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.
Fuzhuan brick tea is a dark tea produced using tea plant leaves, and its quality is strongly affected by Eurotium cristatum. The superior Eurotium cristatum strain could enhance functional components in Fuzhuan brick tea, improving its quality and economic value. To research the lipid-lowering substance of Eurotium cristatum in Fuzhuan brick tea from Anhua country tea production area, several wild-type Eurotium cristatum strains were screened for lovastatin production. Of all 20 wild-type strains, 6 Eurotium cristatum strains could produce lovastatin, and the H20 test strain could produce the highest lovastatin. The organ of lovastatin production was studied, and its yield in sexual propagule (ascospore and ascocarp) was the highest. Some fermentation parameters for lovastatin produced by the H20 strain were researched, and the optimum condition, such as PDA medium containing additional 8% soluble starch, 32 °C, and 120 r/min, are reported. These results are promising for developing one Fuzhuan brick tea with a high lipid-lowering function and expanding the scope of tea plant forest resource application.
The tea plant is a vital strategic forest resource in China. Dark tea produced from its leaves is an indispensable health-promoting product in western China due to its unique lipid-lowering function. Eurotium cristatum is the dominant strain in Fuzhuan brick tea (a variety of Anhua dark tea) and could produce many functional components, including lovastatin, a lipid-lowering compound. In this study, the lovastatin yield of dark tea was improved by breeding Eurotium cristatum using the protoplast fusion method. The experiments were carried out by inducing a fusion between inactivated Eurotium cristatum JH1205 and Monascus CICC5031. Among the 92 fusants screened the HPLC method, four strains (A4, A36, A54, and A76) with higher lovastatin production (more than three times as high) were obtained. The A76 strain had the highest lovastatin yield, which was 23.93 μg/mL. The location of the tea forest strongly influenced the lovastatin yield of loose dark tea. The strain bred in this study improved the lovastatin yield of loose dark tea by more than three times when compared to wild Eurotium cristatum. These results are promising for the development of tea forest resources.