Integrating network pharmacology, transcriptomics, molecular docking and in vitro experiments to investigate the material basis and mechanism of Liuwei Dihuang Pills for treating diabetic nephropathy.
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Abstract
Background: Diabetic nephropathy (DN) is a common microvascular complication of diabetes. Liuwei Dihuang Pills (LW) has significant clinical efficacy in the treatment of DN, but its pharmacological mechanism and material basis remain poorly understood.
Objective: This study aimed to explore the substance basis and mechanism of action of LW in treating DN.
Design: The potential mechanism of LW was investigated through UPLC/LTQ-Orbitrap-MS and network pharmacology. The activity of LW and its constituent herbs was evaluated in human renal glomerular endothelial cells (HRGEC) and HK2 cells. Key pathways and targets were identified by transcriptomics and validated by qRT-PCR. Molecular docking was employed to screen for active ingredients of LW.
Results: The results showed that LW, Cornus Officinalis (CO), Moutan Cortex (MC), Rhizoma Dioscoreae (RD), and Alismatis Rhizoma (AR) mitigated oxidative damage in HRGEC cells. LW primarily targeted VEGFA and EGR1, thereby modulating the AGE-RAGE signaling pathway in diabetic complications. LW also reduced fibrosis in HK2 cells by up-regulating BMP4 and modulating the TGF-beta signaling pathway. Rehmanniae Radix Praeparata (RRP), CO, MC, RD, and Poria Cocos (PC) were identified as key contributors to improving renal fibrosis. Additionally, 43 potential active ingredients were identified in LW, 13 of which exhibited favorable ADMET properties. Six key ingredients, including taxifolin, cianidanol, gallic acid, caffeic acid, 5-hydroxymethylfurfural, and paeonol were found to be primarily responsible for the effects of LW on microvascular endothelial injury and renal fibrosis.
Conclusion: In summary, these findings reveal the material basis and mechanism of LW against DN, providing a foundation for its clinical application.
期刊介绍：
Food & Nutrition Research is a peer-reviewed journal that presents the latest scientific research in various fields focusing on human nutrition. The journal publishes both quantitative and qualitative research papers.
Through an Open Access publishing model, Food & Nutrition Research opens an important forum for researchers from academic and private arenas to exchange the latest results from research on human nutrition in a broad sense, both original papers and reviews, including:
* Associations and effects of foods and nutrients on health
* Dietary patterns and health
* Molecular nutrition
* Health claims on foods
* Nutrition and cognitive functions
* Nutritional effects of food composition and processing
* Nutrition in developing countries
* Animal and in vitro models with clear relevance for human nutrition
* Nutrition and the Environment
* Food and Nutrition Education
* Nutrition and Economics
Research papers on food chemistry (focus on chemical composition and analysis of foods) are generally not considered eligible, unless the results have a clear impact on human nutrition.
The journal focuses on the different aspects of nutrition for people involved in nutrition research such as Dentists, Dieticians, Medical doctors, Nutritionists, Teachers, Journalists and Manufacturers in the food and pharmaceutical industries.
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