Redox balance is essential to maintain the body’s normal metabolism. Once disrupted, it may lead to various chronic diseases, such as diabetes, neurodegenerative diseases, cardiovascular diseases, inflammatory diseases, cancer, aging, etc. Oxidative stress can cause or aggravate a series of pathological processes. Inhibition of oxidative stress and related pathological processes can help to ameliorate these chronic diseases, which have been found to be associated with Nrf2 activation. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damage, but also directly regulate genes related to the above-mentioned pathological processes to counter the corresponding changes. Therefore, targeting Nrf2 has great potential for the prevention or treatment of chronic diseases, and many natural phytochemicals have been reported as Nrf2 activators although the defined mechanisms remain to be elucidated. This review article focuses on the possible mechanism of Nrf2 activation by natural phytochemicals in the prevention or treatment of chronic diseases and the regulation of oxidative stress. Moreover, the current clinical trials of phytochemical-originated drug discovery by targeting the Nrf2-ARE pathway were also summarized; the outcomes or the relationship between phytochemicals and chronic diseases prevention are finally analyzed to propose the future research strategies and prospective.

Background: Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH. Method: To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH. Results: Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer. Conclusion: The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.

As a group of naturally occurring peptides in various foods, γ-glutamyl peptides possess a unique Kokumi taste and health benefits. However, few studies have focused on the functionality of γ-glutamyl peptides. In this study, the γ-[glutamyl] _{(n=1, 2, 3)}-tryptophan peptides were synthesized from a solution of glutamine (Gln) and tryptophan (Trp) employing L-glutaminase from Bacillus amyloliquefaciens. Four different γ-glutamyl peptides were identified from the reaction mixture by UPLC-Q-TOF-MS/MS. Under optimal conditions of pH 10, 37 °C, 3 h, 0.1 mol/L Gln: 0.1 mol/L Trp = 1:3, and glutaminase at 0.1% (m/v), the yields of γ-l-glutamyl-l-tryptophan (γ-EW), γ-l-glutamyl-γ-l-glutamyl-l-tryptophan (γ-EEW) and γ-l-glutamyl-γ-l-glutamyl-γ-l-glutamyl-l-tryptophan (γ-EEEW) were 51.02%, 26.12% and 1.91% respectively. The antioxidant properties of the reaction mixture and the two peptides (γ-EW, γ-EEW) identified from the reaction media were further compared. Results showed that γ-EW exhibited the highest DPPH^•, ABTS^•+ and O₂^•−-scavenging activity (EC₅₀ = 0.2999 mg/mL, 67.6597 μg/mL and 5.99 mg/mL, respectively) and reducing power (EC₅₀ = 4.61 mg/mL), while γ-EEW demonstrated the highest iron-chelating activity (76.22%). Thus, the synthesized mixture may be used as a potential source of antioxidant peptides for food and nutraceutical applications.