Kynurenines as a Novel Target for the Treatment of Inflammatory Disorders

Cells, Journal Year: 2024, Volume and Issue: 13(15), P. 1259 - 1259

Published: July 26, 2024

This review discusses the potential of targeting kynurenine pathway (KP) in treatment inflammatory diseases. The KP, responsible for catabolism amino acid tryptophan (TRP), produces metabolites that regulate various physiological processes, including inflammation, cell cycle, and neurotransmission. These metabolites, although necessary to maintain immune balance, may accumulate excessively during leading systemic disorders. Key KP enzymes such as indoleamine 2,3-dioxygenase 1 (IDO1), 2 (IDO2), (TDO), 3-monooxygenase (KMO) have been considered promising therapeutic targets. It was highlighted both inhibition activation these be beneficial, depending on specific disorder. Several conditions, autoimmune diseases, which modulation activity holds promise, described detail. Preclinical studies suggest this an effective strategy diseases options are currently limited. Taken together, highlights importance further research clinical application enzyme development new strategies

Language: Английский

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Depression, stress, and tryptophan metabolism through the kynurenine pathway: treatment strategies from the perspective of Chinese herbal medicine

Metabolic Brain Disease, Journal Year: 2024, Volume and Issue: 40(1)

Published: Nov. 15, 2024

Language: Английский

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A Novel RP-UHPLC-MS/MS Approach for the Determination of Tryptophan Metabolites Derivatized with 2-Bromo-4′-Nitroacetophenone

Biomedicines, Journal Year: 2024, Volume and Issue: 12(5), P. 1003 - 1003

Published: May 2, 2024

Many biologically active metabolites of the essential amino acid L-tryptophan (Trp) are associated with different neurodegenerative diseases and neurological disorders. Precise reliable methods for their determination needed. Variability in physicochemical properties makes analytical process challenging. In this case, chemical modification analyte derivatization could come into play. Here, we introduce a novel fast reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) coupled tandem mass spectrometry (MS/MS) method Trp its ten human plasma samples after 2-bromo-4′-nitroacetophenone (BNAP). The procedure was optimized terms incubation time, temperature, concentration, volume reagent. Method development comprises choice suitable stationary phase, mobile phase composition, gradient elution optimization. developed validated according to ICH guidelines. Results all validation parameters were within acceptance criteria guideline, i.e., intra- inter-day precision (expressed as relative standard deviation; RSD) range 0.5–8.2% 2.3–7.4%, accuracy 93.3–109.7% 94.7–110.1%, limits detection (LODs) 0.15–9.43 ng/mL, coefficients (R2) higher than 0.9906, carryovers were, cases, less 8.8%. practicability evaluated using blue applicability grade index (BAGI) score 65. Finally, used analysis Alzheimer’s disease healthy control prove applicability. Statistical revealed significant changes picolinic (PA), anthranilic (AA), 5 hydroxyindole-3-acetic (5-OH IAA), quinolinic (QA) concentration levels. This serve basis future studies that will be conducted large cohort patients.

Language: Английский

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The Comparative Effects Between Long‐Term and Short‐Term Treatment of Finasteride on Anxiety‐Like and Depression‐Like Behaviors in Early Senescent Male Rats

Journal of Neuroscience Research, Journal Year: 2024, Volume and Issue: 102(10)

Published: Oct. 1, 2024

ABSTRACT This study aims to compare the efficacy of 5‐alpha‐reductase inhibitors (5ARIs) on anxiety and depression between long‐term short‐term treatment followed by withdrawal in d ‐galactose (Dgal)–induced senescent male rats. Thirty‐two, 8‐week‐old, Wistar rats were divided into two groups: control Dgal‐treated (150 mg/kg/day; subcutaneously) for 18 weeks. At week 13, subdivided three subgroups: (1) vehicle (DgV), (2) with 5ARIs, Finasteride 5 mg/kg/day, per oral 6 weeks (DgF), (3) 2 a 4‐week period (DgW). Anxiety assessed using elevated‐plus maze (EPM) splash test (ST). Blood was collected biochemical analysis. After euthanasia, brains removed examine brain inflammation, oxidative stress, neuroactive steroids, metabolites, markers. We found that DgV exhibited metabolic disturbance reduced preference index EPM, grooming duration ST. Increased neurotoxic along increased inflammation/oxidative microglia complexity observed Both therapeutic approaches improved parameters open arm EPM rats, while only DgF Our results indicate Fin reduces depression‐like anxiety‐like behaviors reducing senescent. In conclusion, 5ARIs is more effective alleviating than Dgal‐induced early

Language: Английский

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Exploring tryptophan metabolism in cardiometabolic diseases

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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