GSZ Formula Enhances Sleep Quality:Exploring Its Active Ingredients and Mechanism Using a Network Medicine Approach

Background:Sleep is essential for maintaining human health,and insomnia is a widespread problem.Traditional Chinese medicine(TCM)has been used for centuries to treat sleep disorders,with fewer reported side effects compared to conventional treatments.Objective:This study seeks to investigate the sleep-promoting effects of the GSZ formula,which comprisesγ-aminobutyric acid(GABA),Schisandrae Chinensis Fructus(Wuweizi in Chinese),and Ziziphi Spinosae Semen(Suanzaoren in Chinese).In addition,this study aims to explore the active ingredients and potential mechanisms underlying the sleep-enhancing effects of the formula.Methods:The impact of GSZ on sleep was evaluated using two models,the complete sleep model and the sub-threshold sleep model.Mice were randomly divided into five groups and orally administered GSZ solution(0.33 g/kg/day or 0.99 g/kg/day),positive drug diazepam(2.50 mg/kg)or a control solution for 30 days.Hypno-sis model was established in mice using pentobarbital sodium.Sleep duration and incidence were measured by recording when the righting reflex of mice disappeared for more than 1 min.GABA and dopamine(DA)levels in mouse brain tissue were measured using ELISA kits.The ingredients of the GSZ formula were identified using mass spectrometry,and the targets of these ingredients and disease-related genes were retrieved from public databases.A network medicine approach was used to calculate the shortest path between ingredient targets and disease-related proteins.The expression levels of potential proteins,such as Akt,p-Akt,GSK-3β,and p-GSK-3β,were analyzed using Western blotting based on the predicted results.Results:GSZ significantly prolonged sleep duration and enhanced the sleep rate in mice(P<0.05).Furthermore,it elevated GABA levels and reduced DA levels in the mouse brain(P<0.05).Network medicine analysis suggested that GABA,stearic acid,genistin,and coumestrol may be the most crucial active ingredients for sleep improve-ment.Western blotting analysis demonstrated that GSZ modulated the protein expression levels of p-Akt/Akt and p-GSK-3β/GSK-3β(P<0.05).Conclusion:Our study demonstrated that the GSZ formula could improve sleep,with key ingredients likely being GABA,stearic acid,genistin,and coumestrol.The mechanism might involve the regulation of the Akt/GSK-3βpathway,as revealed by the network medicine analysis and experimental validation.Our current new findings shed light on the potential mechanisms underlying the sleep-enhancing effects of the GSZ formula,which could provide experimental evidence to develop innovative treatments for insomnia.

Pt/Zn heterostructure as efficient air-electrocatalyst for long-life neutral Zn-air batteries

Neutral Zn-air batteries(ZABs) have attracted much attention due to the enhanced lifespan and stability.However, their development is suppressed by the poor catalytic properties of the air-electrocatalysts for oxygen reduction reaction(ORR) and oxygen evolution reaction(OER). Hence,the exploration of highly efficient electrocatalysts for neutral ZABs is critical. Herein, we designed an economical heterostructure of Pt nanoparticle-modified Zn nanoplates(Pt/Zn NPs). Compared with commercial Pt/C electrocatalyst, our Pt/Zn heterostructure exhibits comparable catalytic properties and ultrahigh stability in neutral media. The heterostructure can reduce the dosage of Pt and offer sufficient active sites,resulting in enhanced catalytic properties for ORR/OER in neutral media. When applied to neutral ZABs as air cathode,our heterostructure exhibits a high power density of 45 mW cm^(-2) and excellent stability of more than 850 cycles with negligible decay, making it the most efficient and robust one in neutral electrolyte. This approach opens a new avenue to strategically design catalysts with high activity for neutral ZABs, rendering them potential in portable and wearable electronic devices.