Essential oils from fruits of Zanthoxylum armatum exhibit antioxidant, anti-inflammatory, and anticancer properties by inhibiting p38-MAPK pathway
Shirani Punniyamoorthy, Achyut Adhikari, Janaki Baral, Gagandeep Singh, Yuba Raj Pokharel
Abstract
Essential oils from Zanthoxylum armatum fruits, known for their therapeutic properties, were extracted from three regions of Nepal: Myagdi (EO1), Surkhet (EO2), and Salyan (EO3). GC–MS analysis identified linalool as the predominant compound (58.31 %, 58.45 %, and 80.37 % in EO1, EO2, and EO3, respectively), along with limonene and trans -methyl cinnamate. These oils exhibited strong antioxidant activity as assessed by ferric reducing power, phosphomolybdenum capacity, and NO scavenging along with anti-inflammatory effects by reducing albumin denaturation and NO production in LPS-induced RAW 264.7 cells. Cytotoxicity assays showed dose-dependent effects against lung (NCI-H460), skin (A431), and prostate (PC3) cancer cells, with the highest activity in NCI-H460 (IC 50 = 78.5 μg/mL). Mechanistic studies revealed reduced clonogenicity, inhibited migration, S-phase cell cycle arrest, and apoptosis via downregulation of RACK1, p38 MAPK, c-MYC, Vimentin, and Bcl-2. In silico docking confirmed strong interactions of linalool and limonene with p38 MAPK and c-MYC, respectively. These results highlight the potential of Z. armatum essential oils for antioxidant, anti-inflammatory, and anticancer applications.