Interaction of <i>Inula viscosa</i> (L.) Aiton with Iba1 via Rosmarinic Acid and Rutin: Insights from Computational Models and Biological Effects

Abstract Inula viscosa (L.) Aiton is a traditional medicinal plant extensively utilized in Mediterranean nations for the treatment of rheumatic pain, inflammatory disorders, diabetes, anemia, and cancer. This study further explored its anti‐inflammatory mechanisms through the highest components, chlorogenic acid, rosmarinic acid, and rutin, on the expression of the ionized calcium‐binding adapter molecule 1 (Iba1) on monocyte‐derived macrophage‐like cells. Iba1 is known to contribute pathogenesis of diverse inflammatory diseases. HPLC analysis identified 13 major phenolic compounds, with rosmarinic acid, chlorogenic acid, and rutin as major components. The aqueous extract of the plant and its major components exhibited dose‐dependent antiproliferative activity on pTHP‐1, RAW264.7, and PCS‐201–012 cells. Immunofluorescence staining revealed a significant reduction in Iba1 protein expression, which is associated with inflammation, at the high dose of I. viscosa and rutin. Molecular docking studies indicated that rosmarinic acid and rutin had the strongest predicted interactions with Iba1, with docking scores of −12.403 and −12.301 kcal/mol and MM/GBSA binding energies of −64.47 and −84.20 kcal/mol, respectively. I. visoca and its major components were observed to significantly suppress iNOS activity in LPS‐stimulated cells; these findings were also supported by RT‐PCR results. Treatment with the high dose of I. viscosa resulted in 9.45% necrotic cells and caused cell cycle arrest in the S phase (59.2 ± 5.23%). This suggests that it may potentially reduce the proliferation of activated macrophages. In the fibroblast migration assays, the relative wound closure rate was found to be significant 27.06 ± 18.09% at the low dose of I. viscosa and 31.59 ± 22.42% at the high dose of I. viscosa . Although the relatively low wound closure rate limits tissue repair, it may benefit chronic wounds and fibrosis by suppressing excessive cell proliferation and inflammation. These results suggest that I. viscosa is a promising natural source of bioactive compounds with potential applications in anti‐inflammatory drug development.