Tryptophan Metabolism and Related Pathways in Psychoneuroimmunology: The Impact of Nutrition and Lifestyle.

In the past, accelerated tryptophan breakdown was considered to be a feature of clinical conditions, such as infection, inflammation, and malignant disease. More recently, however, the focus has changed to include the additional modulation of tryptophan metabolism by changes in nutrition and microbiota composition. The regulation of tryptophan concentration is critical for the maintenance of systemic homeostasis because it integrates essential pathways involved in nutrient sensing, metabolic stress response, and immunity. In addition to tryptophan being important as a precursor for the synthesis of the neurotransmitter serotonin, several catabolites along the kynurenine axis are neuroactive. This emphasizes the importance of the immunometabolic fate of this amino acid for processes relevant to neuropsychiatric symptoms. In humans, besides hepatic catabolism, there is usually a strong relationship between immune activation-associated tryptophan breakdown and increased levels of biomarkers, such as neopterin, which has particular relevance for both acute and chronic diseases. A shift towards neopterin synthesis during oxidative stress may indicate a corresponding decrease in tetrahydrobiopterin, a cofactor of several mono-oxygenases, providing a further link between tryptophan metabolism and serotonergic and catecholaminergic neurotransmission. The psychoneuroimmunological consequences of tryptophan metabolism and the susceptibility of this pathway to modulation by a variety of nutritional and lifestyle-related factors have important implications for the development of both diagnostic and treatment options.

Terpenoids from the Stems of Fissistigma polyanthoides and Their Anti-Inflammatory Activity.

Twelve new terpenoids (1-12) were isolated from the stems of Fissistigma polyanthoides, an anti-inflammatory medicinal plant traditionally used in Vietnam. Most of them (1-9) possess a sesquiterpenoid backbone (e.g., guaiane, germacrane, and cadinane) connected to a 2'-O-trans-cinnamoyl)-ß-d-glucopyranose moiety, which is rare in Nature. Among them, compounds 4 (5/8-fused ring) and 6 (spiran [4,5] ring) represent uncommonly rearranged sesquiterpenoids. Compounds 10-12 are a novel monoterpene and two megastigmane derivatives, respectively. The individual structures were elucidated by combining NMR and MS data, and their configuration was established in NOESY and ECD experiments. Compounds 1-9 were also examined for their potential to interact with nuclear factor-kappa B activator protein 1 (NF-κB/AP-1) signaling by using the myelomonocytic reporter cell line THP-1Blue-CD14. Compounds 1-5 showed dose-dependent inhibitory effects [IC50 13.7 µM (1) to 49.0 µM (5)] on lipopolysaccharide-stimulated cells. However, compounds 1 to 4 also negatively affected cell viability in the same concentration range, while compound 5 was less potently cytotoxic.