Modulation of chicken gut contractility by Melissa officinalis-ex vivo study.

Melissa officinalis (lemon balm) has a long history of being used in traditional medicine for the treatment of gastrointestinal tract disorders in human thanks to its spasmolytic and stress reducing effects. These pharmacological properties have been confirmed in laboratory animals. Unfortunately, in the case of veterinary medicine, the effect of lemon balm on gut contractility has been never subjected to a detailed investigation. On the other hand, there is urgent need of new drugs that could be safely used in animals for both, causative and symptomatic treatment. In broiler chicken, one of the major health concerns includes gastrointestinal disorders with gut hypermotility. Thus, it is crucial to verify the potential utility of Melissa officinalis extract in gastrointestinal dysmotilities. The aim of the study was to analyze the effect of lemon balm extract and some of its active ingredients on chicken intestine motility. The study was performed on isolated proximal and distal jejunum preparations collected from broiler chicken which underwent routine slaughter procedure. The effect of lemon balm and 3 phenolic acids (rosmarinic, chlorogenic, and lithospermic) was verified under isometric conditions, toward spontaneous and acetylcholine (ACh)-induced smooth muscle activity. Surprisingly, M. officinalis turned out to be rather a myocontractile agent as it increased ACh-provoked contractility of proximal and distal jejunum strips and also intensified the spontaneous activity of distal jejunum. Only in the case of proximal intestine lemon balm extract diminished the force of spontaneous motoric activity up to approx. Sixty-seven percent of the control conditions. None of the tested phenolic acids displayed analog effect with the whole plant extract. In fact in the case of ACh-induced contractility, the acids had the opposite, that is, myorelaxant, effect than the extract, with a small exception of lithospermic acid in distal jejunum. Thus, it is impossible to assign one or more individual constituents to the effect of the whole Melissa officinalis extract. The obtained results do not support the use of lemon balm extract in broiler diseases which are accompanied by gut motility disturbances, including diarrhea.

MixONat, a Software for the Dereplication of Mixtures Based on 13C NMR Spectroscopy.

Whether chemists or biologists, researchers dealing with metabolomics require tools to decipher complex mixtures. As a part of metabolomics and initially dedicated to identifying bioactive natural products, dereplication aims at reducing the usual time-consuming process of known compounds isolation. Mass spectrometry and nuclear magnetic resonance are the most commonly reported analytical tools during dereplication analysis. Though it has low sensitivity, 13C NMR has many advantages for such a study. Notably, it is nonspecific allowing simultaneous high-resolution analysis of any organic compounds including stereoisomers. Since NMR spectrometers nowadays provide useful data sets in a reasonable time frame, we have embarked upon writing software dedicated to 13C NMR dereplication. The present study describes the development of a freely distributed algorithm, namely MixONat and its ability to help researchers decipher complex mixtures. Based on Python 3.5, MixONat analyses a {1H}-13C NMR spectrum optionally combined with DEPT-135 and 90 data-to distinguish carbon types (i.e., CH3, CH2, CH, and C)-as well as a MW filtering. The software requires predicted or experimental carbon chemical shifts (δc) databases and displays results that can be refined based on user interactions. As a proof of concept, this 13C NMR dereplication strategy was evaluated on mixtures of increasing complexity and exhibiting pharmaceutical (poppy alkaloids), nutritional (rosemary extracts) or cosmetics (mangosteen peel extract) applications. Associated results were compared with other methods commonly used for dereplication. MixONat gave coherent results that rapidly oriented the user toward the correct structural types of secondary metabolites, allowing the user to distinguish between structurally close natural products, including stereoisomers.

Semisynthetic and Natural Garcinoic Acid Isoforms as New mPGES-1 Inhibitors.

Over the last twenty years, tocotrienol analogues raised great interest because of their higher level and larger domain of biological activities when compared with tocopherols. Amongst the most promising therapeutic application, anti-inflammatory potency has been evaluated through the inhibition of various mediators of inflammation. Here, we worked on the isolation of two natural isoforms of garcinoic acid (i.e., δ and γ) from two different sources, respectively, Garcinia kola seeds and Garcinia amplexicaulis bark. We also developed semisynthetic strategies to access the other two non-natural α- and ß-garcinoic acid isoforms. In the next stage of our work, microsomal prostaglandin E2 synthase was defined as a target to evaluate the anti-inflammatory potential of the four garcinoic acid isomers. Both dimethylated isoforms, ß- and γ-garcinoic acid, exhibited the lowest IC50, 2.8 µM and 2.0 µM, respectively. These results showed that the affinity of tocotrienol analogues to microsomal prostaglandin E2 synthase-1 most probably contributes to the anti-inflammatory potential of this class of derivatives.