Study about an anti-inflammatory natural diterpenes family

Andrographis paniculata est une échinacée d’origine asiatique utilisée depuis plus de deux milles ans en médecine traditionnelle asiatique. Ses activités anti-bactériennes, anti-virales et hépatoprotectrices, entre autre, en ont fait un sujet d’étude important depuis les trente dernières années. Cette plante est principalement constituée de diterpènes de série ent-labdanes, dont le composé majoritaire est l’andrographolide, une lactone diterpénique, qui a montré des propriétés anti-inflammatoires sur la voie NFB. C’est dans le but de comprendre et d’améliorer les activités anti-inflammatoires des composés issus de la plante que nous avons envisagé l’étude de la famille des andrographolides. Une étude qualitative d’extraits issus de compléments alimentaires a permis d’obtenir trois composés naturels, qui ont été pharmacomodulés chimiquement. De plus, une méthode quantitative de quatre extraits bruts a permis de déterminer la concentration des trois composés naturels isolés dans chaque mélange. Les composés isolés, ceux modifés par hémisynthèse, ainsi que les mélanges de composition déterminée ont fait l’objet de tests d’activité anti-inflammatoire. Afin de modifier la structure de l’andrographolide sur des positions non accessibles par hémisynthèse, la synthèse totale et énantiosélective du produit naturel a été envisagée. Deux voies de synthèses ont été envisagées pour la préparation de ce composé : une voie biomimétique et une voie utilisant la cétone de Wieland-Miescher. Cette dernière voie est divisée en trois parties (cyclisation énantiosélective, fonctionnalisation du cycle A, fonctionnalisation du cycle B). Ainsi, nous avons pu mettre au point des méthodologies permettant de fonctionnaliser chaque cycle et d’accéder à la synthèse d’analogues de l’andrographolide.Andrographis paniculata is an Asian Echinacea. This plant is widely used in traditionnal remedies and folkloric medicines for thousands years and is reported to possess a wide spectrum of biological activities. A large number of diterpenoid ent-labdanes have been isolated from this plant, where the major compound is andrographolide, a diterpenoid lactone, that exhibits interesting anti-inflammatory activities on the NFB way. In order to understand and improve the anti-inflammatory activity of these compounds, we implemented a program aimed at their study. Qualitative analysis of crude extracts from dietary supplements allowed to obtain three major natural compounds, which were in a second time chemically modified. These products, as well as the crude extracts, where the composition was determined by a quantitative method, were used for the study of anti-inflammatory activity. Our aim was also to modify andrographolide on some positions not accessible by hemisynthesis. So total and enantioselective synthesis of andrographolide was investigated. Two ways were studied: biomimetic pathway, and modification of a bicyclic precursor that already possessed the ent-labdane configuration (Wieland-Miescher ketone). Methodology using Wieland-Miescher ketone was divided in three parts (enantioselective cyclisation, cycle A functionalisation, cycle B functionalisation). By this way, the bicyclic core was successfully functionnalised and analogues of andrographolide were prepared

Etude d'une famille de diterpènes d'origine naturelle ayant une activité anti-inflammatoire

Andrographis paniculata is an Asian Echinacea. This plant is widely used in traditionnal remedies and folkloric medicines for thousands years and is reported to possess a wide spectrum of biological activities. A large number of diterpenoid ent-labdanes have been isolated from this plant, where the major compound is andrographolide, a diterpenoid lactone, that exhibits interesting anti-inflammatory activities on the NFB way. In order to understand and improve the anti-inflammatory activity of these compounds, we implemented a program aimed at their study. Qualitative analysis of crude extracts from dietary supplements allowed to obtain three major natural compounds, which were in a second time chemically modified. These products, as well as the crude extracts, where the composition was determined by a quantitative method, were used for the study of anti-inflammatory activity. Our aim was also to modify andrographolide on some positions not accessible by hemisynthesis. So total and enantioselective synthesis of andrographolide was investigated. Two ways were studied: biomimetic pathway, and modification of a bicyclic precursor that already possessed the ent-labdane configuration (Wieland-Miescher ketone). Methodology using Wieland-Miescher ketone was divided in three parts (enantioselective cyclisation, cycle A functionalisation, cycle B functionalisation). By this way, the bicyclic core was successfully functionnalised and analogues of andrographolide were prepared.Andrographis paniculata est une échinacée d’origine asiatique utilisée depuis plus de deux milles ans en médecine traditionnelle asiatique. Ses activités anti-bactériennes, anti-virales et hépatoprotectrices, entre autre, en ont fait un sujet d’étude important depuis les trente dernières années. Cette plante est principalement constituée de diterpènes de série ent-labdanes, dont le composé majoritaire est l’andrographolide, une lactone diterpénique, qui a montré des propriétés anti-inflammatoires sur la voie NFB. C’est dans le but de comprendre et d’améliorer les activités anti-inflammatoires des composés issus de la plante que nous avons envisagé l’étude de la famille des andrographolides. Une étude qualitative d’extraits issus de compléments alimentaires a permis d’obtenir trois composés naturels, qui ont été pharmacomodulés chimiquement. De plus, une méthode quantitative de quatre extraits bruts a permis de déterminer la concentration des trois composés naturels isolés dans chaque mélange. Les composés isolés, ceux modifés par hémisynthèse, ainsi que les mélanges de composition déterminée ont fait l’objet de tests d’activité anti-inflammatoire. Afin de modifier la structure de l’andrographolide sur des positions non accessibles par hémisynthèse, la synthèse totale et énantiosélective du produit naturel a été envisagée. Deux voies de synthèses ont été envisagées pour la préparation de ce composé : une voie biomimétique et une voie utilisant la cétone de Wieland-Miescher. Cette dernière voie est divisée en trois parties (cyclisation énantiosélective, fonctionnalisation du cycle A, fonctionnalisation du cycle B). Ainsi, nous avons pu mettre au point des méthodologies permettant de fonctionnaliser chaque cycle et d’accéder à la synthèse d’analogues de l’andrographolide

Quantitative determination of Andrographolide and related compounds in Andrographis paniculata extracts and biological evaluation of their anti-inflammatory activity

Reprinted from: Foods 2019, 8, 683, doi:10.3390/foods81206International audienceExtraction, isolation and characterization of $Andrographis\ paniculata$ (A.p.) products were developed. Three natural diterpenes compounds were obtained and one was used for chemical modifications. Evaluation of their inhibition of TNF$\alpha$ induced NFκB transcriptional activity. A rapid analytical method for the determination and quantitation of three diterpenoid lactones (andrographolide 1, didehydroandrographolide 2, neoandrographiside 3) found in $A.\ paniculata$ extracts was investigated. After some optimizations on column type and injection solvent, the separation was achieved in 9 min on a monolithic Chromolith Performance RP18e column (100 mm × 4.6 mm ID, 2 µm), with a gradient solvent system of water and methanol, UV detection at 220 nm and ELSD detection. The method was proved to be suitable for the quantitation of these three diterpenes in four different commercial $Andrographis$ dietary supplements. The anti-inflammatory activities of a mixture of known composition have been evaluated showing differences in activity depending on the relative ratio of various diterpenes and also a possible synergic activity for some of them

Quantitative determination of Andrographolide and related compounds in Andrographis paniculata extracts and biological evaluation of their anti-inflammatory activity

International audienceExtraction, isolation and characterization of $Andrographis\ paniculata$ (A.p.) products were developed. Three natural diterpenes compounds were obtained and one was used for chemical modifications. Evaluation of their inhibition of TNF$\alpha$ induced NFκB transcriptional activity. A rapid analytical method for the determination and quantitation of three diterpenoid lactones (andrographolide 1, didehydroandrographolide 2, neoandrographiside 3) found in $A.\ paniculata$ extracts was investigated. After some optimizations on column type and injection solvent, the separation was achieved in 9 min on a monolithic Chromolith Performance RP18e column (100 mm × 4.6 mm ID, 2 µm), with a gradient solvent system of water and methanol, UV detection at 220 nm and ELSD detection. The method was proved to be suitable for the quantitation of these three diterpenes in four different commercial $Andrographis$ dietary supplements. The anti-inflammatory activities of a mixture of known composition have been evaluated showing differences in activity depending on the relative ratio of various diterpenes and also a possible synergic activity for some of them

Chemicals Inducing Seed Germination and Early Seedling Development

Seed germination and early seedling development are essential events in the plant life cycle that are controlled largely by the interplay and cross-talk between several plant hormones. Recently, major progress has been achieved in the elucidation at the molecular level of the signalling of these phytohormones. In this review, we summarise the data for the most promising classes of compounds, which could find potential agronomic applications for promoting seed germination and early seedling development even under abiotic stress conditions. Structural modifications of plant hormones are required to improve their biological performance and their specificity to allow commercial application