Mechanism interpretation of Guhan Yangshengjing for protection against Alzheimer's disease by network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Guhan Yangshengjing (GHYSJ) is an effective prescription for delaying progression of Alzheimer's disease (AD) based on the ancient Chinese medical classics excavated from Mawangdui Han Tomb. Comprising a combination of eleven traditional Chinese herbs, the precise protective mechanism through which GHYSJ acts on AD progression remains unclear and has significant implications for the development of new drugs to treat AD. AIM OF THE STUDY: To investigate the mechanism of GHYSJ in the treatment of AD through network pharmacology and validate the results through in vitro experiments. MATERIALS AND METHODS: Chemical composition-target-pathway network and protein-protein interaction network were constructed by network pharmacology to predict the potential targets of GHYSJ for the treatment of AD. The interaction relationship between active ingredients and targets was verified by molecular docking and molecular force. Furthermore, the chemical constituents of GHYSJ were analyzed by LC-MS and HPLC, the effects of GHYSJ on animal tissues were analyzed by H&E staining. An Aß-induced SH-SY5Y cellular model was established to validate the core pathways and targets predicted by network pharmacology and molecular docking. RESULTS: The results of the network pharmacology analysis revealed a total of 155 bioactive compounds capable of crossing the blood-brain barrier and interacting with 677 targets, among which 293 targets specifically associated with AD, which mainly participated in and regulated the amyloid aggregation pathway and PI3K/Akt signaling pathway, thereby treating AD. In addition, molecular docking analysis revealed a robust binding affinity between the principal bioactive constituents of GHYSJ and crucial targets implicated in AD. Our findings were further substantiated by in vitro experiments, which demonstrated that Liquiritigenin and Ginsenosides Rh4, crucial constituents of GHYSJ, as well as GHYSJ pharmaceutic serum, exhibited a significant down-regulation of BACE1 expression in Aß-induced damaged SH-SY5Y cells. This study provides valuable data and theoretical underpinning for the potential therapeutic application of GHYSJ in the treatment of AD and secondary development of GHYSJ prescription. CONCLUSION: Through network pharmacology, molecular docking, LC-MS, and cellular experiments, GHYSJ was initially confirmed to delay the progression of AD by regulating the expression of BACE1 in Amyloid aggregation pathway. Our observations provided valuable data and theoretical underpinning for the potential therapeutic application of GHYSJ in the treatment of AD.

The latest advances in high content screening in microfluidic devices.

INTRODUCTION: High content screening (HCS) is an important tool for drug screening. However, the potential of HCS in the field of drug screening and synthetic biology is limited by traditional culture platforms that use multi-well plates, which have several disadvantages. Recently, microfluidic devices have gradually been applied in HCS, which significantly reduces experimental costs, increases assay throughput, and improves the accuracy of drug screening. AREAS COVERED: This review provides an overview of microfluidic devices for high-content screening in drug discovery platforms, including droplet, microarray, and organs-on-chip technologies. EXPERT OPINION: HCS is a promising technology increasingly adopted by the pharmaceutical industry as well as academic researchers for drug discovery and screening. In particular, microfluidic-based HCS shows unique advantages, and microfluidics technology has promoted significant advancements and broader usage and applicability of HCS in drug discovery. With the integration of stem cell, gene editing technology, and other biological technologies, microfluidics-based HCS will expand the application scope of personalized disease and drug screening models. The authors anticipate rapid developments in this field, with microfluidic-based approaches becoming increasingly important in HCS applications.