Integrated proteomic and metabolomic analysis reveals the potential therapeutic mechanism of Quanduzhong capsule in rats with spontaneous hypertension and knee osteoarthritis.
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引用次数: 0
Abstract
Ethnopharmacological relevance: Quanduzhong capsule (QDZ), derived from Eucommia ulmoides Oliv., has been traditionally used in Chinese medicine for its beneficial effects on musculoskeletal health. Its clinical application has extended to conditions such as spontaneous hypertension combined with knee osteoarthritis (SKOA). However, the specific mechanisms by which QDZ alleviates symptoms and improves outcomes in this complex condition remain to be fully elucidated.
Aim of the study: This study aims to evaluate the therapeutic potential of QDZ in treating SKOA. By performing serum proteomics and metabolomics, we seek to explore the related biological pathways and elucidate the mechanisms underlying QDZ's effects on SKOA.
Materials and methods: Serum samples from control, spontaneous hypertension (SHR), SKOA, and SKOA treated with QDZ groups were analyzed using data-independent acquisition-based proteomics to identify differentially expressed proteins. Serum levels of angiotensin II, norepinephrine, endothelin-1, classical pro-inflammatory factors such as macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-1 beta were measured. Additionally, serum metabolomics was performed to examine the changes in metabolite profiles. Correlation analysis was conducted to link changed proteins and metabolites with key pathways affected by QDZ.
Results: Proteomics analysis revealed significant alterations in serum protein expression between control, SHR, and SKOA groups, with changes in pathways related to immune regulation and vascular function. KEGG enrichment analysis highlighted pathways such as endocytosis, synaptic vesicle cycling, and immune responses were enriched in SKOA group compared with control group. QDZ treatment significantly modulated above pathways and reduced inflammatory and cardiovascular markers which were upregulated in SKOA group. Metabolomics analysis showed that QDZ reversed SKOA-induced changes in amino acid and organic acid metabolism, affecting pathways including valine, leucine, and isoleucine metabolism, as well as the TCA cycle. Correlation analysis revealed significant relationships between key proteins and metabolites, underscoring the integrated role of immune and metabolic pathways in QDZ's effects.
Conclusions: Our results indicate QDZ has a significant therapeutic potential for SKOA by modulating both protein and metabolite profiles associated with inflammation, vascular dysfunction, and metabolic imbalance. Our findings provide insights into the mechanisms through which QDZ exerts its effects and support its use as a promising treatment for SKOA. This study highlights the impact of QDZ on proteomic and metabolomic alterations, offering a basis for its broader application in treating SKOA.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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