Effects of Tryptophan Supplementation and Exercise on the Fate of Kynurenine Metabolites in Mice and Humans

The kynurenine pathway of tryptophan (TRP) degradation (KP) generates metabolites with effects on metabolism, immunity, and mental health. Endurance exercise training can change KP metabolites by changing the levels of KP enzymes in skeletal muscle. This leads to a metabolite pattern that favors energy expenditure and an anti-inflammatory immune cell profile and reduces neurotoxic metabolites. Here, we aimed to understand if TRP supplementation in untrained vs. trained subjects affects KP metabolite levels and biological effects. Our data show that chronic TRP supplementation in mice increases all KP metabolites in circulation, and that exercise reduces the neurotoxic branch of the pathway. However, in addition to increasing wheel running, we did not observe other effects of TRP supplementation on training adaptations, energy metabolism or behavior in mice. A similar increase in KP metabolites was seen in trained vs. untrained human volunteers that took a TRP drink while performing a bout of aerobic exercise. With this acute TRP administration, TRP and KYN were higher in the trained vs. the untrained group. Considering the many biological effects of the KP, which can lead to beneficial or deleterious effects to health, our data encourage future studies of the crosstalk between TRP supplementation and physical exercise.

Sesquiterpene Lactones with the 12,8-Guaianolide Skeleton from Algerian Centaurea omphalotricha

In continuing our investigation on the chemical diversity of Algerian plants, we examined Centaurea omphalotricha, whose chemical composition has been poorly studied. The present work was aimed at characterizing the secondary metabolite pattern of the CHCl3 extract of the aerial parts of this plant that displayed antiproliferative properties in a preliminary screening on HeLa cell line. The chemical analysis led us to characterize the bioactive oxygenated terpenoid fraction which includes, within major known metabolites, two new minor sesquiterpene lactones, centaurolide-A (1) and centaurolide-B (2). The structures of two compounds exhibiting the 12,8-guaianolide skeleton were determined by spectroscopic methods as well as by chemical correlation with inuviscolide (3), a well-known bioactive guaianolide isolated from Dittrichia (=Inula) viscosa. Centaurolides A and B represent the first report of 8,12-guaianolide skeleton in Centaurea genus. The effect of new compounds 1 and 2 and inuviscolide (3) on HeLa cell has also been evaluated.

Multi-Platform Metabolomics Analyses Revealed the Complexity of Serum Metabolites in LPS-Induced Neuroinflammed Rats Treated with Clinacanthus nutans Aqueous Extract

The use of metabolomics as a comprehensive tool in the analysis of metabolic profiles in disease progression and therapeutic intervention is rapidly advancing. Yet, a single analytical platform could not be applied to cover the entire spectrum of a biological sample’s metabolome. In the present paper, multi-platform metabolomics approaches were explored to determine the diverse rat sera metabolites extracted from intracerebroventricular lipopolysaccharides (LPS)-induced neuroinflammed rats treated with oral therapeutic interventions of positive drug (dextromethorphan, 5 mg/kg BW); with Clinacanthus nutans (CN) aqueous extract (CNE, 500 mg/kg BW); and with phosphate buffer saline (PBS) as the control group for 14 days. Analyzed by nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS) techniques, this study depicted the potential of metabolites associated with neuroinflammation and verified by MetDisease. The key observations in the perturbed metabolic pathways that showed ameliorative effects were linked to the class of amino acid and peptide metabolism involving valine, leucine, and isoleucine biosynthesis; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Lipid metabolism of arachidonic acid metabolism, glycerophospholipid metabolism, terpenoid backbone biosynthesis, and glycosphingolipid metabolism were also affected. Current findings suggested that the putative biomarkers, especially lysophosphatidic acid (LPA) and 5-diphosphomevalonic acid from glycerophospholipid and squalene/terpenoid and cholesterol biosynthesis, respectively, showed the ameliorative effects of the drug and CN treatments by controlling cell differentiation and proliferation. Our study proved that the complex and dynamic sera profiling affected during the CN treatment was greatly influenced by the analytical platform selection as integration between the two data yielded a more holistic summary of the metabolite pattern changes. Hence, an evidence-based herb, such as CN, can be used for novel diagnostic tools in the quest for ethnopharmacological studies.

Insight into the Metabolite Pattern of Psoriasis: Correlation among Homocysteine, Methionine, and Polyamines

Psoriasis is an incurable dermatological disorder, characterized by increased epidermal cell proliferation. Numerous studies have focused on the modulation of polyamine (PA) metabolism in psoriatic lesions, as well as the relationship between serum homocysteine (Hcy) levels and psoriasis severity. The correlation between Hcy and PA levels has not been investigated, although both of them depend on methionine (Met) loading. The aim of this study was to examine Met, Hcy, and polyamine levels in serum, saliva, lesions, and non-affected skin to investigate the eventual relationship between their levels in skin samples and to assess the correlation of each metabolite among the tested samples. This study was conducted on 24 patients with plaque-form psoriasis vulgaris. The original LC-MS/MS method was used for quantification of analytes. Hyperhomocysteinemia was observed and the serum levels of spermidine (Spd) and spermine (Spm) were also found to be elevated. A significant increase in Met (p < 0.05) and Spm (p < 0.001) concentrations in the psoriatic plaques were found, when compared to the non-affected skin. Significant correlations were established between all polyamines levels and between methionine and spermine in both types of cutaneous samples. This study illustrates the tight relationship between Met and Polyamine levels in epidermis of psoriatic patients. Our results could be helpful in psoriasis treatment, highlighting the importance of the balanced protein diet and intake of vitamins B12 and B9.

Metabolomics Analysis Reveals Tissue-Specific Metabolite Compositions in Leaf Blade and Traps of Carnivorous Nepenthes Plants

Nepenthes is a genus of carnivorous plants that evolved a pitfall trap, the pitcher, to catch and digest insect prey to obtain additional nutrients. Each pitcher is part of the whole leaf, together with a leaf blade. These two completely different parts of the same organ were studied separately in a non-targeted metabolomics approach in Nepenthes x ventrata, a robust natural hybrid. The first aim was the analysis and profiling of small (50–1000 m/z) polar and non-polar molecules to find a characteristic metabolite pattern for the particular tissues. Second, the impact of insect feeding on the metabolome of the pitcher and leaf blade was studied. Using UPLC-ESI-qTOF and cheminformatics, about 2000 features (MS/MS events) were detected in the two tissues. They showed a huge chemical diversity, harboring classes of chemical substances that significantly discriminate these tissues. Among the common constituents of N. x ventrata are phenolics, flavonoids and naphthoquinones, namely plumbagin, a characteristic compound for carnivorous Nepenthales, and many yet-unknown compounds. Upon insect feeding, only in pitchers in the polar compounds fraction, small but significant differences could be detected. By further integrating information with cheminformatics approaches, we provide and discuss evidence that the metabolite composition of the tissues can point to their function.