RESUMO
Background/aim: Hypertensive nephropathy (HN) is a common complication of hypertension. Traditional Chinese medicine has long been used in the clinical treatment of Hypertensive nephropathy. However, botanical drug prescriptions have not been summarized. The purpose of this study is to develop a prescription for improving hypertensive nephropathy, explore the evidence related to clinical application of the prescription, and verify its molecular mechanism of action. Methods: In this study, based on the electronic medical record data on Hypertensive nephropathy, the core botanical drugs and patients' symptoms were mined using the hierarchical network extraction and fast unfolding algorithm, and the protein interaction network between botanical drugs and Hypertensive nephropathy was established. The K-nearest neighbors (KNN) model was used to analyze the clinical and biological characteristics of botanical drug compounds to determine the effective compounds. Hierarchical clustering was used to screen for effective botanical drugs. The clinical efficacy of botanical drugs was verified by a retrospective cohort. Animal experiments were performed at the target and pathway levels to analyze the mechanism. Results: A total of 14 botanical drugs and five symptom communities were obtained from real-world clinical data. In total, 76 effective compounds were obtained using the K-nearest neighbors model, and seven botanical drugs were identified as Gao Shen Formula by hierarchical clustering. Compared with the classical model, the Area under the curve (AUC) value of the K-nearest neighbors model was the best; retrospective cohort verification showed that Gao Shen Formula reduced serum creatinine levels and Chronic kidney disease (CKD) stage [OR = 2.561, 95% CI (1.025-6.406), p < 0.05]. With respect to target and pathway enrichment, Gao Shen Formula acts on inflammatory factors such as TNF-α, IL-1ß, and IL-6 and regulates the NF-κB signaling pathway and downstream glucose and lipid metabolic pathways. Conclusion: In the retrospective cohort, we observed that the clinical application of Gao Shen Formula alleviates the decrease in renal function in patients with hypertensive nephropathy. It is speculated that Gao Shen Formula acts by reducing inflammatory reactions, inhibiting renal damage caused by excessive activation of the renin-angiotensin-aldosterone system, and regulating energy metabolism.
RESUMO
Hypertension and coronary heart disease are the most common cardiovascular diseases, and traditional Chinese medicine is applied as an auxiliary treatment for common cardiovascular diseases. This study is based on 3 years of electronic medical record data from the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. A complex network and machine learning algorithm were used to establish a screening model of coupled herbs for the treatment of hypertension complicated with coronary heart disease. A total of 5688 electronic medical records were collected to establish the prescription network and symptom database. The hierarchical network extraction algorithm was used to obtain core herbs. Biological features of herbs were collected from public databases. At the same time, five supervised machine learning models were established based on the biological features of the coupled herbs. Finally, the K-nearest neighbor model was established as a screening model with an AUROC of 91.0%. Seventy coupled herbs for adjuvant treatment of hypertension complicated with coronary heart disease were obtained. It was found that the coupled herbs achieved the purpose of adjuvant therapy mainly by interfering with cytokines and regulating inflammatory and metabolic pathways. These results show that this model can integrate the molecular biological characteristics of herbs, preliminarily screen combinations of herbs, and provide ideas for explaining the value in clinical applications.