Background: The long-term use of conventional anti-inflammatory drugs is associated with significant adverse effects, necessitating the search for safer alternatives from natural sources. The genus Clerodendrum is widely used in traditional medicine, but the specific anti-inflammatory potential of Clerodendrum thomsoniae Balf.f. remains underexplored. This study aimed to identify the major phytochemicals in an alcoholic leaf extract of C. thomsoniae and evaluate their potential as Cyclooxygenase-2 (COX-2) inhibitors using a computational approach.

Methods: An alcoholic extract of C. thomsoniae leaves was prepared and subjected to Gas Chromatography-Mass Spectrometry (GC-MS) for phytochemical profiling. The major identified compounds were then evaluated for their anti-inflammatory potential via molecular docking studies against the COX-2 enzyme using PyRx software. Rofecoxib was used as a standard reference drug. Furthermore, the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of the top-performing compounds were predicted using the SwissADME online server to assess their drug-likeness.

Results: The GC-MS analysis successfully identified 15 distinct phytochemicals in the extract, with Verbenone, Linalool, and Eucalyptol being the most abundant. The molecular docking results revealed that Verbenone exhibited the highest binding affinity of -8.5 kcal/mol, which was superior to that of the standard drug Rofecoxib (-7.9 kcal/mol). The analysis of the binding pose showed strong hydrogen bond and hydrophobic interactions between Verbenone and the key amino acid residues in the COX-2 active site.

Conclusion: The findings suggest that Clerodendrum thomsoniae is a rich source of bioactive compounds with significant anti-inflammatory potential. Verbenone, identified as the major component, shows great promise as a selective COX-2 inhibitor and warrants further in-vitro and in-vivo validation as a lead compound for developing novel anti-inflammatory therapies.