Moringa oleifera Lam. Isothiocyanate Quinazolinone Derivatives Inhibit U251 Glioma Cell Proliferation through Cell Cycle Regulation and Apoptosis Induction.

A major active constituent of Moringa oleifera Lam. is 4-[(α-L-rhamnose oxy) benzyl] isothiocyanate (MITC). To broaden MITC's application and improve its biological activity, we synthesized a series of MITC quinazolinone derivatives and evaluated their anticancer activity. The anticancer effects and mechanisms of the compound with the most potent anticancer activity were investigated further. Among 16 MITC quinazolinone derivatives which were analyzed, MITC-12 significantly inhibited the growth of U251, A375, A431, HCT-116, HeLa, and MDA-MB-231 cells. MITC-12 significantly inhibited U251 cell proliferation in a time- and dose-dependent manner and decreased the number of EdU-positive cells, but was not toxic to normal human gastric mucosal cells (GES-1). Further, MITC-12 induced apoptosis of U251 cells, and increased caspase-3 expression levels and the Bax:Bcl-2 ratio. In addition, MITC-12 significantly decreased the proportion of U251 cells in the G1 phase and increased it in S and G2 phases. Transcriptome sequencing showed that MITC-12 had a significant regulatory effect on pathways regulating the cell cycle. Further, MITC-12 significantly decreased the expression levels of the cell cycle-related proteins CDK2, cyclinD1, and cyclinE, and increased those of cyclinA2, as well as the p-JNK:JNK ratio. These results indicate that MITC-12 inhibits U251 cell proliferation by inducing apoptosis and cell cycle arrest, activating JNK, and regulating cell cycle-associated proteins. MITC-12 has potential for use in the prevention and treatment of glioma.

Isolation, Identification, Activity Evaluation, and Mechanism of Action of Neuroprotective Peptides from Walnuts: A Review.

As human life expectancy increases, the incidence of neurodegenerative diseases in older adults has increased in parallel. Walnuts contain bioactive peptides with demonstrated neuroprotective effects, making them a valuable addition to the diet. We here present a comprehensive review of the various methods used to prepare, isolate, purify, and identify the neuroprotective peptides found in walnuts. We further summarise the different approaches currently used to evaluate the activity of these peptides in experimental settings, highlighting their potential to reduce oxidative stress, neuroinflammation, and promote autophagy, as well as to regulate the gut microflora and balance the cholinergic system. Finally, we offer suggestions for future research concerning bioavailability and improving or masking the bitter taste and sensory properties of final products containing the identified walnut neuroprotective peptides to ensure successful adoption of these peptides as functional food ingredients for neurohealth promotion.

Walnut Protein Peptides Ameliorate DSS-Induced Ulcerative Colitis Damage in Mice: An in Silico Analysis and in Vivo Investigation.

Walnut (Juglans regia L.) is a food with food-medicine homology, whose derived protein peptides have been shown to have anti-inflammatory activity in vitro. However, the effects and mechanisms of walnut protein peptides on ulcerative colitis (UC) in vivo have not been systematically and thoroughly investigated. In this study, we applied virtual screening and network pharmacology screening of bioactive peptides to obtain three novel WPPs (SHTLP, HYNLN, and LGTYP) that may alleviate UC through TLR4-MAPK signaling. In vivo studies have shown that WPPs improve intestinal mucosal barrier dysfunction and reduce inflammation by inhibiting activation of the TLR4-MAPK pathway. In addition, WPPs restore intestinal microbial homeostasis by reducing harmful bacteria (Helicobacter and Bacteroides) and increasing the relative abundance of beneficial bacteria (Candidatus_Saccharimonas). Our study showed that the WPPs obtained by virtual screening were effective in ameliorating colitis, which has important implications for future screening of bioactive peptides from medicinal food homologues as drugs or dietary supplements.

Moringa oleifera Lam. Peptide Remodels Intestinal Mucosal Barrier by Inhibiting JAK-STAT Activation and Modulating Gut Microbiota in Colitis.

Ulcerative colitis is a chronic inflammatory bowel disease (IBD), but progress in exploring its pathogenesis and finding effective drugs for its prevention and treatment has stalled in recent years. The seeds of Moringa oleifera Lam. are rich in proteins known to have multiple physiological activities. In our earlier work, we had isolated and purified a peptide (MOP) having the sequence KETTTIVR, from M. oleifera seeds; however, its anti-inflammatory activity and mechanism in vivo were unclear. Here we used the dextran sulfate sodium (DSS)-induced colitis model to study the anti-inflammatory activity and mechanism of this MOP. Our results are the first to show that MOP can ameliorate the pathological phenotype, inflammation, and intestinal barrier disruption in mice with colitis. Furthermore, RNA sequencing revealed that MOP inhibits the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway activation. Next, by using 16s rRNA gene sequencing, we found that MOP can ameliorate DSS-induced gut microbiota dysbiosis. In addition, an untargeted metabolomics analysis suggested that MOP is able to modulate the level of lipid and amino acid metabolites in IBD-stricken mice. Altogether, these results indicate that MOP ameliorates colitis by remodeling intestinal mucosal barrier by inhibiting JAK-STAT pathway's activation and regulating gut microbiota and its metabolites, thus providing a basis for further processing and design of bioactive foods from M. oleifera seeds.