Lycopene alleviates BCG-induced depressive phenotypes in mice by disrupting 5-HT3 receptor - IDO1 interplay in the brain.

The 5-HT3 receptor and indoleamine 2,3-dioxygenase 1 (IDO1) enzyme play a crucial role in the pathogenesis of depression as their activation reduces serotonin contents in the brain. Since molecular docking analysis revealed lycopene as a potent 5-HT3 receptor antagonist and IDO1 inhibitor, we hypothesized that lycopene might disrupt the interplay between the 5-HT3 receptor and IDO1 to mitigate depression. In mice, the depression-like phenotypes were induced by inoculating Bacillus Calmette-Guerin (BCG). Lycopene (intraperitoneal; i.p.) was administered alone or in combination with 5-HT3 receptor antagonist ondansetron (i.p.) or IDO1 inhibitor minocycline (i.p.), and the behavioral screening was performed by the sucrose preference test, open field test, tail suspension test, and splash test which are based on the different principles. Further, the brains were subjected to the biochemical analysis of serotonin and its precursor tryptophan by the HPLC. The results showed depression-like behavior in BCG-inoculated mice, which was reversed by lycopene administration. Moreover, prior treatment with ondansetron or minocycline potentiated the antidepressant action of lycopene. Minocycline pretreatment also enhanced the antidepressant effect of ondansetron indicating the regulation of IDO1 activity by 5-HT3 receptor-triggered signaling. Biochemical analysis of brain samples revealed a drastic reduction in the levels of tryptophan and serotonin in depressed animals, which were restored following treatment with lycopene and its combination with ondansetron or minocycline. Taken together, the data from molecular docking, behavioral experiments, and biochemical estimation suggest that lycopene might block the 5-HT3 receptor and consequently inhibit the activity of IDO1 to ameliorate BCG-induced depression in mice.

Quinquennial Review of Progress in Degradation Studies and Impurity Profiling: An Instrumental Perspective Statistics.

Degradation studies of drug give insightful information about the intrinsic stability of the molecule, the possible degradents formed during shelf life and thus, aid in the subsequent development of its stable formulation. For identification and characterization of degradents and impurities formed during stress studies, various analytical techniques are required including hyphenated techniques. Chromatographic methods play a crucial role in the field of degradation and impurity profiling. Many of these methods have been introduced for the qualitative and quantitative analysis of drugs and their formulations. This article encompasses current trends in analytical methods used for degradents, foreign matter, genotoxic impurity, and impurity profiling studies of the last five years (2013-2017). It further provides an insight into the development of various analytical methods such as hyphenated and non-hyphenated techniques those used in the analysis of pharmaceuticals. Various components used in chromatographic development such as mobile phase, buffer solutions, elution modes, columns, column temperature, and detectors are emphasized. Techniques developed by systematic Analytical Quality by Design (AQbD) approach are also discussed. Additionally, the in silico toxicity prediction studies and the methods developed for genotoxic impurity analysis are briefly explained.