Integrated Metabolomics and Network Pharmacology to Establish the Action Mechanism of Qingrekasen Granule for Treating Nephrotic Syndrome

Abstract

Nephrotic syndrome (NS) is a clinical syndrome resulting from abnormal glomerular permeability, mainly manifesting as edema and proteinuria. Qingrekasen granule (QRKSG), a Chinese Uyghur folk medicine, is a single-flavor preparation made from chicory (Cichorium intybus L.), widely used in treating dysuria and edema. Chicory, the main component in QRKSG, effectively treats edema and protects kidneys. However, the active components in QRKSG and its underlying mechanism for treating NS remain unclear. This study explored the specific mechanism and composition of QRKSG on an NS rat model using integrated metabolomics and network pharmacology. First, metabolomics explored the relevant metabolic pathways impacted by QRKSG in the treatment of NS. Secondly, network pharmacology further explored the possible metabolite targets. Afterward, a comprehensive network was constructed using the results from the network pharmacology and metabolomics analysis. Finally, the interactions between the active components and targets were predicted by molecular docking, and the differential expression levels of the target protein were verified by Western blotting. The metabolomics results showed “D-Glutamine and D-glutamate metabolism” and “Alanine, aspartate, and glutamate metabolism” as the main targeted metabolic pathways for treating NS in rats. AKT1, BCL2L1, CASP3, and MTOR were the core QRKSG targets in the treatment of NS. Molecular docking revealed that these core targets have a strong affinity for flavonoids, terpenoids, and phenolic acids. Moreover, the expression levels of p-PI3K, p-AKT1, p-mTOR, and CASP3 in the QRKSG group significantly decreased, while BCL2L1 increased compared to the model group. These findings established the underlying mechanism of QRKSG, such as promoting autophagy and anti-apoptosis through the expression of AKT1, CASP3, BCL2L1, and mTOR to protect podocytes and maintain renal tubular function.

Research Progress on the Homologous Effects of Cichorium glandulosum Boiss. et Huet on Medicine and Food: A Review

“…It is commonly seen clinically in the treatment of hepatitis, nephritis, gastric fever, hyperlipidemia, hyperuric acid, gout and various febrile diseases. 11 Its health care products and preparations are in various forms, such as granules, oral liquid, pills, and capsules. So far, Cichorium glandulosum Boiss.…”

Integrated network pharmacology and metabolomics analyses of the mechanism underlying the efficacy of Ma‐Mu‐Ran Antidiarrheal Capsules against dextran sulfate sodium–induced ulcerative colitis

“…In this study, serum samples were thawed at room temperature, eluted with 600 μL methanol, and incubated in an ice bath for 15 , following established GC/MS research protocols (Duan et al, 2021). The tube was then centrifuged for 10 min and the supernatant was concentrated via centrifugation before being evaporated to dryness.…”

Network Pharmacology and In Vivo Experimental Validation to Uncover the Renoprotective Mechanisms of Fangji Huangqi Decoction on Nephrotic Syndrome

“…Varghese and Majumdar proposed network pharmacology as an initial inherent approach in identifying the repurposing and synergism of drug candidates for NS treatment [ 11 ]. Some previous studies have identified the efficacy and underlying mechanisms of TCMs treating NS via network pharmacology [ 12 , 13 ]. For instance, Yiqi Huoxue Decoction has been found to enhance renal function and alleviate podocyte injury in NS, and the potential mechanisms involved PI3K-AKT and NF- κ B pathways based on network pharmacology [ 12 ].…”

“…For instance, Yiqi Huoxue Decoction has been found to enhance renal function and alleviate podocyte injury in NS, and the potential mechanisms involved PI3K-AKT and NF- κ B pathways based on network pharmacology [ 12 ]. Duan et al established the underlying mechanism of Qingrekasen granule against NS, including promoting autophagy and antiapoptosis through regulating the expression of AKT1, CASP3, BCL2L1, and mTOR to protect podocytes and maintain renal tubular function [ 13 ]. Furthermore, Zhang et al revealed that FHD possesses the antinephrotic syndrome effect in rat nephropathy model; however, the relative underlying mechanisms have not been fully elucidated [ 14 ].…”