Eucommia ulmoides Oliver-Tribulus terrestris L. Drug Pair Regulates Ferroptosis by Mediating the Neurovascular-Related Ligand-Receptor Interaction Pathway- A Potential Drug Pair for Treatment Hypertension and Prevention Ischemic Stroke

Abstract

BackgroundIn this study, we used the network pharmacology approach to explore the potential disease targets of the Eucommia ulmoides Oliver (EUO)-Tribulus terrestris L. (TT) drug pair in the treatment of hypertension-associated neurovascular lesions and IS via the ferroptosis pathway.MethodsWe used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform to search for the key active compounds and targets of the drug pair. Based on the GeneCards database, the relevant targets for the drug pair were obtained. Then, we performed the molecular docking of the screened core active ingredients and proteins using the DAVID database and the R AutoDock Vina software. Based on the GSE22255 dataset, these screened target proteins were used to build random forest (RF) and support vector machine (SVM) models. Finally, a new IS nomogram prediction model was constructed and evaluated.ResultsThere were 36 active compounds in the EUO-TT drug pair. CHRM1, NR3C1, ADRB2, and OPRD1 proteins of the neuroactive ligand-receptor interaction pathway interacted with the proteins related to the ferroptosis pathway. Molecular docking experiments identified 12 active ingredients of the drug pair that may tightly bind to those target proteins. We constructed a visual IS nomogram prediction model using four genes (CHRM1, NR3C1, ADRB2, and OPRD1). The calibration curve, DCA, and clinical impact curves all indicated that the nomogram model is clinically applicable and diagnostically capable. CHRM1, NR3C1, ADRB2, and OPRD1, the target genes of the four effective components of the EUO-TT drug pair, were considered as risk markers for IS.ConclusionsThe active ingredients of EUO-TT drug pair may act on proteins associated with the neuroactive ligand-receptor interaction pathway to regulate ferroptosis in vascular neurons cells, ultimately affecting the onset and progression of hypertension.

Electroacupuncture Treats Myocardial Infarction by Influencing the Regulation of Substance P in the Neurovascular to Modulate PGI2/TXA2 Metabolic Homeostasis via PI3K/AKT Pathway: A Bioinformatics-Based Multiomics and Experimental Study

“…The integration of computational techniques into traditional medicine is necessary for the integration of systems biology into traditional medicine based on a holistic approach [26][27][28][29][30][31][32][33][34][35][36]. In order to analyze the targets and key pathways associated with AMI treated with EA in rat models, data from the Gene Expression Omnibus (GEO) database were retrieved in this study.…”

Eucommia ulmoides bark extract reduces blood pressure and inflammation by regulating the gut microbiota and enriching the Parabacteroides strain in high-salt diet and N(omega)-nitro-L-arginine methyl ester induced mice

“…EU and its extract geniposidic acid also reduced blood pressure and improved renal hemodynamics in Dahl salt-sensitive hypertensive rats ( Ishimitsu et al, 2021 ). Inflammation is involved in the development of hypertension ( Barbaro et al, 2015 ; Zhang et al, 2022 ), while EU can reduce the inflammation. For instance, our study suggests that EU reduces serum IL-6 and IL-17A, and renal IL-17A, which is consistent with previous studies.…”

“…Eucommia ulmoides Oliv. (EU) is a small tree and EU extract is widely used in East Asia ( Wu et al, 2018 ; Ding et al, 2020 ), due to its wide range of pharmacological effects such as anti-hypertension, anti-inflammatory, anti-hyperlipidemia, anti-diabetes, anti-oxidant, and anti-tumor effects ( Shao et al, 2015 ; Zhang et al, 2022 ). In particular, the EU bark has been used for thousands of years in traditional Chinese medicine to improve hypertension ( Li et al, 2020 ).…”

Role of Iron-Related Oxidative Stress and Mitochondrial Dysfunction in Cardiovascular Diseases

“…Eucommia ulmoides Oliver - L. has recently been reported to regulate ferroptosis through the neurovascular-related ligand-receptor interaction pathway and considered to have the potential of treating hypertension and preventing ischemic stroke [ 104 ].…”