Computational and Experimental Evaluation of Alkaloid Compounds from Papaver somniferum as Dual COX-2 and TNF-α Inhibitors

Poyizar Poyizar; Nurfitriyana Rahmat; Syaiful Katadi; Rahayu Aprianti; Irman Idrus

doi:10.37899/journallamedihealtico.v7i1.3065

Poyizar Department of Pharmacy, STIKES Pelita Ibu, Kendari City, Southeast Sulawesi, Indonesia
Nurfitriyana Rahmat Department of Pharmacy, STIKES Pelita Ibu, Kendari City, Southeast Sulawesi, Indonesia
Syaiful Katadi Department of Pharmacy, STIKES Pelita Ibu, Kendari City, Southeast Sulawesi, Indonesia
Rahayu Aprianti Department of Pharmacy, STIKES Pelita Ibu, Kendari City, Southeast Sulawesi, Indonesia
Irman Idrus Department of Pharmacy, STIKES Pelita Ibu, Kendari City, Southeast Sulawesi, Indonesia

DOI: https://doi.org/10.37899/journallamedihealtico.v7i1.3065

Keywords: Alkaloids, Papaver Somniferum, Dual COX-2 and TNF-α, Inhibitors, Computational Study, Experimental Assay

Abstract

This study aimed to evaluate the computational and experimental potential of alkaloid compounds isolated from Papaver somniferum as dual inhibitors of cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) in an in vitro inflammatory model. The alkaloid fraction was purified from dried capsules/latex of Papaver somniferum and subsequently tested using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Anti-inflammatory activity was assessed by measuring reductions in prostaglandin E₂ (PGE₂) production as an indicator of COX-2 inhibition and TNF-α levels in the cell culture supernatant. Preliminary safety evaluation was conducted using an MTT cytotoxicity assay on non-tumor cells, along with analysis of COX-2 and TNF-α gene expression using RT-qPCR. The alkaloid fraction exhibited concentration-dependent inhibitory effects on both PGE₂ and TNF-α production, with IC₅₀ values observed within the intermediate concentration range. In contrast, the CC₅₀ value in non-tumor cells was substantially higher, resulting in a favorable selectivity index that suggests a relatively wide therapeutic window. Furthermore, treatment with non-toxic concentrations of the alkaloid fraction led to a significant downregulation of COX-2 and TNF-α mRNA expression, supporting the hypothesis that its anti-inflammatory mechanism involves modulation of pro-inflammatory transcriptional pathways. Overall, the alkaloid fraction derived from Papaver somniferum demonstrates promising potential as a multitarget anti-inflammatory agent and warrants further investigation as a source of lead compounds or phytopharmaceutical candidates for the treatment of chronic inflammatory diseases.

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