A Network Pharmacology Approach for Exploring the Mechanisms of Panax notoginseng Saponins in Ischaemic Stroke

Abstract

Background. Panax notoginseng saponins (PNS) have been deemed effective herb compounds for treating ischaemic stroke (IS) and improving the quality of life of IS patients. This study aimed to investigate the underlying mechanisms of PNS in the treatment of IS based on network pharmacology. Methods. PNS were identified from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible targets were predicted using the PharmMapper database. IS-related targets were identified from the GeneCards database, OMIM database, and DisGeNET database. A herb-compound-target-disease network was constructed using Cytoscape, and protein-protein interaction (PPI) networks were established with STRING. GO enrichment and KEGG pathway analysis were performed using DAVID. The binding of the compounds and key targets was validated by molecular docking studies using AutoDock Vina. The neuroprotective effect of TFCJ was substantiated in terms of oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde) and the levels of IGF1/PI3K/Akt pathway proteins. Results. A total of 375 PNS targets and 5111 IS-related targets were identified. Among these targets, 241 were common to PNS, and IS network analysis showed that MAPK1, AKT1, PIK3R1, SRC, MAPK8, EGFR, IGF1, HRAS, RHOA, and HSP90AA1 are key targets of PNS against IS. Furthermore, GO and KEGG enrichment analysis indicated that PNS probably exert therapeutic effects against IS by regulating many pathways, such as the Ras, oestrogen, FoxO, prolactin, Rap1, PI3K-Akt, insulin, PPAR, and thyroid hormone signalling pathways. Molecular docking studies further corroborated the experimental results.The network pharmacology results were further verified by molecular docking and in vivo experiments. Conclusions. The ameliorative effects of PNS against IS were predicted to be associated with the regulation of the IGF1-PI3K-Akt signalling pathway. Ginsenoside Re and ginsenoside Rb1 may play an important role in the treatment of IS.

Nerolidol Attenuates Cerebral Ischemic Injury in Middle Cerebral Artery Occlusion-Induced Rats via Regulation of Inflammation, Apoptosis, and Oxidative Stress Markers

“…34, 35 Cerebral infarct is another predictor of ischemic stroke which occurs due to the intracerebral artery occlusion. 36, 37 Nerolidol treatment in MCAO-performed rats significantly decreased both brain edema and cerebral infarct proving the neuroprotective role against ischemic stroke.…”

To study the mechanism of panax notoginseng in the treatment of aspirin resistance in the secondary prevention of stroke based on TLR4/MyD88/NF-κB signaling pathway: A study protocol

“…Panax notoginseng (Sanqi) powder can be used for cerebral infarction by the effect of activating blood and removing stasis. [23] Its main active components, total saponins of Panax notoginseng (Sanqi), can effectively reduce blood lipid -glucose content, dilate blood vessels, decompose and inhibit the small thrombi in vessels with the enzyme-promoted cascade reaction, which has a certain effect on stroke. [22] A great deal of experimental evidence indicates that inflammatory injury exerts a significant impact on the development of cerebral ischemia.…”

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

“…We hypothesized that TFCJ might exert its neuroprotective effects by suppressing apoptosis and oxidative stress by activating the PI3K/Akt/mTOR signaling pathway. The important predictors of IS are the neurological deficit scores and cerebral infarction ( Zhang H. et al, 2020 ; Lin et al, 2021 ; Wang et al, 2021 ). In this study, rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h. In the early phase (first few minutes to a few hours) after intracerebral artery occlusion, the infarcted area containing ischemic tissue gradually spreads outwards.…”