract:Biopiracy accusations are common in the world of biodiversity research. At the end of 2015, a French NGO accused researchers from the Institut de Recherche pour le Developpement (IRD) of biopiracy. These researchers had applied for a patent for a natural bioactive molecule against malaria and cancer, the Simalikalactone E, isolated from Quassia amara L. (Simaroubaceae) leaves. This biopiracy allegation triggered a huge wave of attacks from the media and social networks, and vehement recrimination from political officials in French Guiana against researchers who have been accused of ethical misconduct, by stealing the traditional knowledge of indigenous people. These accusations were made in the contentious context of the ratification of the Nagoya Protocol in the frame of implementing the French law on biodiversity, nature and landscapes. So, in an atmosphere of heightened emotions it is crucial to understand the issues behind these accusations. We describe herein the genesis of our discovery, present the detractors’ arguments, and discuss the consequences of such biopiracy denunciations for scientific research. We also address our concerns about the gap between rhetoric and reality and the real impact of the Nagoya Protocol on biodiversity conservation.
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development and validation of liquid chromatography combined with tandem mass spectrometry methods for the quantitation of simalikalactone e in extracts of Quassia amara l and in mouse blood
Phytochemical Analysis, 2015Co-Authors: Valerie Jullian, Hong Luyen Le, Catherine Claparols, Marieke Vansteelandt, Mohamed HaddadAbstract:Introduction Simalikalactone E (SkE) from Quassia amara, has been proved to be a valuable anti-malarial and anti-cancer compound. As SkE is very scarce, methods of quantitation are needed in order to optimise its isolation process and to determine pharmacokinetic data. Objective To validate methods using liquid chromatography coupled to mass spectrometry for the quantitation of SkE in plant extracts and in biological fluids. Methods High- and ultrahigh-performance liquid chromatography (UHPLC) coupled to ion trap mass spectrometry (MS) with single ion monitoring detection and to triple quadrupole-linear ion trap tandem mass spectrometry with multiple reaction monitoring detection methods were developed. Validation procedure was realised according to the International Conference on Harmonisation guideline. Methanol extracts of dried Quassia amara leaves, and mouse-blood samples obtained after various routes of administration, were analysed for SkE. Results Methods were validated and gave similar results regarding the content of SkE expressed per kilogram of dry leaves in the traditional decoction (160 ± 12 mg/kg) and in the methanol extract (93 ± 2 mg/kg). The recovery of the analyte from mouse blood ranged from 80.7 to 119.8%. Simalikalactone E was only detected using UHPLC–MS/MS (0.2 ± 0.03 mg/L) in mouse blood after intravenous injection: none was detected following intraperitoneal or oral gavage administration of SkE. Conclusion The LC–MS methods were used for the quantitation of SkE in plant extracts and in mouse blood. These methods open the way for further protocol optimisation of SkE extraction and the determination of its pharmacokinetic data. Copyright © 2014 John Wiley & Sons, Ltd.
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new findings on simalikalactone d an antimalarial compound from Quassia amara l simaroubaceae
Experimental Parasitology, 2012Co-Authors: Stephane Bertani, Emeline Houel, Genevieve Bourdy, Valerie Jullian, Alexis Valentin, Didier Stien, Eric DeharoAbstract:Abstract Quassia amara L. (Simaroubaceae) is a species widely used as tonic and is claimed to be an efficient antimalarial all over the Northern part of the Amazon basin. Quassinoid compound Simalikalactone D (SkD) has been shown to be one of the molecules responsible for the antiplasmodial activity of a watery preparation made out of juvenile fresh leaves of this plant. Because of its strong antimalarial activity, we decided to have a further insight of SkD pharmacological properties, alone or in association with classical antimalarials. At concentrations of up to 200 μM, we showed herein that SkD did not exert any apoptotic or necrotic activities in vitro on lymphoblastic cells. However, an antiproliferative effect was evident at concentrations higher than 45 nM. SkD was inefficient at inhibiting heme biomineralization and the new permeability pathways induced by the parasite in the host erythrocyte membrane. With respect to Plasmodium falciparum erythrocytic stages, SkD was almost inactive on earlier and later parasite stages, but potently active at the 30th h of parasite cycle when DNA replicates in mature trophozoites. In vitro combination studies with conventional antimalarial drugs showed that SkD synergizes with atovaquone (ATO). The activity of ATO on the Plasmodium mitochondrial membrane potential was enhanced by SkD, which on its own had a poor effect on this cellular parameter.
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quassinoid constituents of Quassia amara l simaroubaceae leaf herbal tea impact on its antimalarial activity and cytotoxicity
Planta Medica, 2010Co-Authors: Emeline Houel, Eric Deharo, Genevieve Bourdy, Valerie Jullian, Alexis Valentin, Stephane Bertani, Severine Chevalley, Didier StienAbstract:French Guiana records high malaria incidence rates. The traditional antimalarial remedy most widespread and still very much in use there is a tea made out from Quassia amara mature leaves. The antimalarial activity of this preparation was assessed [1] and in order to optimize the in vitro activity, different types of preparation have been realized and tested. The most active in vitro preparation is an infusion of fresh young leaves. It demonstrated a very good activity, in vitro as well as in vivo [2]. A known quassinoid, simalikalactone D (SkD), was identified as the active compound, with an IC50 value of 10 nM against FcB1 Plasmodium falciparum chloroquine resistant strain in vitro [3]. Our next objective was to assess whether it could be contemplated to recommend this young leaves tea for treatment against malaria, since it seemed from literature precedent that SkD was also cytotoxic to a number of cellular lineages [4,5]. We then characterized and quantified the antiparasitic and cytotoxic activities of all the constituents. Several quassinoids were isolated and characterized in the tea: SkD, quassin, neoquassin, and picrasins B, H, I (new) and J (new), SkD being responsible of both antiplasmodial activity and cytotoxicity. In addition, in the context of an antimalarial treatment, it appeared that the dose necessary for obtaining a curative antimalarial effect is close to the toxic dose of an SkD analogue, bruceantin. Prior to emitting a definitive conclusion, a clinical study in humans similar to the one done with bruceantin [6] should be performed. References: 1. Bertani, S. et al. (2005)J. Ethnopharmacol. 98:45–54. 2. Bertani, S. et al. (2007)J. Ethnopharmacol.111:40–42. 3. Bertani, S. et al. (2006)J. Ethnopharmacol.108:155–157. 4. Ozeki, A. et al. (1998)J. Nat. Prod. 61:776–780. 5. Xu, Z. et al. (2000)J. Nat. Prod. 63:1712–1715. 6. Bedikian, A.Y. et al. (1979) Cancer Treat. Rep. 63:1843–1847.
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quassinoid constituents of Quassia amara l leaf herbal tea impact on its antimalarial activity and cytotoxicity
Journal of Ethnopharmacology, 2009Co-Authors: Emeline Houel, Eric Deharo, Genevieve Bourdy, Stephane Bertani, Valerie Jullian, Alexis ValentinAbstract:Abstract Aim of the study Our objective was to assess whether it could be contemplated to recommend Quassia amara young leaf tea for treatment against malaria, and if yes, set up a standard protocol for preparing the herbal tea. Materials and methods The leaf tea was extracted with methylene chloride and the organic extract was fractionated with HPLC. Pure compounds were characterized and their in vitro cytotoxicity and antiplasmodial activity was determined. Results and discussion We discovered that antimalarial Quassia amara young leaf tea contains several quassinoids: simalikalactone D (SkD, 1 ), picrasin B ( 2 ), picrasin H ( 3 ), neoquassin ( 4 ), quassin ( 5 ), picrasin I ( 6 ) and picrasin J ( 7 ). These last two compounds are new. In addition, our experiments demonstrate that both biological activity and cytotoxicity of the remedy may be attributed solely to the presence of SkD. Conclusion In conclusion, this preparation should not be recommended for treatment of malaria until a clinical study in humans is performed with SkD.
Didier Stien - One of the best experts on this subject based on the ideXlab platform.
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new findings on simalikalactone d an antimalarial compound from Quassia amara l simaroubaceae
Experimental Parasitology, 2012Co-Authors: Stephane Bertani, Emeline Houel, Genevieve Bourdy, Valerie Jullian, Alexis Valentin, Didier Stien, Eric DeharoAbstract:Abstract Quassia amara L. (Simaroubaceae) is a species widely used as tonic and is claimed to be an efficient antimalarial all over the Northern part of the Amazon basin. Quassinoid compound Simalikalactone D (SkD) has been shown to be one of the molecules responsible for the antiplasmodial activity of a watery preparation made out of juvenile fresh leaves of this plant. Because of its strong antimalarial activity, we decided to have a further insight of SkD pharmacological properties, alone or in association with classical antimalarials. At concentrations of up to 200 μM, we showed herein that SkD did not exert any apoptotic or necrotic activities in vitro on lymphoblastic cells. However, an antiproliferative effect was evident at concentrations higher than 45 nM. SkD was inefficient at inhibiting heme biomineralization and the new permeability pathways induced by the parasite in the host erythrocyte membrane. With respect to Plasmodium falciparum erythrocytic stages, SkD was almost inactive on earlier and later parasite stages, but potently active at the 30th h of parasite cycle when DNA replicates in mature trophozoites. In vitro combination studies with conventional antimalarial drugs showed that SkD synergizes with atovaquone (ATO). The activity of ATO on the Plasmodium mitochondrial membrane potential was enhanced by SkD, which on its own had a poor effect on this cellular parameter.
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quassinoid constituents of Quassia amara l simaroubaceae leaf herbal tea impact on its antimalarial activity and cytotoxicity
Planta Medica, 2010Co-Authors: Emeline Houel, Eric Deharo, Genevieve Bourdy, Valerie Jullian, Alexis Valentin, Stephane Bertani, Severine Chevalley, Didier StienAbstract:French Guiana records high malaria incidence rates. The traditional antimalarial remedy most widespread and still very much in use there is a tea made out from Quassia amara mature leaves. The antimalarial activity of this preparation was assessed [1] and in order to optimize the in vitro activity, different types of preparation have been realized and tested. The most active in vitro preparation is an infusion of fresh young leaves. It demonstrated a very good activity, in vitro as well as in vivo [2]. A known quassinoid, simalikalactone D (SkD), was identified as the active compound, with an IC50 value of 10 nM against FcB1 Plasmodium falciparum chloroquine resistant strain in vitro [3]. Our next objective was to assess whether it could be contemplated to recommend this young leaves tea for treatment against malaria, since it seemed from literature precedent that SkD was also cytotoxic to a number of cellular lineages [4,5]. We then characterized and quantified the antiparasitic and cytotoxic activities of all the constituents. Several quassinoids were isolated and characterized in the tea: SkD, quassin, neoquassin, and picrasins B, H, I (new) and J (new), SkD being responsible of both antiplasmodial activity and cytotoxicity. In addition, in the context of an antimalarial treatment, it appeared that the dose necessary for obtaining a curative antimalarial effect is close to the toxic dose of an SkD analogue, bruceantin. Prior to emitting a definitive conclusion, a clinical study in humans similar to the one done with bruceantin [6] should be performed. References: 1. Bertani, S. et al. (2005)J. Ethnopharmacol. 98:45–54. 2. Bertani, S. et al. (2007)J. Ethnopharmacol.111:40–42. 3. Bertani, S. et al. (2006)J. Ethnopharmacol.108:155–157. 4. Ozeki, A. et al. (1998)J. Nat. Prod. 61:776–780. 5. Xu, Z. et al. (2000)J. Nat. Prod. 63:1712–1715. 6. Bedikian, A.Y. et al. (1979) Cancer Treat. Rep. 63:1843–1847.
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antimalarial activity of simalikalactone e a new quassinoid from Quassia amara l simaroubaceae
Antimicrobial Agents and Chemotherapy, 2009Co-Authors: Nadja Cachet, Franciane Hoakwie, Eric Deharo, Genevieve Bourdy, Stephane Bertani, Didier StienAbstract: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.
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Quassia amara l simaroubaceae leaf tea effect of the growing stage and desiccation status on the antimalarial activity of a traditional preparation
Journal of Ethnopharmacology, 2007Co-Authors: Stephane Bertani, Emeline Houel, Genevieve Bourdy, Valerie Jullian, Didier Stien, Irene Landau, Eric DeharoAbstract: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.
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simalikalactone d is responsible for the antimalarial properties of an amazonian traditional remedy made with Quassia amara l simaroubaceae
Journal of Ethnopharmacology, 2006Co-Authors: Stephane Bertani, Emeline Houel, Genevieve Bourdy, Valerie Jullian, Didier Stien, Lionel Chevolot, Giovanni Garavito, Eric DeharoAbstract:Abstract 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 10 nM 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.
Emeline Houel - One of the best experts on this subject based on the ideXlab platform.
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new findings on simalikalactone d an antimalarial compound from Quassia amara l simaroubaceae
Experimental Parasitology, 2012Co-Authors: Stephane Bertani, Emeline Houel, Genevieve Bourdy, Valerie Jullian, Alexis Valentin, Didier Stien, Eric DeharoAbstract:Abstract Quassia amara L. (Simaroubaceae) is a species widely used as tonic and is claimed to be an efficient antimalarial all over the Northern part of the Amazon basin. Quassinoid compound Simalikalactone D (SkD) has been shown to be one of the molecules responsible for the antiplasmodial activity of a watery preparation made out of juvenile fresh leaves of this plant. Because of its strong antimalarial activity, we decided to have a further insight of SkD pharmacological properties, alone or in association with classical antimalarials. At concentrations of up to 200 μM, we showed herein that SkD did not exert any apoptotic or necrotic activities in vitro on lymphoblastic cells. However, an antiproliferative effect was evident at concentrations higher than 45 nM. SkD was inefficient at inhibiting heme biomineralization and the new permeability pathways induced by the parasite in the host erythrocyte membrane. With respect to Plasmodium falciparum erythrocytic stages, SkD was almost inactive on earlier and later parasite stages, but potently active at the 30th h of parasite cycle when DNA replicates in mature trophozoites. In vitro combination studies with conventional antimalarial drugs showed that SkD synergizes with atovaquone (ATO). The activity of ATO on the Plasmodium mitochondrial membrane potential was enhanced by SkD, which on its own had a poor effect on this cellular parameter.
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picrasin k a new quassinoid from Quassia amara l simaroubaceae
Phytochemistry Letters, 2012Co-Authors: Nadja Cachet, Franciane Hoakwie, Marion Rivaud, Emeline Houel, Eric Deharo, Genevieve BourdyAbstract:Abstract A new quassinoid Picrasin K 1 was isolated from a decoction made of Quassia amara leaves, traditionally used in French Guyana to treat malaria. The structure and relative stereochemistry of 1 was determined through extensive NMR analysis. Picrasin K showed a low activity against Plasmodium falciparum in vitro (IC 50 = 8 μM), and a similar low activity on human cancerous cells line (IC 50 = 7 μM on MCF-7 cells line).
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etude de substances bioactives issues de la flore amazonienne analyse de preparations phytotherapeutiques a base de Quassia amara l simaroubaceae et de psidium acutangulum dc myrtaceae utilisees en guyane francaise pour une indication antipaludique i
2011Co-Authors: Emeline HouelAbstract:L’objectif du travail effectue etait la recherche de nouvelles substances actives d’origine vegetale, presentant soit une activite antiplasmodiale soit une activite antifongique. Cette etude a ete menee suivant deux strategies differentes: l’etude de remedes traditionnels antipaludiques identifies suite a des enquetes ethnopharmacologiques, et la mise en evidence des proprietes antifongiques d’huiles essentielles grâce a une strategie bioinspiree. La premiere partie du travail a permis de mettre en evidence le role d’un quassinoide connu, la simalikalactone D, dans l’activite antipaludique d’une tisane de jeunes feuilles fraiches de Quassia amara L. (Simaroubaceae). Dans le cas de la decoction de rameaux de Psidium acutangulum DC. (Myrtaceae), c’est cette fois un melange de flavonoides glycosyles qui est responsable de l’activite du remede. Dans le cadre de la recherche de nouvelles substances antifongiques, le criblage effectue a permis d’identifier de nombreuses huiles essentielles presentant des activites interessantes, validant ainsi la demarche bioinspiree retenue dans ce cas. L’huile essentielle d’Otacanthus azureus (Linden) Ronse a en particulier demontre une activite remarquable, a la fois seule et en combinaison avec des antifongiques azoles. Enfin, l’etude metabolomique de la composition des huiles essentielles a permis de mettre au point un outil pouvant orienter la selection des huiles en fonction des donnees obtenues en GC/MS dans l’optique de la recherche de nouvelles substances antifongiques. Ce travail demontre donc la validite des strategies retenues – ethnopharmacologie et bioinspiration – dans la recherche de nouvelles substances bioactives.
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quassinoid constituents of Quassia amara l simaroubaceae leaf herbal tea impact on its antimalarial activity and cytotoxicity
Planta Medica, 2010Co-Authors: Emeline Houel, Eric Deharo, Genevieve Bourdy, Valerie Jullian, Alexis Valentin, Stephane Bertani, Severine Chevalley, Didier StienAbstract:French Guiana records high malaria incidence rates. The traditional antimalarial remedy most widespread and still very much in use there is a tea made out from Quassia amara mature leaves. The antimalarial activity of this preparation was assessed [1] and in order to optimize the in vitro activity, different types of preparation have been realized and tested. The most active in vitro preparation is an infusion of fresh young leaves. It demonstrated a very good activity, in vitro as well as in vivo [2]. A known quassinoid, simalikalactone D (SkD), was identified as the active compound, with an IC50 value of 10 nM against FcB1 Plasmodium falciparum chloroquine resistant strain in vitro [3]. Our next objective was to assess whether it could be contemplated to recommend this young leaves tea for treatment against malaria, since it seemed from literature precedent that SkD was also cytotoxic to a number of cellular lineages [4,5]. We then characterized and quantified the antiparasitic and cytotoxic activities of all the constituents. Several quassinoids were isolated and characterized in the tea: SkD, quassin, neoquassin, and picrasins B, H, I (new) and J (new), SkD being responsible of both antiplasmodial activity and cytotoxicity. In addition, in the context of an antimalarial treatment, it appeared that the dose necessary for obtaining a curative antimalarial effect is close to the toxic dose of an SkD analogue, bruceantin. Prior to emitting a definitive conclusion, a clinical study in humans similar to the one done with bruceantin [6] should be performed. References: 1. Bertani, S. et al. (2005)J. Ethnopharmacol. 98:45–54. 2. Bertani, S. et al. (2007)J. Ethnopharmacol.111:40–42. 3. Bertani, S. et al. (2006)J. Ethnopharmacol.108:155–157. 4. Ozeki, A. et al. (1998)J. Nat. Prod. 61:776–780. 5. Xu, Z. et al. (2000)J. Nat. Prod. 63:1712–1715. 6. Bedikian, A.Y. et al. (1979) Cancer Treat. Rep. 63:1843–1847.
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quassinoid constituents of Quassia amara l leaf herbal tea impact on its antimalarial activity and cytotoxicity
Journal of Ethnopharmacology, 2009Co-Authors: Emeline Houel, Eric Deharo, Genevieve Bourdy, Stephane Bertani, Valerie Jullian, Alexis ValentinAbstract:Abstract Aim of the study Our objective was to assess whether it could be contemplated to recommend Quassia amara young leaf tea for treatment against malaria, and if yes, set up a standard protocol for preparing the herbal tea. Materials and methods The leaf tea was extracted with methylene chloride and the organic extract was fractionated with HPLC. Pure compounds were characterized and their in vitro cytotoxicity and antiplasmodial activity was determined. Results and discussion We discovered that antimalarial Quassia amara young leaf tea contains several quassinoids: simalikalactone D (SkD, 1 ), picrasin B ( 2 ), picrasin H ( 3 ), neoquassin ( 4 ), quassin ( 5 ), picrasin I ( 6 ) and picrasin J ( 7 ). These last two compounds are new. In addition, our experiments demonstrate that both biological activity and cytotoxicity of the remedy may be attributed solely to the presence of SkD. Conclusion In conclusion, this preparation should not be recommended for treatment of malaria until a clinical study in humans is performed with SkD.
