Natural compound-based treatments provide innovative ways for ulcerative colitis therapy. However, poor targeting and rapid degradation curtail its application, which needs to be addressed. Inspired by biomacromolecule-based materials, we have developed an orally administrated nanoparticle (GBP@HA NPs) using bovine serum albumin as a carrier for polyphenol delivery. The system synergizes galactosylated bovine serum albumin with two polyphenols, epigallocatechin gallate and tannic acid, which is then encased in “nanoarmor” of ε-Polylysine and hyaluronic acid to boost its stability and targeting. Remarkably, the nanoarmor demonstrated profound therapeutic effects in both acute and chronic mouse models of ulcerative colitis, mitigating disease symptoms via multiple mechanisms, regulating inflammation related factors and exerting a modulatory impact on gut microbiota. Further mechanistic investigations indicate that GBP@HA NPs may act through several pathways, including modulation of Keap1-Nrf2 and NF-κB signaling, as well as Caspase-1-dependent pyroptosis. Consequently, this novel armored nanotherapy promotes the way for enhanced polyphenol utilization in ulcerative colitis treatment research.
Yanfang Yu,Yuhuan Chen,Xuping Shi,Chuan Ye,Junwen Wang,Jinzhi Huang,Bing Zhang,Zeyuan Deng
This study investigated the hepatoprotective effects of various mulberry (Morus alba L.) leaf extracts (MLEs), including mulberry ethanol extract (MEE), aqueous extract (MAE) and a combination extract (MCE) against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury in rats. It aimed to explore the possible molecular mechanism of the liver-protecting function of mulberry leaves and provide a reference for choosing the appropriate extraction method. The results showed that the three extracts contained different amounts of phenolic compounds, 1-deoxynojirimycin (DNJ) and polysaccharides. MLEs markedly improved the pathological status of rat liver tissue, decreased the levels of AST, ALT, TNF-α, IL-1β, IL-6 and MDA, while increased the levels of GSH, SOD and CAT in the D-GalN/LPS-treated rats at the same time. MEE, with the highest amount of total phenolics, exhibited the highest antioxidant activity corresponding to the protein expression level of Nrf2 and HO-1. MCE significantly suppressed the expression of apoptosis-related dot-like protein (ASC) and Caspase-1 and inhibited the phosphorylation of p38 MAPK and ERK1/2, thereby showing high anti-inflammatory activity. These results indicated that the active components from mulberry leaves protected rats against acute liver injury, attributed to a reduction in both oxidative stress and inflammatory response. The protective effect may be implicated in regulating the Nrf2, NLRP3 and MAPK signaling pathways.