Neuroprotective Natural Products’ Regulatory Effects on Depression via Gut–Brain Axis Targeting Tryptophan

Abstract

L-tryptophan (Trp) contributes to regulating bilateral communication of the gut­–brain axis. It undergoes three major metabolic pathways, which lead to formation of kynurenine, serotonin (5-HT), and indole derivatives (under the control of the microbiota). Metabolites from the principal Trp pathway, kynurenic acid and quinolinic acid, exhibit neuroprotective activity, while picolinic acid exhibits antioxidant activity, and 5-HT modulates appetite, sleep cycle, and pain. Abnormality in Trp plays crucial roles in diseases, including depression, colitis, ulcer, and gut microbiota-related dysfunctions. To address these diseases, the use of natural products could be a favorable alternative because they are a rich source of compounds that can modulate the activity of Trp and combat various diseases through modulating different signaling pathways, including the gut microbiota, kynurenine pathway, and serotonin pathway. Alterations in the signaling cascade pathways via different phytochemicals may help us explore the deep relationships of the gut–brain axis to study neuroprotection. This review highlights the roles of natural products and their metabolites targeting Trp in different diseases. Additionally, the role of Trp metabolites in the regulation of neuroprotective and gastroprotective activities is discussed. This study compiles the literature on novel, potent neuroprotective agents and their action mechanisms in the gut–brain axis and proposes prospective future studies to identify more pharmaceuticals based on signaling pathways targeting Trp.

Antidepressive Effect of Natural Products and Their Derivatives Targeting BDNF-TrkB in Gut–Brain Axis

“…Numerous studies have focused on the intake of flavonoids through vegetables and fruits to reduce the risk of depression [ 105 , 106 ]. A randomized controlled study was conducted among young Korean adults in treatment and placebo groups.…”

“…It improves post-traumatic stress disorder (PTSD)-like behavior in mice by rebalancing neuroinflammatory and oxidative stress in the brain. The restoration of BDNF expression may be a potential mechanism underlying the anti-PTSD effects of lycopene [ 105 , 152 ]. Lycopene has been shown to improve dextran sulfate sodium induced colitis depression and behavioral disorders via balancing the microbiota–gut–brain axis balance by upregulating BDNF expression and postsynaptic density protein.…”

Measuring tryptophan dynamics using fast scan cyclic voltammetry at carbon fiber microelectrodes with improved sensitivity and selectivity

“…kynurenine, vitamin B 6 ). 12,13 As a result, it has been hypothesized that Trp itself plays crucial roles in the brain, the gut, and the various disorders that involve the gut-brain axis, including depression [14][15][16][17][18][19][20] and autism spectrum disorder. [21][22][23][24][25] Humans obtain most of necessary Trp from diet, but Candida, Streptococcus, Escherichia, Enterococus, and other microorganisms in the gut microbiome express Trp synthase that catalyzes the Trp biosynthesis from serine and indole-3glycerol-phosphate.…”

A meta-analysis of the effect of multidisciplinary comprehensive care on health-related quality of life and Unified Parkinson’s Disease Rating Scale in Parkinson’s disease

“…3,4 Parkinson's disease is characterized by irregularities of movement, including tremors, gait and balance issues, and slowness of movement. 5 The abnormalities of neuronal and muscular activity that are associated with these symptoms are well understood. 6 Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb's position and speed, are controlled and coordinated.…”