Integrating Metabolomics LC-HRMS, and Network Pharmacology of Garcinia forbesii King Leaf Extract, Potential for Treatment of Renal Ischemic Reperfusion Injury
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Abstract
Garcinia forbesii King, locally known as Mundar in South Kalimantan, is rich in xanthone natural compounds recognized for their strong antioxidant and anti-inflammatory activities, which are thought to protect the kidneys from damage. However, the exact biological pathways are not fully understood. This study aimed to identify the bioactive compounds in Garcinia forbesii leaf and explore their potential mechanisms in protecting against kidney injury using a network pharmacology approach. The compounds were detected through liquid chromatography– high resolution mass spectrometry (LC-HRMS), and their chemical structures were represented in SMILES format using PubChem. Drug-likeness properties were assessed using ADMETLab, while potential target genes were identified through the Comparative Toxicogenomics Database and the Similarity Ensemble Approach (SEA). Genes relevant to renal ischemia–reperfusion injury (RIRI) were obtained from GeneCards. The predicted protein targets were then analyzed to determine their associated pathways and functions, and compound–target interaction networks were visualized with Cytoscape 3.10.2. Out of 219 bioactive compounds, 25 showed favorable drug-like properties. The key gene targets identified included TP53, TNF, BCL2, JUN, IL6, RELA, CASP3, IRS1, GSK3B, and NFE2L2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the extract primarily influences processes related to apoptosis, gene regulation, and inflammation. The predicted protein targets were largely localized in the cytosol, exosomes, and cytoplasm, suggesting potential modulation of protein–protein interactions. These results point to possible mechanisms by which Garcinia forbesii may protect against kidney injury, strengthening its potential as a nephroprotective candidate.
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