Mechanistic Study of Schisandra chinensis Fruit Mixture Based on Network Pharmacology, Molecular Docking and Experimental Validation to Improve the Inflammatory Response of DKD Through AGEs/RAGE Signaling Pathway

Abstract

Background: Diabetic kidney disease (DKD) is a major cause of end-stage renal disease (ESRD), and inflammation is the main causative mechanism. Schisandra chinensis fruit Mixture (SM) is an herbal formulation that has been used for a long time to treat DKD. However, its pharmacological and molecular mechanisms have not been clearly elucidated. The aim of this study was to investigate the potential mechanisms of SM for the treatment of DKD through network pharmacology, molecular docking and experimental validation. Methods: The chemical components in SM were comprehensively identified and collected using liquid chromatography-tandem mass spectrometry (LC-MS) and database mining. The mechanisms were investigated using a network pharmacology, including obtaining SM-DKD intersection targets, completing protein-protein interactions (PPI) by Cytoscape to obtain key potential targets, and then revealing potential mechanisms of SM for DKD by GO and KEGG pathway enrichment analysis. The important pathways and phenotypes screened by the network analysis were validated experimentally in vivo. Finally, the core active ingredients were screened by molecular docking. Results: A total of 53 active ingredients of SM were retrieved by database and LC-MS, and 143 common targets of DKD and SM were identified; KEGG and PPI showed that SM most likely exerted anti-DKD effects by regulating the expression of AGEs/RAGE signaling pathway-related inflammatory factors. In addition, our experimental validation results showed that SM improved renal function and pathological changes in DKD rats, down-regulated AGEs/RAGE signaling pathway, and further down-regulated the expression of TNF-α, IL-1β, IL-6, and up-regulated IL-10. Molecular docking confirmed the tight binding properties between (+)aristolone, a core component of SM, and key targets. Conclusion:This study reveals that SM improves the inflammatory response of DKD through AGEs/RAGE signaling pathway, thus providing a novel idea for the clinical treatment of DKD.

Mechanism of Huaiqihuang in treatment of diabetic kidney disease based on network pharmacology, molecular docking and in vitro experiment

“…Screening criteria were applied to preliminarily select the drug components, including an oral bioavailability of greater than or equal to 30% and a drug-likeness of greater than or equal to 0.18, based on established pharmacokinetic parameter standards. [ 12 ] The HERB database ( http://herb.ac.cn/ ) was also utilized as a supplementary resource. [ 13 ] The target names were standardized using the UniProt databas ( https://www.uniprot.org/ ), [ 14 ] and gene names were extracted to identify the targets corresponding to the active ingredients of HQH.…”

“…Once the cell confluency reached 60% to 70%, they were treated with various concentrations of HQH. The experimental groups included a blank group (no cells), a control group (treated with drugfree culture medium), and multiple experimental groups with different mass concentrations of HQH (2,4,6,8,10,12, and 14 mg/mL). The intervention lasted for 48 hours, after which 10 µL of CCK-8 solution was added to each well.…”

Mechanism of traditional Chinese medicine in elderly diabetes mellitus and a systematic review of its clinical application

“…Emerging research suggests that TCM and their active compounds can improve diabetic kidney damage by regulating autophagy ( Liu et al, 2023b ). Based on network pharmacology, molecular docking, and experimental validation, a mixture of Schisandra chinensis fruit improved kidney function and pathological changes in DKD rats, possibly by downregulating the AGEs/RAGE signaling pathway, further downregulating the expression of TNF-α, IL-1β, IL-6, upregulating IL-10, among other mechanisms ( Li et al, 2023a ).…”