Laurence Dinan

Bio: Laurence Dinan is an academic researcher from University of Paris. The author has contributed to research in topics: Ecdysteroid & Metabolite. The author has an hindex of 2, co-authored 4 publications receiving 9 citations.

20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

Abstract: There is growing interest in the pharmaceutical and medical applications of 20-hydroxyecdysone (20E), a polyhydroxylated steroid which naturally occurs in low but very significant amounts in invertebrates, where it has hormonal roles, and in certain plant species, where it is believed to contribute to the deterrence of invertebrate predators. Studies in vivo and in vitro have revealed beneficial effects in mammals: anabolic, hypolipidemic, anti-diabetic, anti-inflammatory, hepatoprotective, etc. The possible mode of action in mammals has been determined recently, with the main mechanism involving the activation of the Mas1 receptor, a key component of the renin-angiotensin system, which would explain many of the pleiotropic effects observed in the different animal models. Processes have been developed to produce large amounts of pharmaceutical grade 20E, and regulatory preclinical studies have assessed its lack of toxicity. The effects of 20E have been evaluated in early stage clinical trials in healthy volunteers and in patients for the treatment of neuromuscular, cardio-metabolic or respiratory diseases. The prospects and limitations of developing 20E as a drug are discussed, including the requirement for a better evaluation of its safety and pharmacological profile and for developing a production process compliant with pharmaceutical standards.

Small‐scale analysis of phytoecdysteroids in seeds by HPLC‐DAD‐MS for the identification and quantification of specific analogues, dereplication and chemotaxonomy

Abstract: INTRODUCTION: Phytoecdysteroids are analogues of arthropod steroids occurring in plants. They contribute to invertebrate deterrence. A wide diversity of ecdysteroids occurs in phytoecdysteroid‐containing plant species, sometimes in high amounts. Ecdysteroids demonstrate potentially useful pharmaceutical actions in mammals. OBJECTIVES: Establish reversed‐phase high‐performance liquid chromatography with tandem mass spectrometry (RP‐HPLC‐MS/MS) and RP‐HPLC‐DAD‐MS (diode array detector mass spectrometry) methods for the separation, identification and quantification of ecdysteroids to screen for species containing significant amounts of 20‐hydroxyecdysone (20E) and other useful ecdysteroids. MATERIALS AND METHODS: Micro‐extracts of seed samples (ca. 30 mg) in 50% ethanol were subjected to RP‐SPE (solid‐phase extraction) purification prior to analysis by RP‐HPLC‐MS/MS and RP‐HPLC‐DAD‐MS. The method was initially applied to genera (Amaranthus, Centaurea, Lychnis, Ourisia, Serratula, Silene and Trollius) where high‐accumulating species had been previously encountered. Seeds of 160 randomly selected species, many of which have not previously been assessed, were then analysed. HPLC‐MS/MS with a short analysis time initially identifies ecdysteroid‐positive extracts and quantifies 20E. The positive extracts (20 ng 20E) are then analysed by HPLC‐MS/MS with a longer analysis time to identify and quantify 17 common phytoecdysteroids and, finally, HPLC‐DAD‐MS (0.1–0.25 μg 20E) is used to obtain UV‐ and MS‐spectra to confirm identifications or as a basis for characterisation of partially identified or novel analogues. RESULTS: Lychnis coronaria, Silene fimbriata and Silene hookeri ecdysteroids are characterised for the first time and those of Cucubalus baccifer and Ipheion uniflorum are more extensively characterised. CONCLUSIONS: The procedure provides a rapid/sensitive method for screening small plant samples for the presence, quantification and identification of ecdysteroids. It permits ready dereplication of samples, identifying extracts containing large amounts or novel analogues.

20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

Abstract: There is growing interest in the pharmaceutical and medical applications of 20-hydroxyecdysone (20E), a polyhydroxylated steroid which naturally occurs in low but very significant amounts in invertebrates, where it has hormonal roles, and in certain plant species, where it is believed to contribute to the deterrence of invertebrate predators. Studies in vivo and in vitro have revealed beneficial effects in mammals: anabolic, hypolipidemic, anti-diabetic, anti-inflammatory, hepatoprotective, etc. The possible mode of action in mammals has been determined recently, with the main mechanism involving the activation of the Mas1 receptor, a key component of the renin-angiotensin system, which would explain many of the pleiotropic effects observed in the different animal models. Processes have been developed to produce large amounts of pharmaceutical grade 20E, and regulatory preclinical studies have assessed its lack of toxicity. The effects of 20E have been evaluated in early stage clinical trials in healthy volunteers and in patients for the treatment of neuromuscular, cardio-metabolic or respiratory diseases. The prospects and limitations of developing 20E as a drug are discussed, including the requirement for a better evaluation of its safety and pharmacological profile and for developing a production process compliant with pharmaceutical standards.

Flavonoids of the Caryophyllaceae

Abstract: The plant family Caryophyllaceae, commonly known as the pink family, is divided into 3 subfamilies and contains over 80 genera with more than 2600 species that are widely distributed in temperate climate zones. Plants belonging to this family produce a variety of secondary metabolites important in an ecological context; however, some of these metabolites also show health-promoting activities. The most important classes of phytochemicals include saponins, phytoecdysteroids, other sterols, flavonoids, lignans, other polyphenols, essential oils, and N-containing compounds such as vitamins, alkaloids or cyclopeptides. Flavonoids are polyphenolic compounds that remain one of the most extensively studied constituents of the Caryophyllaceae family. Numerous structurally diverse aglycones, including flavones, flavonols, flavonones (dihydroflavones), flavonols, isoflavones, and their O- or C-glycosides, exhibit multiple interesting biological and pharmacological activities, such as antioxidant, anti-inflammatory, anti-oedemic, antimicrobial, and immunomodulatory effects. Thus, this review analysed the flavonoid composition of 26 different genera and more than 120 species of Caryophyllaceae for the first time.