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Quantum, docking, and in vitro studies were performed to evaluate the immunomodulatory function of two lignans isolated from Artemisia cina —3-demethoxy-6-O-demethylisoguaiacin ( L1 ) and norisoguaiacin ( L2 )—through individual molecular docking with cyclooxygenase-2 (COX-2) and their mixture for cytokine assays. The structures of L1 and L2 were optimized using density functional theory with the B3LYP/6–311++G(d,p) method. The optimized structures were then docked into the COX-2 active site, revealing slightly lower binding affinities (ΔG = −7.57 and −7.13 kcal/mol, respectively) compared with naproxen (−8.95 kcal/mol). The interactions of the ligands with Ser530 and Arg120 in the arachidonate-binding site predict a potential COX-2 inhibition through π-donor hydrogen interactions, along with several hydrophobic and π–π interactions. In the in vitro assays, both lignans significantly upregulated the anti-inflammatory cytokines interleukin (IL)-6, IL-4, and IL-13, which are involved in host protection against nematodes. By contrast, the chemokine CXCL8 was downregulated, indicating a reduction in inflammatory signaling. Moreover, the combination of L1 and L2 with lipopolysaccharide showed a synergistic effect, increasing the relative expression of IL-13 (212.8-fold), highlighting their immunomodulatory activity. These findings from in silico and in vitro assays suggest that the lignans could have potential anti-inflammatory effects, but direct evidence of COX-2 enzymatic inhibition is still lacking. Further in vivo studies are warranted to validate their therapeutic potential. Further in vivo studies are warranted to validate their therapeutic potential.
Flores et al. (Thu,) studied this question.