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

Abstract

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.

Moringa oleifera leaf polysaccharide alleviates experimental colitis by inhibiting inflammation and maintaining intestinal barrier

“…Additionally, administration reduced tissue MPO activity and serum LPS levels in the DSS + MOLP-M and DSS + MOLP-H groups when compared to the DSS group. This is in line with the results of Hong et al ( 27 ), which indicated that a high dose of (MOP) decreased MPO in the serum of DSS-induced UC mice. These findings suggest that MOLP plays a protective role against DSS-induced UC by inhibiting MPO activity and serum LPS levels.…”

“…And also neutrophils are one of the infiltrating cells that cause inflammation in colitis ( 26 ). This is consistent with the findings of Hong et al ( 27 ), which indicated that a high dose of (MOP) extracted and purified a peptide from M. oleifera seeds significantly reduced such mucosal damage (including the greater crypt depth), decreased in goblet cells and inflammatory cell infiltration, leading to lower histological scores in DSS-induced UC mice. Therefore, these results showed that MOLP supplementation could improve the histopathological changes in DSS-induced UC.…”

“…However, the medium and high doses of MOLP administration maintained the expression and distribution of these two proteins. Previous research ( 27 ) found that MOP reduced the levels of occludin and ZO-1 in DSS-induced UC mice. These findings indicated that the protective roles of MOLP in the intestinal epithelium may be associated with its ability to improve compromised TJs in DSS-induced UC.…”

A quinoa peptide protects impaired mucus barriers in colitis mice by inhibiting NF-κB-TRPV1 signaling and regulating the gut microbiota

“…seeds improved the pathological phenotype and inflammation in colitis mice by inhibiting the JAK/STAT signaling pathway. 30 Integrity of the intestinal barrier plays an important role in inhibiting NF-κB signaling activation. The study has demonstrated that enhancing intestinal barrier integrity can lead to decreased NF-κB signaling.…”

“…For instance, the peptide KETTTIVR significantly increases the relative abundances of Lachnospira , Blautia , and Ruminococcus . 30 Bacteroides , Blautia , and Lachnospiraceae_NK4A136 are genera of probiotics that produce short-chain fatty acids, which regulate host health and alleviate inflammatory diseases. 37 In comparison with the DSS group, TPGAFF intervention led to a notable increase of Bacteroides , Blautia , and Lachnospiraceae_NK4A136 .…”