TY - JOUR
T1 - A New EGFR Inhibitor from Ficus benghalensis Exerted Potential Anti-Inflammatory Activity via Akt/PI3K Pathway Inhibition
AU - Alaaeldin, Rania
AU - Hassan, Heba Ali
AU - Abdel-Rahman, Islam M.
AU - Mohyeldin, Reham H.
AU - Youssef, Nancy
AU - Allam, Ahmed E.
AU - Abdelwahab, Sayed F.
AU - Zhao, Qing Li
AU - Fathy, Moustafa
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Inflammation is a critical defensive mechanism mainly arising due to the production of prostaglandins via cyclooxygenase enzymes. This study aimed to examine the anti-inflammatory activity of fatty acid glucoside (FAG), which is isolated from Ficus benghalensis against lipopolysac-charide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic activity of the FAG on RAW 264.7 macrophages was evaluated with an MTT assay. The levels of PGE2 and NO and the activity of iNOS, COX-1, and COX-2 enzymes in LPS-stimulated RAW 264.7 cells were evaluated. The gene expression of IL-6, TNF-α, and PGE2 was investigated by qRT-PCR. The expression of epidermal growth factor receptor (EGFR), Akt, and PI3K proteins was examined using Western blotting analysisFurthermore, molecular docking of the new FAG against EGFR was investigated. A non-cytotoxic concentration of FAG increased NO release and iNOS activity, inhibited COX-1 and COX-2 activities, and reduced PGE2 levels in LPS-stimulated RAW 264.7 cells. It diminished the expression of TNF-α, IL-6, PGE2, EGFR, Akt, and PI3K. Furthermore, the molecular docking study proposed the potential direct binding of FAG with EGFR with a high affinity. This study showed that FAG is a natural EGFR inhibitor, NO-releasing, and COX-inhibiting anti-inflammatory agent via EGFR/Akt/PI3K pathway inhibition.
AB - Inflammation is a critical defensive mechanism mainly arising due to the production of prostaglandins via cyclooxygenase enzymes. This study aimed to examine the anti-inflammatory activity of fatty acid glucoside (FAG), which is isolated from Ficus benghalensis against lipopolysac-charide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic activity of the FAG on RAW 264.7 macrophages was evaluated with an MTT assay. The levels of PGE2 and NO and the activity of iNOS, COX-1, and COX-2 enzymes in LPS-stimulated RAW 264.7 cells were evaluated. The gene expression of IL-6, TNF-α, and PGE2 was investigated by qRT-PCR. The expression of epidermal growth factor receptor (EGFR), Akt, and PI3K proteins was examined using Western blotting analysisFurthermore, molecular docking of the new FAG against EGFR was investigated. A non-cytotoxic concentration of FAG increased NO release and iNOS activity, inhibited COX-1 and COX-2 activities, and reduced PGE2 levels in LPS-stimulated RAW 264.7 cells. It diminished the expression of TNF-α, IL-6, PGE2, EGFR, Akt, and PI3K. Furthermore, the molecular docking study proposed the potential direct binding of FAG with EGFR with a high affinity. This study showed that FAG is a natural EGFR inhibitor, NO-releasing, and COX-inhibiting anti-inflammatory agent via EGFR/Akt/PI3K pathway inhibition.
KW - Akt/PI3K pathway
KW - EGFR
KW - anti-inflammatory activity
KW - cyclooxygenases
KW - iNOS
UR - http://www.scopus.com/inward/record.url?scp=85133704106&partnerID=8YFLogxK
U2 - 10.3390/cimb44070205
DO - 10.3390/cimb44070205
M3 - 学術論文
C2 - 35877429
AN - SCOPUS:85133704106
SN - 1467-3037
VL - 44
SP - 2967
EP - 2981
JO - Current Issues in Molecular Biology
JF - Current Issues in Molecular Biology
IS - 7
ER -