Integrated serum pharmacochemistry and network pharmacology to explore the mechanism of Yi-Shan-Hong formula in alleviating chronic liver injury.

BACKGROUND: Chronic liver injury (CLI) is a complex condition that requires effective therapeutic interventions. The Yi-Shan-Hong (YSH) formula is an empirically derived remedy that has shown effectiveness and safety in the management of chronic liver damage. However, the bioactive components and multifaceted mechanisms of YSH remain inadequately understood. PURPOSE: To examine the bioactive compounds and functional processes that contribute to the therapeutic benefits of YSH against CLI. METHODS: Serum pharmacochemistry and network pharmacology were employed to identify active compounds and possible targets of YSH in CLI. In addition, YSH was also given in three doses to d-(+)-galactosamine hydrochloride (D-GalN) -induced CLI rats to test its therapeutic efficacy. RESULTS: The analysis of serum samples successfully detected 25 compounds from YSH. Searches on the databases resulted in 277 genes as being correlated with chemicals in YSH, and 397 genes associated with CLI. In vivo experiments revealed that YSH displayed a notable therapeutic impact on liver injury caused by d-GalN. This was evidenced by enhanced liver function and histopathological improvements, reduced oxidative stress response, proinflammatory factors, and fibrosis levels. Importantly, no discernible adverse effects were observed. Furthermore, the administration of YSH treatment reversed the activation of AKT phosphorylation caused by d-GalN, aligning with the findings of the network pharmacology study. CONCLUSION: These findings provide preclinical evidence of YSH's therapeutic value in CLI and highlight its hepatoprotective action via the PI3K/AKT signaling pathway.

Novel electro-assisted micro-aerobic cathode biological technology induces oxidative demethylation of N, N-dimethylformamide for efficient ammonification of refractory membrane-making wastewater.

Recalcitrant and toxicological membrane-making wastewater displays negative impacts on environment, and this is difficult to treat efficiently using conventional hydrolytic acidification. In this study, a novel electro-assisted biological reactor with micro-aerobic cathode (EABR-MAC) was developed to improve the biodegradation and ammonification of N, N-dimethylformamide (DMF) in membrane-making wastewater, and the metabolic mechanism using metagenomic sequencing as comprehensively illustrated. The results showed that EABR-MAC significantly improved the ammonification of refractory organonitrogen and promoted DMF oxidative degradation by driving the electron transferred to the cathode. Additionally, the inhibition rates of oxygen uptake rate and nitrification in EABR-MAC were both lower under different cathode aeration frequency conditions. Microbial community analysis indicated that the functional fermentation bacteria and exoelectrogens, which were correlated with COD removal, ammonification, and detoxification, were significantly enriched upon electrostimulation, and the positive biological connections increased to form highly connected communities instead of competition. The functional genes revealed that EABR-MAC forcefully intervened with the metabolic pathway, so that DMF converted to formamide and ammonia by oxidative demethylation and formamide hydrolysis. The results of this study provide a promising strategy for efficient conversion of organonitrogen into ammonia nitrogen, and offer a new insight into the effects of electrostimulation on microbial metabolism.