ABSTRACT
Polygonum multiflorum Thunb. (PMT) has shown promise in exerting cerebrovascular protective effects, and its potential for treating ischemic stroke (IS) has garnered attention. However, the lack of clarity regarding its chemical constituents and mechanisms has significantly hindered its clinical application. In this study, we employed network pharmacology and molecular docking techniques for the first time to elucidate the potential compounds and targets of PMT in treating IS. The databases CTD, DrugBank, DisGeNET, GeneCards, OMIM, TTD, PGKB, NCBI, TCMIP, CNKI, PubMed, ZINC, STITCH, BATMAN, ETCM and Swiss provided information on targets related to IS and components of PMT, along with their associated targets. We constructed "compound-target" and protein-protein interaction (PPI) networks sourced from the STRING database using the Cytoscape software. Gene Ontology (GO) enrichment analysis and KEGG pathway analysis were conducted using the DAVID database. Molecular docking between core targets and active compounds was conducted using Autodock4 software. Experiments were performed in an oxygen-glucose deprivation and reperfusion (OGD/R) model to validate the anti-IS activity of compounds isolated from PMT preliminarily. Network pharmacological analysis revealed 16 core compounds, including resveratrol, polydatin, TSG, ω- hydroxyemodin, emodin anthrone, tricin, moupinamide, and others, along with 11 high-degree targets, such as PTGS1, PTGS2, ADORA1, ADORA2, CA1, EGFR, ESR1, ESR2, SRC, MMP3 and MMP9. GO and KEGG enrichment analyses revealed the involvement of HIF-1, Akt signaling pathway and energy metabolism-related signaling pathways. Molecular docking results emphasized eight key compounds and confirmed their interactions with corresponding targets. In vitro OGD/R model experiments identified TSG and tricin as the primary active substances within PMT for its anti-stroke activity. This study contributes new insights into the potential development of PMT for stroke prevention and treatment.
ABSTRACT
Waste-activated sludge (WAS) is regarded as a source of hazardous waste pollution from sewage treatment plants. To efficiently deal with WAS, vortex cavitation circulating fluidised grinding technology (VCCFGT) was proposed as a novel circulating fluidisation technology (CFT) to disintegrate WAS. To be specific, we investigated the effects of disintegration duration, pressure, and filling ratio of mill balls on sludge disintegration. The results of chemical and physical evaluation showed that the values of soluble chemical oxygen demand (SCOD), disintegration degree (DDSCOD), DNA, protein, carbohydrate, and NH4+-N increased with the increase in the filling ratio of the mill balls. Under a pressure and filling ratio of 0.30 MPa and 1.6%, respectively, the maximum effect was achieved after 60 min of treatment. Compared to those in the treatment without mill balls, the values of SCOD, DDSCOD, DNA, protein, carbohydrate, and NH4+-N in the treatment using mill balls increased by 218, 229, 230, 177, 371, and 190%, respectively. As a result of this technology, the temperature of the sludge dramatically increased, rising approximately 42.9 °C. Compared to that of the raw sludge, the sludge particle size after treatment was reduced by 83.25% at most, and the morphology of the sludge comprised smaller flocs. Compared to that of the ball-milling method, the mill balls filling ratio of VCCFGT reduced by 93.60-98.12%. Compared to that of sludge disintegration by the vortex cavitation method, VCCFGT indicating good disintegration degree (increased by 229%) and economic feasibility. VCCFGT has good application prospects for sludge disintegration. The main mechanisms of sludge disintegration and organic release include centrifugal force, grinding, shear force, cavitation, and cyclic fatigue effects, among which grinding plays a leading role. This study concluded that CFT can effectively disintegrate sludge flocs and disrupt bacterial cell walls.
