In the theory of traditional Chinese medicine (TCM), the use of botanical drugs emphasizes the symptom characteristics of the population. Data from randomized controlled trials show that lowering blood pressure while inhibiting the renin-angiotensin-aldosterone system (RAAS) yields additional benefits for patients with urinary albumin/creatinine ratios greater than 33.9 mg/mmol ( Bakris et al., 2010 Schmieder et al., 2011).īotanical drugs have advantages in improving HN symptoms. Patients typically first present with microalbuminuria and glomerular ischemia aggravated to decompensation, followed by albuminuria, elevated serum creatinine levels, polyuria, increased nocturia, and other symptoms ( Bakris, 2004 Ibsen et al., 2005 Hart and Bakris, 2010). Long-term hypertension leads to renal arteriosclerosis, transparent changes in glomerular arterioles, increased renal vascular resistance, inflammatory reactions, and renal tubulointerstitial fibrosis ( Seccia et al., 2017). Glomerulosclerosis is the most common renal pathological change caused by hypertension. According to the current guidelines ( Hart and Bakris, 2010 Ene-Iordache et al., 2016 Carey et al., 2018 Williams et al., 2018), patients with HN should not only manage their blood pressure but should also consider renal protection to obtain long-term benefits. Hypertensive nephropathy (HN) is one of the common complications of hypertension and can significantly increase the prevalence of chronic kidney disease (CKD) ( Ene-Iordache et al., 2016 Williams et al., 2018). 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. With respect to target and pathway enrichment, Gao Shen Formula acts on inflammatory factors such as TNF-α, IL-1β, and IL-6 and regulates the NF-κB signaling pathway and downstream glucose and lipid metabolic pathways.Ĭonclusion: 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. 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. 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. Results: A total of 14 botanical drugs and five symptom communities were obtained from real-world clinical data. Animal experiments were performed at the target and pathway levels to analyze the mechanism. The clinical efficacy of botanical drugs was verified by a retrospective cohort. Hierarchical clustering was used to screen for effective botanical drugs. The K-nearest neighbors (KNN) model was used to analyze the clinical and biological characteristics of botanical drug compounds to determine the effective compounds. 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 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. However, botanical drug prescriptions have not been summarized. Traditional Chinese medicine has long been used in the clinical treatment of Hypertensive nephropathy.
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