Abstract

Chronic inflammatory diseases are a major global health problem. This study was conducted to evaluate the anti-inflammatory activity of kaffir lime peel essential oil (Citrus hystrix DC.) obtained using Microwave-Assisted Extraction with a network pharmacology approach and in vivo tests using Wistar rats. Identification of compounds in the essential oil was carried out by Gas Chromatography–Mass Spectrometry analysis, which obtained 60 identified compounds such as (−)-citronellal, β-pinene, D-limonene, and linalool. Network pharmacology analysis identified 265 inflammation-related targets, with TP53, IL6, and MAPK3 identified as hub genes. Functional enrichment analysis showed significant involvement in cytokine-cytokine receptor interactions and chemokine signaling pathways. In vivo experiments showed that oral kaffir lime peel essential oil administration (50–400 mg/kgBW) significantly reduced carrageenan-induced paw swelling in Wistar rats compared to negative controls (p < 0.05). Even higher doses (200 and 400 mg/kgBW) produced effects nearly comparable to those of diclofenac sodium (2.25 mg/kgBW). Neutrophil infiltration decreased, while immunohistochemical analysis confirmed decreased TNF -α and IL-6 expression, particularly at the higher doses. These findings suggest that kaffir lime peel essential oil has promising anti-inflammatory activity as a natural alternative to conventional anti-inflammatory drugs.

Key words: anti-inflammatory, Citrus, essential oil, kaffir lime peel, phytochemical, GC-MS