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Explore potential immune-related targets of leeches in the treatment of type 2 diabetes based on network pharmacology
1Anhui University of Traditional Chinese Medicine, Hefei, China.
Introduction:
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that poses a significant global health burden due to its profound effects on systemic physiological homeostasis. Without timely intervention, the disease can progress insidiously, leading to multisystem complications such as cardiovascular, renal, and neuropathic pathologies. Consequently, pharmacological intervention becomes crucial in managing the condition. Leeches have been traditionally used in Chinese medicine for their potential to inhibit the progression of T2DM and its associated complications; however, the specific mechanisms underlying their action and target pathways remain poorly understood. The objective of this study was to predict potential therapeutic targets of leeches in the treatment of T2DM.
Methods:
We collected active components and targets associated with leeches from four online databases, while disease-related targets were sourced from the GeneCards and OMIM databases. Following this, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Gene expression data were obtained from the GSE184050 dataset. Important immune cell types were identified through immunoinfiltration analysis in conjunction with single sample enrichment analysis (ssGSEA). Additionally, weighted co-expression network analysis (WGCNA) was utilized to identify significantly associated genes. Finally, we employed LASSO regression, SVM-RFE, XGBoost, and random forest algorithms to further predict potential targets, followed by validation through molecular docking.
Results:
Leeches may influence cellular immunity by modulating immune receptor activity, particularly through the activation of RGS10, CAPS2, and OPA1, thereby impacting the pathology of Type 2 Diabetes Mellitus (T2DM).
Discussion:
However, it is important to note that our results lack experimental validation; therefore, further research is warranted to substantiate these findings.
Insights
Leeches may help manage Type 2 Diabetes Mellitus (T2DM) by affecting cellular immunity. This study identified potential targets like RGS10, CAPS2, and OPA1, but requires experimental validation.
Area of Science:
- Biomedical research
- Pharmacology
- Immunology
Background:
- Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder with significant global health implications.
- T2DM can lead to severe multisystem complications, necessitating effective pharmacological interventions.
- Traditional Chinese medicine utilizes leeches for T2DM management, but underlying mechanisms are unclear.
Purpose of the Study:
- To predict potential therapeutic targets of leeches in the treatment of T2DM.
- To elucidate the molecular pathways through which leeches may exert their effects on T2DM.
Main Methods:
- Collected leeches' active components and targets from databases.
- Sourced T2DM-related targets from GeneCards and OMIM.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.
- Analyzed gene expression data (GSE184050) and identified immune cell types via ssGSEA.
- Utilized Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning algorithms (LASSO, SVM-RFE, XGBoost, random forest) for target prediction.
- Validated targets through molecular docking.
Main Results:
- Identified potential leeches' therapeutic targets for T2DM.
- Leeches may modulate cellular immunity by activating RGS10, CAPS2, and OPA1.
- These modulations could impact the pathological processes of T2DM.
Conclusions:
- The study predicts potential targets for leeches in T2DM treatment.
- Leech-derived compounds may influence T2DM via immune receptor modulation.
- Experimental validation is crucial to confirm these predicted targets and mechanisms.
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