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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.

Wheat germ (WG) is a by-product of wheat milling and comprises many bioactive compounds. This study aimed to compare the antioxidant and antilipidemic effects of different WG extracts (WGEs) by analyzing candidate bioactive compounds such as carotenoids, tocopherols, γ-oryzanol, and biogenic amines by reversed-phase high-performance liquid chromatography. Antioxidant activity was determined using the ABTS, DPPH, and FRAP assays. The antilipidemic effect was evaluated in palmitic acid-induced steatosis in HepG2 hepatocytes and 3T3-L1 adipocytes. Cellular lipid accumulation was assessed by Oil Red O staining and a cellular triglyceride content assay. All analyzed WGEs showed significant antioxidant potential, although some bioactive compounds, such as carotenoids, tocopherols, and γ-oryzanol, were the highest in the ethanol extract. Correlation analysis revealed the antioxidant potential of all identified biogenic amines except for spermidine. Ethanol and n-hexane extracts significantly inhibited cellular lipid accumulation in cell models. These results suggest that WGEs exhibit promising antioxidant potential, with a variety of bioactive compounds. Collectively, the findings of this study suggest that bioactive compounds in WGEs attenuate plasma lipid and oxidation levels. In conclusion, WG can be used as a natural antioxidant and nutraceutical using appropriate solvents and extraction methods.

This systematic review and meta-analysis aim to evaluate the association of wheat germ interventions and metabolic markers. An electronic search was performed by mid-May 2019 in the PubMed, Google Scholar, and Web of Science databases. Quality was evaluated using the risk of bias assessment tools. Thirty-three randomized controlled trials (RCTs) were identified, among which ten were suitable and systematically reviewed based on biomarkers (cholesterol, triglycerides, glucose, and oxidative stress). Three biomarkers in five eligible studies were investigated by meta-analysis. Total cholesterol showed non-significant results (p = 0.98), with standard mean difference (SMD) of-0.01 (95% confidence interval;-0.17, 0.16). The SMD was-0.06 (95% CI-0.41, 0.29, n = 4) for triglycerides and-0.09 (95% CI-0.62, 0.45, n = 2) for glucose. No biomarkers showed heterogeneity (0%). This review revealed non-significant association between wheat germ interventions and metabolic markers. Sensitive analysis with high-quality RCTs may be worth trying.

Modern neurological approaches enable detailed studies on the pathophysiology and treatment of depression. An imbalance in the microbiota–gut–brain axis contributes to the pathogenesis of depression. This extensive review aimed to elucidate the antidepressive effects of brain-derived neurotrophic factor (BDNF)-targeting therapeutic natural products and their derivatives on the gut–brain axis. This information could facilitate the development of novel antidepressant drugs. BDNF is crucial for neuronal genesis, growth, differentiation, survival, plasticity, and synaptic transmission. Signaling via BDNF and its receptor tropomyosin receptor kinase B (TrkB) plays a vital role in the etiopathogenesis of depression and the therapeutic mechanism of antidepressants. This comprehensive review provides information to researchers and scientists for the identification of novel therapeutic approaches for neuropsychiatric disorders, especially depression and stress. Future research should aim to determine the possible causative role of BDNF-TrkB in the gut–brain axis in depression, which will require further animal and clinical research as well as the development of analytical approaches.