Patrick Poucheret

Characterization, anti-oxidative and anti-inflammatory effects of Costa Rican noni juice (Morinda citrifolia L.)

AIM OF THE STUDY Noni fruit (Morinda citrifolia L.) juice has been used for more than 2000 years in Polynesia as a traditional folk medicine. The aim of the present study was to finely characterize noni juice from Costa Rica and to evaluate its anti-oxidative and anti-inflammatory activities. MATERIALS AND METHODS A microfiltrated noni juice was prepared with Costarican nonis. HPLC-DAD and Electro Spray Ionization Mass Spectrometric detection (HPLC-ESI-MS) were used to identify phenolic compounds and iridoids. The anti-oxidative activity of noni juice was measured in vitro by both Oxygen Radical Absorbance Capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging methods. The anti-inflammatory effects of noni juice were investigated in vitro by: measuring its effect on nitric oxide and prostaglandin E2 production by activated macrophages, evaluating its inhibitory activities on cyclooxygenase (COX)-1 and -2 and in vivo on a carrageenan-induced paw oedema model in rats. RESULTS Several polyphenols belonging to the coumarin, flavonoid and phenolic acid groups, and two iridoids were identified. Noni juice demonstrated a mean range free radical scavenging capacity. Furthermore, it also reduced carrageenan-induced paw oedema, directly inhibited cyclooxygenase COX-1 and COX-2 activities and inhibited the production of nitric oxide (NO) and prostaglandins E(2) (PGE(2)) in activated J774 cells, in a dose dependent manner. CONCLUSIONS This study showed that nonis biological effects include: (1) anti-oxidant properties probably associated with phenolic compounds, iridoids and ascorbic acid and (2) anti-inflammatory action through NO and PGE(2) pathways that might also be strengthened by anti-oxidant effects.

NP03, a novel low-dose lithium formulation, is neuroprotective in the YAC128 mouse model of Huntington disease.

Huntington disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene, remains without a treatment to modify the course of the illness. Lithium, a drug widely used for the treatment of bipolar disorder, has been shown to exert neuroprotective effects in a number of models of neurological disease but may have various toxic effects at conventional therapeutic doses. We examined whether NP03, a novel low-dose lithium microemulsion, would improve the disease phenotypes in the YAC128 mouse model of HD. We demonstrate that NP03 improves motor function, ameliorates the neuropathological deficits in striatal volume, neuronal counts, and DARPP-32 expression, and partially rescues testicular atrophy in YAC128 mice. These positive effects were accompanied by improvements in multiple biochemical endpoints associated with the pathogenesis of HD, including normalization of caspase-6 activation and amelioration of deficits in BDNF levels, and with no lithium-related toxicity. Our findings demonstrate that NP03 ameliorates the motor and neuropathological phenotypes in the YAC128 mouse model of HD, and represents a potential therapeutic approach for HD.

Amatoxin poisoning treatment decision-making: pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis.

Ninety percent of fatal higher fungus poisoning is due to amatoxin-containing mushroom species. In addition to absence of antidote, no chemotherapeutic consensus was reported. The aim of the present study is to perform a retrospective multidimensional multivariate statistic analysis of 2110 amatoxin poisoning clinical cases, in order to optimize therapeutic decision-making. Our results allowed to classify drugs as a function of their influence on one major parameter: patient survival. Active principles were classified as first intention, second intention, adjuvant or controversial pharmaco-therapeutic clinical intervention. We conclude that (1) retrospective multidimensional multivariate statistic analysis of complex clinical dataset might help future therapeutic decision-making and (2) drugs such as silybin, N-acetylcystein and putatively ceftazidime are clearly associated, in amatoxin poisoning context, with higher level of patient survival.

Awara (Astrocaryum vulgare M.) pulp oil: chemical characterization, and anti-inflammatory properties in a mice model of endotoxic shock and a rat model of pulmonary inflammation.

Awara (Astrocaryum vulgare M.) is a palm fruit mainly used in nutrition. We analysed the pulp oil for fatty acid, tocopherol, carotenoid, and phytosterol and we evaluated whether this oil may attenuate inflammation in vivo. In an endotoxic shock model, awara pulp oil treatment decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines. In a pulmonary inflammation model, awara pulp oil treatment reduced eosinophil and lymphocyte numbers recovered into the broncho-alveolar lavages. These results suggest that awara pulp oil administration can efficiently counteract an acute and chronic inflammatory response in vivo that is probably mediated by fatty acids and minor compounds.

Effect of physiological harvest stages on the composition of bioactive compounds in Cavendish bananas

The combined influence of maturation, ripening, and climate on the profile of bioactive compounds was studied in banana (Musa acuminata, AAA, Cavendish, cv. Grande Naine). Their bioactive compounds were determined by the Folin-Ciocalteu assay and high-performance thin layer chromatographic (HPTLC) method. The polyphenol content of bananas harvested after 400 degree days remained unchanged during ripening, while bananas harvested after 600 and 900 degree days exhibited a significant polyphenol increase. Although dopamine was the polyphenol with the highest concentration in banana peels during the green developmental stage and ripening, its kinetics differed from the total polyphenol profile. Our results showed that this matrix of choice (maturation, ripening, and climate) may allow selection of the banana (M. acuminata, AAA, Cavendish, cv. Grande Naine) status that will produce optimal concentrations of identified compounds with human health relevance.

Fruits and vegetables, as a source of nutritional compounds and phytochemicals: Changes in bioactive compounds during lactic fermentation

Nutritional recommendations emphasize fruit and vegetable consumption. This is related to health-benefits associated with bioactive nutritive molecules (nutrients, vitamins, minerals, fibers, …) as well as non-nutritive phytochemicals (phenolic compounds, flavonoids, bioactive peptides, …) content of these types of foods. Fermented fruit or vegetable products are part of various diets worldwide. Lactic acid bacteria (LAB) fermentation is common among the various fermentation processes used. It produces changes in both profile and types of bioactive compounds. Molecules such as bioactive peptides, short chain fatty acids or polysaccharides are generated while sugar content or anti-nutritional compounds are decreased and phenolic compounds are converted to molecules with added biological value. These transformations, associated with prebiotic and/or probiotic potential supply as well as improvement of food components bioaccessibility and bioavailability, result in modifications of health-related properties. Lastly, interactions between ingested fermented food, intestinal microbiota and their correlations to metabolomics profiles and health represent an important perspective deserving to be further explored.

Evaluation of antioxidant and antiproliferative activities of dyeing plants

Abstract Natural dyes are nowadays re—investigated but few data are available about their biological properties. In this study, ten dyeing plants from several genera (belonging to Anacardiaceae, Asteraceae, Betulaceae, Resedaceae, Rosaceae, Rubiaceae) were investigated for both antioxidant and antiproliferative activities. Aqueous crude extracts containing flavonoids associated with either phenolic acids or tannins were particularly antioxidant whereas no extract seemed to present antiproliferative properties suggesting a potential absence of toxicity. Primary pharmacological data from this study are discussed in relation with dyeing properties of plant species in order to highlight the uses of multi—functionalised natural products.

Pulmonary anti-inflammatory effects and spasmolytic properties of Costa Rican noni juice (Morinda citrifolia L.).

ETHNOPHARMACOLOGICAL RELEVANCE Morinda citrifolia L. (Noni) is a medicinal plant used in Polynesia for many properties such as anti-inflammatory, anti-diabetic and antineoplastic effects. Recent studies showed that noni juice have anti-oxidant and acute anti-inflammatory activities likely due to polyphenols, iridoids and vitamin C content. The present study was undertaken to evaluate chronic anti-inflammatory and spasmolytic effects of noni juice. MATERIALS AND METHODS Therefore, we evaluated the effect of oral or intraperitoneal administrations of noni juice in vivo on the lung inflammation in ovalbumin (OVA) sensitized Brown Norway rat (with prednisolone 10mg/kg intraperitoneously as reference compound) and the ex vivo effect of noni juice on BaCl2 (calcium signal) or methacholine (cholinergic signal) induced spasms in jejunum segments. RESULTS We found that noni juice (intraperitoneously 2.17mL/kg and orally 4.55mL/kg) reduced the inflammation in OVA-sensitized Brown Norway rat with regard to the decreased number of inflammatory cells in lung (macrophages minus 20-26%, lymphocytes minus 58-34%, eosinophils minus 53-30%, neutrophils minus 70-28% respectively). Noni juice demonstrated a dose-dependent NO scavenging effect up to 8.1nmol of nitrites for 50µL of noni juice. In addition noni juice inhibited (up to 90%) calcium and cholinergic induced spasms on the jejunum segments model with a rightward shift of the concentration response curve. CONCLUSION We describe for the first time that noni juice demonstrate (1) a chronic anti-inflammatory activity on sensitized lungs along with (2) a spasmolytic effect integrating a calcium channel blocker activity component.

Influence of geography, seasons and pedology on chemical composition and anti-inflammatory activities of essential oils from Lippia multiflora Mold leaves.

ETHNOPHARMACOLOGICAL RELEVANCE Lippia multiflora is a plant with nutritional and pharmaco-therapeutic properties that is native to central and occidental Africa. The potential effects of plants on health are associated with their chemical composition. Therefore, the present study aimed to identify chemical variations in essential oils of Lippia multiflora as a function of geographic origin and time of annual harvest to determine optimal chemical profiles for ethno-pharmacotherapeutic applications. MATERIALS AND METHODS Experimental plants were cultivated at Abidjan (LPA), Toumodi (LPT) and Bondoukou (LPB). Natural Lippia multiflora seeds were sourced to produce standardized plants over a period of six months. Standard plants (n=40) were re-introduced into natural plots, cultivated for 12 months and leaves were sampled monthly in a standardized fashion. Essentials oils (n=36) were then extracted from these samples by hydro-distillation according to the European Pharmacopoeia and qualitatively and quantitatively analyzed using GC/FID and GC/MS. These data were then analyzed using Principal Component Analysis (PCA). Anti-inflammatory properties were also assessed against activated macrophages in vitro. RESULTS The results indicated that chemical profiles and essential oil yields vary according to the location where the plants were cultivated. One essential oil chemotype corresponded to the LPA and LPT sites and one corresponded to the LPB site. Statistical analysis of the chemical profiles and monthly evolution of the three sites over a period of one year allowed assessment of variations in composition and the subsequent choice of the optimal harvest time for ethnopharmacological applications. Anti-inflammatory activity apparently correlated with chemical profiles of essential oils and the geographic origins of the plants. CONCLUSION The optimal harvest time was associated with the maximum yield of pharmacological compounds with the most potential interest for health.

Decision-Making for the Detection of Amatoxin Poisoning: A Comparative Study of Standard Analytical Methods

Abstract Amatoxin-containing mushroom poisonings are recorded worldwide and the frequency increases due to confusion with other macrofungi. Affected regions are characterized by important disparities in relation to available technological equipment for analytical identification of amatoxins. In this context the present study was designed to define advantages and disadvantages of the most accessible standard analytical methods for amatoxin detection. Several methods were compared: (1) a commercialized immunoassay kit, (2) standard high-performance liquid chromatography (HPLC) and (3) high-performance thin layer chromatography (HP-TLC). For each method, linearity, limit of detection (LOD), limit of quantification (LOQ) and recovery were determined. Six macrofungi were analysed using these compared methods, three known to contain amatoxins: Amanita phalloides, Amanita virosa, Lepiota josserandii, and three free-amatoxin containing macrofungi: Amanita muscaria, Macrolepiota procera and Omphalotus olearius. Our results will allow for a choice of method with full knowledge of advantages and disadvantages of each technique as a function of local technological possibilities when facing suspected poisoning due to amatoxin-containing mushrooms. The final aim is to be able to reach faster and effective diagnosis in order to save a patients life.