Discovering the Anti-Inflammatory Potential of Compounds Isolated from the Aerial Parts of Gelasia tomentosa (L.) Zaika, Sukhor. & N.Kilian (Syn. Scorzonera tomentosa), Through In Vitro Techniques and Advanced In Silico Modeling Approaches

<i>Gelasia tomentosa</i> (L.) Zaika, Sukhor. & N.Kilian which is known formerly as <i>Scorzonera tomentosa</i> L., a wild edible plant species in Turkey, is traditionally used against rheumatism and for wound healing. In this study, we explore its anti-inflammatory compounds, evaluating effectiveness through human red blood cell stabilization and in silico models, alongside physico-chemical and pharmacokinetic profiles. In vitro activity-guided fractionation allowed the isolation of sixteen compounds from the aerial parts of <i>G. tomentosa</i>, which were identified as hyperoside (<b>1</b>), isoquercetin (<b>2</b>), quercetin 3-<i>O</i>-<i>β</i>-apiofuranosyl-(1→2)-<i>β</i>-galactopyranoside (<b>3</b>), quercetin 3-<i>O</i>-<i>β</i>-apiofuranosyl-(1→2)-<i>β</i>-glucopyranoside (<b>4</b>), 7-methoxyapigenin-6-<i>C</i>-<i>β</i>-apiofuranosyl-(1→2)-<i>β</i>-glucopyranoside (<b>5</b>), apigenin-6-<i>C</i>-<i>β</i>-apiofuranosyl-(1→2)-<i>β</i>-glucopyranoside (<b>6</b>), dihydrodehydrodiconiferyl-alcohol-4-<i>O</i>-<i>β</i>-glucopyranoside (<b>7</b>), cichoriin (<b>8</b>), 7-<i>O</i>-methylisoorientin (<b>9</b>), isoorientin (<b>10</b>), swertisin (<b>11</b>), 3,5-<i>O</i>-dicaffeoylquinic acid methyl ester (<b>12</b>), 4,5-<i>O</i>-dicaffeoylquinic acid methyl ester (<b>13</b>), staphylinioside E (<b>14</b>), 3,5-<i>O</i>-dicaffeoylquinic acid (<b>15</b>), and 4,5-<i>O</i>-dicaffeoylquinic acid (<b>16</b>). Compound 16 displayed the highest potential anti-inflammatory activity (IC₅₀ = 0.55 ± 0.00 mg/mL). However, the fraction with compounds displayed stronger biological activity than the isolated ones. In silico findings supported the anti-inflammatory potential, enhancing TP53 expression and cell membrane protection. Cichoriin (<b>8</b>) and staphylinioside E (<b>14</b>) are in accordance with Lipinski's, Pfizer's, GSK's, and Golden Triangle rules, indicating a favorable ADME profile as a drug candidate. Further studies are needed to test this potential in specific inflammation models.