Exploratory Antinociceptive and Anti-Inflammatory Effects of Dittrichia viscosa Extracts: HPLC-PDA Fingerprinting, Preliminary Acute Tolerability, ADMET Prediction, and Docking-Based Prioritization.

The present exploratory study examined a hydroethanolic extract (HEE) and an ethyl-acetate-derived fraction operationally termed the polyphenolic fraction (PF) of Dittrichia viscosa by combining HPLC-PDA fingerprinting, acute nociception and inflammation models, a 72-h acute oral tolerability screen of HEE, and in silico prioritization. The HPLC-PDA fingerprint of HEE contained 31 peaks. Because the available analytical record did not support validated absolute quantification, platform-exported values are reported only as relative chromatographic abundance. The larger peaks included p-coumaric acid (7.20%), caffeic acid (5.11%), a putative caffeic acid-O-hexoside dimer (4.55%), a putative isorhamnetin-O-hexoside (3.57%), a putative hydroxybenzoic acid hexoside (3.25%), and apigenin (3.23%); six annotations were standard-supported, whereas the remaining assignments were putative. In rats (n = 5/group), every treatment-control comparison in the writhing and formalin models was significant in the summary-statistic Dunnett reanalysis (adjusted p < 0.0001). PF at 100 mg/kg produced 59.5% writhing inhibition and mean differences versus vehicle of -38.46 s (95% CI -40.42 to -36.50) and -23.00 s (95% CI -24.45 to -21.55) in the early and late formalin phases, respectively. In the carrageenan model, significant differences occurred mainly at 6 h; PF at 100 mg/kg differed from vehicle by -0.24 cm (95% CI -0.34 to -0.14; adjusted p = 0.0002). Percentage inhibition values are descriptive. No mortality or overt clinical signs were observed after HEE doses up to 4000 mg/kg during 72 h, which constitutes preliminary acute tolerability evidence for HEE only. Predicted ADMET outputs and AutoDock Vina scores prioritized candidate ligands but do not establish exposure, safety, target inhibition, or causal contribution to the extract-level effects. These exploratory findings support further preclinical investigation, subject to chemical confirmation, raw-data-based longitudinal statistics, direct target assays, and guideline-compliant safety studies.