ABSTRACT
Zearalenone (ZEN), a ubiquitous mycotoxin that widely occurs in grain and foodstuff may induce serious toxic effects after accumulation in vivo. Melanoidins (MLDs) have shown multiple bio-functional properties such as antioxidant, anti-bacterial and prebiotic activities. Black garlic exhibits several advantages over fresh garlic related to health improvement. In this study, the alleviative effects of black garlic MLDs on ZEN-induced toxicity and the potential mechanisms were studied using zebrafish embryonic developmental model. The results showed that MLDs restored the ZEN-induced adverse influences on zebrafish embryonic development, including delay in hatching time, morphological abnormality and the impairment of nervous development. Further studies showed that MLDs significantly inhibited the ZEN-induced production of reactive oxygen species (ROS) and enhanced the intrinsic antioxidant ability by increasing the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and the content of glutathione (GSH). In addition, co-exposure of MLDs significantly inhibited the ZEN-stimulated cellular apoptosis in zebrafish larvae through down-regulation of pro-apoptotic genes of bax, caspase-3 and caspase-9 and up-regulation of anti-apoptotic gene bcl-2. Moreover, MLDs inhibited the in vivo accumulation of ZEN in zebrafish larvae. To sum up, MLDs attenuated the ZEN-induced zebrafish embryonic developmental toxicity through suppression of the oxidative stress and intervention on mitochondria apoptosis pathway as well as inhibiting the absorption of ZEN in zebrafish embryos/larvae. The results suggest that black garlic MLDs have potential to be used as a functional ingredient against the adverse effects of exogenous toxins.
Subject(s)
Garlic , Zearalenone , Animals , Antioxidants/pharmacology , Zearalenone/toxicity , Zebrafish , Oxidative Stress , Glutathione , Embryonic Development , ApoptosisABSTRACT
Plant-derived exosome-like nanovesicles play an important role in transferring their biological cargos to recipient cells. The effect of garlic-derived exosome-like nanovesicles (GENs) against inflammatory bowel disease (IBD) remains unknown. This study aimed to investigate the effect of GENs on dextran sulphate sodium (DSS)-induced colitis in mice. A comprehensive analysis of bioactive components in GENs was performed. Data showed that GENs contained 26 lipids, 61 proteins and 127 known microRNAs (miRNAs). Han-miR3630-5p in GENs could bind to the 3' untranslated region of toll-like receptor 4 (TLR4), which led to the inhibition of TLR4 expression. Besides, GENs significantly up-regulated the expression of barrier-related proteins and inhibited the overproduction of pro-inflammatory cytokines in LPS-induced Caco-2 cells. As a result, pretreatment with GENs at 100 mg kg-1 efficiently ameliorated the inflammatory bowel behavior, intestinal histological pathological damage, and tight junction protein dysfunction induced by DSS in the colon tissue. Intake of GENs significantly down-regulated the expressions of TLR4, myeloid differentiation primary response gene 88 (MyD88), and nuclear factor kappa-B (NF-κB), which suppressed the downstream cascades and led to less secretion of pro-inflammatory cytokines induced by DSS. Furthermore, pretreatment with GENs altered the gut microbiota profile of colitis mice by recovering the relative abundance of Lachnospiraceae and reducing the relative abundance of Helicobacter. Totally, GENs had potential to protect the colon against DSS-induced damage through inhibiting the TLR4/MyD88/NF-κB signaling pathway and regulating gut microbiota. This study clarified the role of miRNAs of GENs in anti-colitis and proved that GENs had a potential application for IBD prevention.