Anti-Inflammatory Properties of Agarwood (Aquilaria Spp.): An Integrated Review of Phytochemistry, Molecular Mechanisms, and Therapeutic Applications

Abstract: Agarwood, the aromatic resinous heartwood derived from Aquilaria and Gyrinops species, represents a promising natural resource for anti-inflammatory drug development. This comprehensive review synthesizes current scientific understanding of agarwood’s anti-inflammatory properties, bridging traditional medicinal applications with modern pharmacological validation. The review examines the phytochemical foundations of bioactivity, focusing on sesquiterpenoids and 2-(2-phenylethyl) chromones (PECs) as principal bioactive constituents. We elucidate multi-target molecular mechanisms through which these compounds modulate inflammatory responses, primarily via inhibition of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, along with emerging targets including the NLRP3 inflammasome. Comprehensive analysis of preclinical evidence from both in vitro and in vivo models demonstrates agarwood’s efficacy across diverse inflammatory conditions, including gastrointestinal, hepatic, and neurological inflammation. Critical factors influencing therapeutic application, including phytochemical variability and bioavailability challenges addressed through advanced drug delivery systems, are systematically examined. Despite compelling preclinical data, significant translational gaps exist due to the absence of human clinical trials. This review identifies major challenges in standardization, sustainability, and clinical validation while proposing future research directions to advance agarwood-based therapeutics from traditional remedies to evidence-based medicine. Keywords: agarwood, anti-inflammatory, phytochemistry, molecular mechanisms, NF-κB pathway, 2-(2-phenylethyl) chromones