Solvent-dependent hemolytic activity and phytochemical profiling of Humulus lupulus L. extracts: Integrating antioxidant assays, DFT analysis, and molecular docking.

Abstract

Humulus lupulus L. is a phytochemically rich medicinal plant with antioxidant and pharmacological potential; however, the direct hemolytic effects of extracts obtained using different solvents remain poorly characterized. This study integrated experimental and computational approaches to evaluate the phytochemical composition, antioxidant potential, elemental profile, and hemolytic activity of aqueous, methanolic, ethanolic, and acetone extracts of H. lupulus L. Total phenolic and flavonoid contents, DPPH and ABTS radical-scavenging activities, and IC50 values were determined. Chemical and elemental profiles were characterized using gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma mass spectrometry, respectively. Hemolytic activity was assessed in human erythrocytes, and selected tentatively identified constituents were further investigated by molecular docking and density functional theory. The extraction solvent markedly influenced the chemical composition and biological responses. Methanol yielded the highest phenolic content and strongest ABTS activity (IC50 = 54.25 μg/mL), whereas ethanol showed the highest flavonoid content and the lowest DPPH IC50 value among the extracts (161.0 μg/mL). Despite its pronounced antioxidant activity, the methanol extract consistently produced the greatest hemolytic effect, while aqueous and ethanolic extracts exhibited substantially greater erythrocyte compatibility. GC-MS revealed distinct solvent-dependent chemical profiles, whereas potassium, calcium, and magnesium were the predominant elements. Docking identified 2,3-dihydroxypropyl hexadecanoate as the most consistently interacting constituent, particularly toward hemoglobin, erythrocyte Band 3, and TRPV4. Density functional theory revealed substantial differences in electronic reactivity, with Xanthosine exhibiting the lowest HOMO-LUMO energy gap. Overall, antioxidant potency and erythrocyte compatibility did not necessarily align, identifying extraction solvent as a critical determinant of the bioactivity-hemocompatibility balance of H. lupulus extracts.

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