Non-alcoholic steatohepatitis (NASH), a progressive liver disease characterized by lipid accumulation and chronic inflammation, lacks effective therapies targeting its multifactorial pathogenesis. This study investigates marine-derived chondroitin sulfate (CS) as a multi-organelle modulator capable of regulating lipid metabolism, oxidative stress, and inflammation in NASH. By employing subcellular imaging and organelle-specific labeling techniques, we demonstrate that CS restores lysosomal acidification in a NASH model, enabling the reduction of lipid droplets via lysosomal–lipid droplet fusion. Concurrently, CS upregulates dynamin-related protein 1 (DRP1), driving mitochondrial terminal fission to spatially isolate reactive oxygen species (ROS) segments for mitophagy, thereby reducing ROS levels. Notably, pharmacological inhibition of lysosomal activity using chloroquine or bafilomycin A1 abolished the therapeutic effects of CS, confirming lysosomal acidification as an essential prerequisite. Collectively, these findings reveal the potential of CS as a therapeutic agent for NASH and provide critical insights into the subcellular mechanisms underlying its protective effects, thus offering a foundation for future research and therapeutic development.

Skin photoaging, marked by structural and functional changes, is mainly caused by long-term ultraviolet (UV) exposure. This study sought to create hydroxytyrosol (HT)-loaded soluble microneedles (HT MNs) and thoroughly assess their anti-photoaging effects and underlying mechanisms in vitro and in vivo. The optimized HT MNs, featuring tips with 10% HT + 5% hyaluronic acid (HA) and a backing layer of 10% polyvinyl pyrrolidone (PVP), demonstrated robust mechanical strength (withstanding an axial force of 10 N without fracture), adequate penetration depth (>200 μm), and efficient skin self-recovery post-removal. In vitro, HT MNs notably boosted cell viability, reduced reactive oxygen species (ROS) levels, and suppressed senescence-associated β-galactosidase (A-β-Gal) expression in UVA-exposed human skin fibroblasts (HSF). In vivo, in a UVA + UVB-irradiated mouse model, HT MNs significantly enhanced skin hydration and elasticity, increased collagen density (confirmed by Masson staining), decreased malondialdehyde (MDA) content, and elevated the activities of glutathione (GSH), catalase (CAT), and glutathione peroxidase (GSH-Px). Western blot analysis further revealed that HT MNs upregulated the expression of collagen type I alpha 1 (COL1A1), elastin (ELN), hyaluronan synthase 2 (HAS2), and filaggrin (FLG), while downregulating matrix metalloproteinase 1. Overall, these findings suggest that HT MNs effectively mitigate UV-induced photoaging through antioxidant, anti-senescence, and extracellular matrix (ECM)-regulating mechanisms, underscoring their potential as a novel transdermal anti-photoaging therapy.

Parkinson’s disease (PD), a debilitating neurodegenerative disorder, is primarily characterized by motor impairments and concurrent gastrointestinal disturbances. Increasing evidence has highlighted the critical role of the microbiota–gut–brain axis (MGBA) in the pathogenesis of PD. This study investigated the neuroprotective potential of sodium hyaluronate (SH) in a mouse model of PD and its underlying mechanisms via the MGBA. In the oral pre-treatment study, three doses (7.5, 15, and 30 mg/kg/day) were evaluated. The results showed that the high dose (SH-H, 30 mg/kg/day) significantly ameliorated motor disorders and gastrointestinal functional disorders. Therefore, SH-H was selected for subsequent mechanistic investigations. Mechanistically, SH-H restored gut microbiota homeostasis, increased fecal short-chain fatty acid (SCFA) levels, and improved the integrity of the intestinal and blood–brain barrier (BBB). Thus, SH reduced the transfer of lipopolysaccharide (LPS) from the intestine to serum and the substantia nigra (SN), suppressing activation of the LPS-TLR4/MyD88/NF-κB signaling pathway. These effects alleviated neuroinflammation, protected dopaminergic neurons, and reduced the aggregation of α-synuclein (α-syn). In summary, SH attenuated PD-related pathological changes by restoring gut microbiota homeostasis and modulating the MGBA, suggesting that SH may represent a potential therapeutic strategy for PD.

Inflammation and oxidative stress play important roles in alcohol-induced liver injury. Hyaluronan (HA), a naturally occurring polysaccharide proven to exhibit antioxidant and anti-inflammatory functions, has garnered growing research attention in the field of food in recent years. This study demonstrates that long-term oral administration of HA exerts a protective effect against acute alcohol-induced liver injury (AALI). The findings showed that oral administration of 30, 600, and 1250 kDa HA for 2 and 4 weeks all increased serum and liver HA levels in rats and regulated the composition and abundance of gut microbiota. Meanwhile, oral HA could alleviate the symptoms of liver injury caused by alcohol, including increasing glutathione (GSH) levels, reducing malondialdehyde (MDA) and triglyceride (TG) levels, and decreasing the content of inflammatory factors interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) compared with the AALI model mice. Furthermore, HA could inhibit the increase in reactive oxygen species (ROS) levels in AML12 cells induced by alcohol and improve the survival rate of alcohol-damaged AML12 cells. In conclusion, this study found that oral administration of HA could increase serum and liver HA levels and has a protective effect on AALI, suggesting the application of HA in health foods for hangover relief and liver protection.

Skin aging is a complex physiological process driven by both endogenous and exogenous factors, involving various mechanisms such as oxidative stress, inflammatory responses, and cellular senescence. As natural bioactive macromolecules, plant polysaccharides possess properties including antioxidant, anti-inflammatory, and free radical scavenging abilities, and have recently shown significant potential in anti-skin aging research. This article systematically reviews the molecular mechanisms of skin aging, with a focus on elucidating how plant polysaccharides exert anti-aging effects by regulating key signaling pathways. Additionally, it summarizes strategies for the extraction, purification, and structural modification of plant polysaccharides, as well as their structure–activity relationships. The aim is to provide a theoretical foundation and research directions for both fundamental studies and product development of plant polysaccharides in the field of anti-skin aging.