HPLC/MS Phytochemical Profiling with Antioxidant Activities of <i>Echium humile</i> Desf. Extracts: ADMET Prediction and Computational Study Targeting Human Peroxiredoxin 5 Receptor

Plant-based antioxidants such as polyphenols have gained significance in primary health care needs, due to their potential and therapeutic use in modern medicine. Thus, the present study aimed to evaluate, for the first time, the effect of solvents on extraction yield, polyphenolics, phytoconstituents and antioxidant properties of various extracts (aqueous, methanol, ethyl acetate, dichloromethane, hexane) of <i>Echium humile</i> Desf. (<i>E</i>. <i>humile</i> Desf.) through in vitro and in silico studies. Statistically, among the various solvents, both methanol (443.05 ± 0.50 mg GAE/g extract) and aqueous (440.59 ± 0.50 mg GAE/g extract) extracts displayed equipotent and highest total phenolics content (TPC), while dichloromethane extract had the maximum total flavonoid content (TFC) (151.69 ± 0.60 mg QE/g extract), total flavonol content (TFlC) (97.39 ± 0.19 mg QE/g extract) and total carotenoids content (TCC) (537.85 ± 5.06 mg <i>β</i>-CE/g). Meanwhile, the highest total condensed tannin content (TCTC) was recorded together with hexane (131.50 ± 0.1 mg GAE/g extract) and dichloromethane (125.74 ± 5.72 GAE/g extract) extracts. The results of antioxidant studies revealed that ethyl acetate extract exhibited a potent scavenging effect through 2,2-diphenyl-1-picrylhydrazyl radical (DPPH^•) (IC₅₀ = 17.25 ± 1.76 µg/mL) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS^•+) (1433.30 ± 1.78 µg/mL), while dichloromethane extract displayed significant (<i>p</i> < 0.05) ferric ion reducing antioxidant power (FRAP) activity (375.00 ± 0.02 µg/mL) and total antioxidant capacity (TAC) (1999.00 ± 2.05 µg AAE/g). In addition, the quantification of the polyphenolics content of the most active <i>E. humile</i> Desf. extract, ethyl acetate has been assessed by HPLC/MS, leading to the identification of <i>p</i>-coumaric, <i>trans</i>-ferulic acids and cirsiliol as major constituents. Additionally, molecular docking analysis showed that among the selected phytocompounds, naringin (−7.0 kcal/mol) followed by 1,3-di-<i>O</i>-caffeoyquinic acid (−6.6 kcal/mol), rosmarinic acid (−6.6 kcal/mol), rutin (−6.5 kcal/mol) and apigenin-7-<i>O</i>-glucoside (−6.5 kcal/mol) showed the lowest binding potential. Furthermore, ADME and toxicity parameters justify that identified compounds from ethyl acetate extract are safer to replace the synthetic drugs with side effects. The obtained results can provide valuable information on the medical and therapeutic potential use of <i>E. humile</i> Desf. as a potent antioxidant agent to improve immunity.