The incidence of depressive disorders has steadily increased, with factors such as social stress, neuroinflammation, and gut dysbiosis contributing to the intricate pathogenesis of depression. Traditional antidepressants often exhibit limited efficacy and are accompanied by pharmacological side effects. Moringa isothiocyanate-1 (MITC-1), a food-medicinal active substance isolated from moringa seeds, has demonstrated anti-inflammatory and neuroprotective properties. However, the potential effects and the mechanism of MITC-1 on neuroinflammation associated with depression remain unclear. In this study, we characterized aberrant activation of microglia induced by lipopolysaccharides (LPS) and demonstrated that MITC-1 has a protective effect on gut dysbiosis and neuroinflammation. We found that in MITC-1 treated mice, neuroinflammation was attenuated, evidenced by increased interest in sucrose and food rewards, reduced ingestion latency, enhanced novel object recognition, and improved voluntary activity and social behaviors. Subsequently, fecal microbiota transplantation (FMT) models were also established in mice, primarily focusing on behavioral aspects and intestinal function evaluations. We found fecal microbiota transplantation from MITC-1 treated mice facilitated the reconstruction of gut microbiota in LPS-induced mice. Ultimately, integrative approaches utilizing gut microbiome and metabolomics technology analyses, coupled with neuroglial morphology assessments, were employed to uncover the preventive mechanisms of MITC-1 against inflammatory depression. Our results revealed that oral administration of MITC-1 significantly altered the fecal microbiota composition, up-regulated the tryptophan (Trp) metabolic pathway, and inhibited neuronal loss and microglial activation, thereby, ameliorating mood, cognition function, and behaviors. In summary, MITC-1 mediated the microbiota-gut-brain axis through the Trp metabolic pathway, restructuring gut microbes and reducing neuroinflammation.

People living long-term in areas with UV will cause premature photoaging. An abnormal reduction in autophagy is a key feature of photoaging, and p38 MAPK has been regarded as a key regulator of autophagy. Isothiocyanate is one of the main active components of Moringa oleifera Lam. seeds. Studies have reported that M. oleifera Lam. seeds isothiocyanate (MITC) has anticancer, anti-inflammatory, cardiometabolic repair, nervous system protection, blood lipid regulation and diabetes prevention properties. However, the molecular mechanisms of MITC with protective effects against skin photoaging have not been studied thus far. In this study, we aimed to evaluate the antiphotoaging activity of MITC and to investigate the effect of p38 MAPK-dependent autophagy in vivo and in vitro models of photoaging. In this research we found that MITC can reverse the intracellular reactive oxygen species (ROS) content and inhibit the activation of p38 MAPK to improve the autophagy level, reduce the expression of matrix metalloproteinases (MMPs), and finally protect against photoaging by UV. Our results will uncover the molecular mechanisms of MITC that play a role in the protective effects against skin photoaging, provide helpful information for developing MITC as an anti-photoaging plant material and improve the utilization of M. oleifera Lam. seeds.

Walnut dreg protein hydrolysates (WDPHs) exhibit a variety of biological activities, however, the cyclooxygenase-2 (COX-2) inhibitory peptide of WDPHs remain unclear. The aim of this study was to rapidly screen for such peptides in WDPHs through a combination of in silico and in vitro analysis. In total, 1262 peptide sequences were observed by nano liquid chromatography/tandem mass spectrometry (nano LC-MS/MS) and 4 novel COX-2 inhibitory peptides (AGFP, FPGA, LFPD, and VGFP) were identif ied. Enzyme kinetic data indicated that AGFP, FPGA, and LFPD displayed mixed-type COX-2 inhibition, whereas VGFP was a non-competitive inhibitor. This is mainly because the peptides form hydrogen bonds and hydrophobic interactions with residues in the COX-2 active site. These results demonstrate that computer analysis combined with in vitro evaluation allows for rapid screening of COX-2 inhibitory peptides in walnut protein dregs.