The aim of this study was to explore the protective mechanism of WLY-0, a polysaccharide extracted from Huangshui, on the intestinal barrier by RNA sequencing (RNA-seq) using the Caco-2 cell model. The results showed that the differential genes between the WLY-0 treatment group and the lipopolysaccharide (LPS)-induced injury group were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway. Subsequently, Western blot was used to verify the effect of WLY-0 on the expression of key proteins in the MAPK signaling pathway. It was found that the addition of WLY-0 significantly inhibited the phosphorylation of p38 and c-Jun N-terminal kinase (JNK) and promoted the phosphorylation of extracellular signalregulated kinase (ERK) (P < 0.05). Meanwhile, the mRNA expression of the downstream pro-inflammatory factors IL-6, TNF-α, and IL-8 decreased by 53.34%, 44.56%, and 37.16%, respectively, while those of the anti-inflammatory factors IL-10 and IL-37 increased by 6.96 and 19.54 times, respectively. These results indicated that WLY-0 protects against LPS-induced intestinal barrier injury by altering the expression of inflammation-related genes through the regulation of the MAPK-mediated anti-inflammatory signaling pathway. This conclusion provides a theoretical basis for developing adjuvant therapeutic products based on Huangshui polysaccharides for inflammatory bowel disease.

Antioxidant peptides have been widely reported. However, only a few reports have been published examining the antioxidant peptides derived from Chinese baijiu. In this study, 6 novel peptides derived from Chinese baijiu were identified successfully using high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (HPLC-QTOF-MS) with a concentration of 0.835–24.540 µg/L. The underlying molecular mechanisms were investigated, and their cytoprotective effects were examined against 2,2’-azobis (2-methylpropanimidamidine) dihydrochloride (AAPH)-induced oxidative stress in HepG2 cells. The results showed that these peptides exerted protective effects by suppressing reactive oxygen species (ROS) generation, preventing malondialdehyde (MDA) formation, and upregulating cellular antioxidant enzyme activities (SOD, CAT, and GSH-Px) in a dose-dependent manner. Further experiments proved that these peptides exerted antioxidant effects via Nrf2/ARE-mediated signaling pathway by promoting Nrf2 nuclear translocation, inhibiting ubiquitination, and enhancing transcription capacity of Nrf2 in HepG2 cells. These findings provide the molecular basis for the effects of antioxidant peptides derived from Chinese baijiu, which is important for a deeper understanding of the relationship between human health and moderate drinking.