Targeted inhibition of PI3K/Akt by luteolin-rich Hydrilla verticillata in TNF-α and IFN-γ-induced atopic keratinocytes
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초록

Hydrilla verticillata (HV) contains bioactive compounds, yet its anti-inflammatory potential and the most active solvent fraction remain underexplored. This study evaluated the anti-inflammatory effects of the HV ethyl acetate fraction (HV-EtOAc) in TNF-α and IFN-γ-stimulated HaCaT keratinocytes and through in silico analysis. Bioactive components were identified using ultra-performance liquid chromatography–tandem mass spectrometry and quantified by high-performance liquid chromatography. Among the solvent fractions, HV-EtOAc exhibited the strongest inhibitory effects on inflammatory mediators, reducing IL-6 (33–46%), IL-8 (25%), and MCP-1 (36–79%) production. Gene expression analysis revealed downregulation of key chemokines and cytokines, including MCP1, RANTES, TARC, MDC, CTACK, and IL6. HPLC analysis showed HV-EtOAc contained significantly higher luteolin levels (2.44 ± 0.01 mg/g) than the crude ethanolic extract (0.94 ± 0.01 mg/g). Luteolin alone suppressed IL-6 (62.7–88.2%), IL-8 (82.9–94.0%), and MCP-1 (78.3%) production in vitro. Molecular docking indicated strong binding affinity of luteolin to Akt. Western blot analysis confirmed that HV-EtOAc inhibited phosphorylation in the PI3K/Akt, NF-κB (IκBα and p65), and MAPK (ERK, JNK, and p38) signaling pathways. These findings suggest that the luteolin-enriched HV-EtOAc fraction exerts potent anti-inflammatory effects by targeting multiple signaling pathways involved in cytokine production. This study highlights the potential of H. verticillata, particularly its ethyl acetate fraction, as a promising natural source for therapeutic agents against inflammatory skin disorders.

키워드

Aquatic weedAtopic dermatitisFractionationInflammatory skin diseaseNetwork pharmacologySecondary metaboliteANTIOXIDANT ACTIVITYEXTRACTIONEXPRESSION
제목
Targeted inhibition of PI3K/Akt by luteolin-rich Hydrilla verticillata in TNF-α and IFN-γ-induced atopic keratinocytes
저자
Yu, HyeonjunTonog, GenevieveKakooza, DerrickJeong, WonsikHong, Seong SuKim, Woo JungSuh, Hyung-JooLee, SanghyunMoon, Sung-KwonKim, Hoon
DOI
10.1016/j.fitote.2026.107147
발행일
2026-04
유형
Article
저널명
Fitoterapia
190