Exploring GC–MS‐Based Phytochemistry and Network Pharmacology to Elucidate the Multi‐Target Therapeutic Potential of Betel Leaf Oil as an Analgesic and Anti‐Inflammatory Agent

Betel leaf (Piper betle L.) has been widely used in traditional medicine for treating pain, inflammation, and microbial infections due to its rich phytochemical content. However, the molecular mechanisms underlying its analgesic and anti-inflammatory effects remain incompletely understood. This study aimed to analyze the phytochemical composition of betel leaf oil using GC-MS and to explore its therapeutic mechanisms through network pharmacology targeting genes involved in pain and inflammation pathways. Betel leaf essential oil was extracted and analyzed with GC-MS to identify bioactive metabolites. The identified compounds were further examined using network pharmacology to predict target genes and develop compound-protein interaction networks. Gene ontology enrichment, DisGeNET disease enrichment, and gene-disease association analyses were conducted to investigate biological pathways and disease relevance. The GC-MS analysis revealed bioactive compounds including estragole, oleic acid, chavicol acetate, and eugenol, interacting strongly with genes such as SCN9A, SCN10A, TRPV1, ICAM1, STAT3, TNF, and BDNF involved in pain and inflammatory responses. The findings suggest that the bioactive components of betel leaf oil may possess analgesic and anti-inflammatory properties, indicating its potential as a source of therapeutic agents. Molecular docking further demonstrated favorable binding of eugenol and oleic acid with TNF-α and TRPV1, supporting their potential anti-inflammatory and analgesic activities. These integrated findings suggest that the bioactive constituents of betel leaf oil possess potential analgesic and anti-inflammatory activities through multi-target interactions, although further experimental validation is required.