RESUMEN
Nonalcoholic fatty liver disease (NAFLD) has developed into the most common chronic liver disease and can lead to liver cancer. Our laboratory previously developed a novel prescription for NAFLD, "Eight Zhes Decoction" (EZD), which has shown good curative effects in clinical practice. However, the pharmacodynamic material basis and mechanism have not yet been revealed. A strategy integrating lipidomics, network pharmacology and pharmacokinetics was used to reveal the active components and mechanisms of EZD against NAFLD. The histopathological results showed that EZD attenuated the degrees of collagen deposition and steatosis in the livers of nonalcoholic steatofibrosis model mice. Furthermore, glycerophospholipid metabolism, arachidonic acid metabolism, glycerolipid metabolism and linoleic acid metabolism with phospholipase A2 group IVA (PLA2G4A) and cytochrome P450 as the core targets and 12,13-cis-epoxyoctadecenoic acid, 12(S)-hydroxyeicosatetraenoic acid, leukotriene B4, prostaglandin E2, phosphatidylcholines (PCs) and triacylglycerols (TGs) as the main lipids were found to be involved in the treatment of NAFLD by EZD. Importantly, naringenin, artemetin, canadine, and bicuculline were identified as the active ingredients of EZD against NAFLD; in particular, naringenin reduces PC consumption by inhibiting the expression of PLA2G4A and thus promotes sufficient synthesis of very-low-density lipoprotein to transport excess TGs in the liver. This research provides valuable data and theoretical support for the application of EZD against NAFLD.
RESUMEN
Yangyinqingfei Decoction (YYQFD), a traditional Chinese prescription, is well known in the treatment of diphtheria and lung-related diseases in clinic. However, whether it can be used to block the lung injury caused by air pollutant remains unclear. In the present study, the effect of YYQFD was addressed using a PM2.5-induced lung injury mice model. It was shown that YYQFD significantly improved pulmonary functions of mice exposed to PM2.5, the levels of IL-6, TNF-α and MDA were decreased while SOD levels were increased in serum and bronchoalveolar fluid. The potential mechanism of YYQFD was then delved using metabolomic and proteomic techniques. The protein-metabolite joint analysis showed that YYQFD regulated the biosynthesis of unsaturated fatty acids, linoleic acid and arachidonic acid metabolism, causing a significant decrement of pro-inflammatory mediator arachidonic acid with its downstream metabolites like 20-HETE, prostaglandin E2, accompanied by the up-regulation of PTGES2, GPX2 and CBR3 in lung tissue. These data were used to construct a regulatory metabolic network map in terms of the therapeutic role of YYQFD in PM2.5-induced lung injury, thereby provided a novel insight into potential application in the respiratory diseases caused by air pollutants.
RESUMEN
Alzheimer's disease (AD) is a common and serious neurodegenerative disease in the elderly; however, the treatment of AD is still lacking of rational drugs. In this paper, the active constituents and targets of the self-developed Chinese medicine Formula 9002A in the treatment of AD were investigated from three aspects: pharmacodynamics based on cell and animal experiments, network pharmacology analysis, and pharmacokinetic analysis. A total of 124 compounds were screened in Formula 9002A, and four constituents including salidroside, gastrodin, niacinamide, and umbelliferone were screened as potential active components for the treatment of AD by network pharmacology. Among them, salidroside and gastrodin showed higher relevance with AD targets, such as ESR1 and AR. The pharmacokinetic study showed that they could be absorbed and identified in plasma; the half-life and mean residence times of salidroside and gastrodin in plasma were nearly increased 2-fold by the administration of Formula 9002A compared with those by the administration of a monomer, indicating the extended action time of active compounds in vivo. Formula 9002A exerted the efficacy in the treatment of AD mainly by regulating APP, GSK3ß, ESR1, and AR targets based on the anti-ß-amyloid protein deposition, anti-oxidation and anti-apoptosis pathways. Two genes enriched in Alzheimer's disease pathway, APP and GSK3ß, were further validated. The experiments also demonstrated that Formula 9002A could downregulate APP and GSK3ß protein expression in the model mice brain and improved their cognitive ability. In summary, Formula 9002A has the characteristics of multiple targets and multiple pathways in the treatment of AD, and salidroside and gastrodin might be the main active constituents, which could provide a foundation for further research and application.