Mechanism of Folium Polygoni Cuspidati in liver-yang-hyperactivity hypertension based on network pharmacology,molecular docking and experimental pharmacological validation

At present,the global form of hypertension is severe,and liver-yang-hyperactivity hypertension(GYSK hypertension)is the most common type of hypertension.Folium Polygoni Cuspidati(HZY)are mainly used in Yunnan,China,to treat dizziness,headache,and hypertension caused by GYSK,and the content of the active ingredients of HZY and its efficacy varies in different periods.However,the mechanism of action and the effect of harvesting period are not clear. The purpose of this research was to investigate the effect of HZY in April and September on GYSK hypertension. The model of GYSK hypertension was established with aconite decoction and L-NAME,and the blood pressure,the symptoms of GYSK,the cardiac index and the pathological changes of aorta were observed,to study the effect of HZY in April and September on GYSK hypertension.The chemical composition of HZY was analysed by UPLC-QTOF-MS and its mechanism for the treatment of GYSK hypertension was predicted by network pharmacological studies and experimentally validated using serum metabolomics and western blot techniques. April HZY and September HZY can significantly improve the GYSK symptoms of rats,inhibit the RAAS system,improve oxidative stress and regulate blood lipids so as to play a blood pressure lowering efficacy and have a protective effect on the vascular endothelial cells.UPLC-QTOF-MS yielded 29 components of HZY,and network pharmacology predicted that its mechanism may be related to Lipid and atherosclerosis,PI3K/Akt signaling pathway,MAPK signaling pathway and TNF signaling pathway,etc.Western Blot validation showed that HZY activated PI3K,p-Akt protein expression and inhibited p-erk,p-p38 and TNF-α protein expression.Serum metabolomics suggested that April HZY exerts its efficacy mainly by regulating amino acid metabolism and September HZY mainly by regulating lipid metabolism. In GYSK hypertensive rats treated for three weeks,both April HZY and September HZY could have antihypertensive effects,but the mechanisms of action were different and similar,both could regulate metabolite disorders of sugars,lipids,aminoacids and peptides,and regulate blood pressure through the PI3K/Akt-eNOS and MAPK signalling pathways,with the difference that April HZY had stronger regulatory effects on the metabolism of amino acids.metabolism.