Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Developing safe and effective strategies to prevent NAFLD progression has become a hot topic. Geraniin is a natural polyphenolic compound abundant in fruit peels and possesses antioxidant and anti-inflammatory activities. This study used a high-fat diet (HFD)-induced NAFLD mouse model to investigate whether geraniin could prevent the development of NAFLD. The results showed that geraniin improved lipid profiles and insulin sensitivity in NAFLD mice, reduced inflammatory factors and oxidative damage, and modulated liver histopathology. mRNA sequencing and Western blot analysis indicated that the beneficial effects of geraniin may be related to the activation of the AMPK/PPAR and NRF2/HO-1 signaling pathways, and the suppression of the NF-u03BAB signaling pathway in the liver. Further liver microRNA sequencing and in vitro experiments revealed that geraniin downregulates miR-34a-5p, thereby upregulating PGC1u03B1 expression, leading to the amelioration of lipid abnormalities and oxidative damage in the liver. Overall, geraniin improved HFD-induced NAFLD in mice through multiple beneficial effects, including antioxidant, anti-inflammatory, and improvement of lipid metabolism and insulin sensitivity, and geraniin ameliorated lipid abnormalities and oxidative damage in NAFLD in part by modulating the miR-34a-5p-PGC1u03B1 axis in the liver. In conclusion, this study shows that geraniin has potential as a natural therapeutic compound for NAFLD in humans.
This study aimed to investigate the effects of trimethylamine N-oxide (TMAO) on vascular calcification (VC) in db/db mice induced by a high-phosphorus diet and to identify the associated molecular pathways. To establish a VC model, db/db mice were fed an adenine-supplemented high-phosphorus diet, with TMAO and its inhibitor 3,3-dimethyl-1-butanol (DMB) administered via drinking water. The effect of TMAO on renal pathology and colonic mucosal barrier function in db/db mice was evaluated. Micro-computed tomography (Micro-CT) and Von Kossa staining were used to evaluate the degree of aortic calcification. Western blotting, immunohistochemistry, immunofluorescence, and RT-qPCR were employed to detect the proteins and mRNAs related to the sirtuin 1 (SIRT1)/nuclear factor-u03BAB p65 (NF-u03BAB p65)/NOD-like receptor pyrin domain-containing 3 (NLRP3) signaling pathway. Sequencing of the 16S rRNA gene was performed to analyse changes in the gut microbiota. We found that the serum TMAO level in db/db-VC model mice was significantly elevated, accompanied by calcium and phosphorus metabolism disorders and gut microbiota imbalance, mainly manifested as an increase in the abundance of Prevotella and Desulfovibrio. TMAO aggravated renal dysfunction and intestinal barrier injury in db/db-VC mice and induced a certain degree of inflammatory response. Moreover, TMAO intervention significantly upregulated the expression of osteogenic marker proteins. In contrast, inhibition of TMAO production by DMB significantly reduced VC. Mechanistically, TMAO inhibited the activity of the SIRT1 deacetylase, promoted the acetylation of NF-u03BAB p65, and subsequently activated its downstream NLRP3 inflammasome and IL-1u03B2 signaling.
Abstract Fructooligosaccharides (FOS) are naturally sourced, low-calorie carbohydrates that resist human digestive enzymes in the gastrointestinal tract. They are selectively fermented by certain Lactobacillus and Bifidobacterium species in the colon, thereby producing short-chain fatty acids (SCFAs). This process promotes the growth of beneficial microbiota while inhibiting pathogenic microorganisms. Consequently, they are classified as prebiotics. By interacting with the gut microbiota, FOS elicit various physiological effects and have attracted considerable research attention in functional food studies due to their favorable physicochemical and biological properties. This review systematically summarizes and critically evaluates recent advances on the physiological functions of FOS, covering their roles in maintaining intestinal microbial balance, reducing plasma levels of cholesterol, phospholipids, and triglycerides, regulating blood glucose levels, and enhancing immunity. Their potential involvement in tumour inhibition and mineral absorption is also discussed. Furthermore, this review examines recent progress in the application of FOS in food systems, including baked goods, meat products, dairy and non-dairy beverages, and animal feed. Special emphasis is placed on emerging in-situ enzymatic conversion technologies, which could enable more flexible and cost-effective utilization of FOS. Additionally, current common biosynthetic strategies are also outlined. Overall, this review highlights the key challenges and future prospects of FOS in functional foods, and provides critical insights for its application in personalized nutrition and disease management.
Abstract Obesity pathogenesis involves a multifaceted interplay between systemic metabolic dysregulation and intestinal microbiota dysbiosis. Using a high-fat diet (HFD)-induced obese mouse model, this research aimed to elucidate the anti-obesity effects and metabolic regulatory functions of Hericium erinaceus polysaccharides (HEP). HEP markedly attenuated weight gain and intrahepatic fat deposition, while enhancing systemic glucose disposal and insulin sensitivity. These metabolic improvements were closely associated with modulation of the hepatic AMPK/SREBP-1c signaling pathway, which downregulated lipogenic genes (FAS, ACC, and SREBP-1c) and enhanced lipid catabolism. The reduced metabolic stress subsequently promoted the organization of epithelial intercellular junctions, as demonstrated by the up-regulation of key barrier proteins, including Occludin, Claudin-1, and ZO-1 and the suppression of TLR4/NF-κB-mediated inflammatory cascades. Notably, HEP treatment remodeled the intestinal microbial landscape by fostering the enrichment of advantageous genera (e.g., Ileibacterium) and suppressing obesity-related bacteria (e.g., Lachnoclostridium). These findings suggested that HEP alleviated obesity by orchestrating a “metabolism-inflammation-microbiota” signaling axis, thereby positioning it as a feasible dietary intervention for the prevention and treatment of obesity.
Abstract Environmental pollution poses a growing threat to male reproductive health. Mono-(2-ethylhexyl) phthalate (MEHP), a pervasive plasticizer metabolite, is known to disrupt male reproductive function through oxidative stress and mitochondrial dysfunction. Extracellular vesicles (EVs) have attracted significant interest as therapeutic biomolecules due to their low immunogenicity and ability to cross biological barriers. In this study, oyster cell membrane vesicles (OCMVs) were successfully prepared through an ultrasound-assisted membrane reassembly strategy. The obtained OCMVs exhibited a relatively uniform particle size of approximately 140 nm and a stable negative zeta potential of approximately -15 mV. Notably, the production yield of OCMVs was approximately 13-fold greater than that of naturally secreted oyster extracellular vesicles (OEVs) isolated by conventional ultracentrifugation. Cellular experiments demonstrated that OCMVs alleviated MEHP-induced oxidative stress by reducing intracellular reactive oxygen species accumulation. In addition, OCMVs attenuated mitochondrial dysfunction and apoptosis, and partially restored the expression of key genes involved in testosterone biosynthesis. OCMVs also reduced DNA damage, as indicated by decreased γ-H2A.X expression. These findings suggest that engineered oyster-derived membrane vesicles may represent a promising biomaterial for alleviating environmental toxicant-induced reproductive cell injury.
