8-​O-​Acetylharpagide

8-O-Acetylharpagide is an orally active iridoid glycoside compound. 8-O-Acetylharpagide exhibits anti-aging activity at low doses and anticancer activity at high doses. 8-O-Acetylharpagide induces late-stage apoptosis and necrosis-like death in cancer cells, and downregulates anti-apoptotic proteins such as Akt, p-Akt and Bcl-2. 8-O-Acetylharpagide is mainly metabolized in rats via demethylation, hydrolysis and glucuronidation, and its active metabolites downregulate the AKT/NF-κB/MMP9 signaling axis. 8-O-Acetylharpagide exerts vasoconstrictive effects by activating vascular α-adrenoceptor^[1][2][3]. In Vitro:8-O-acetylharpagide (0.5-10 μM; 48 h) dose-dependently inhibits the activity of senescence-associated β-galactosidase in senescent human dermal fibroblasts in vitro^[1].
8-O-acetylharpagide (0.5-10 μM; 48 h) dose-dependently inhibits p53 expression in senescent human dermal fibroblasts^[1].
8-O-acetylharpagide (1-10 μM) inhibits the elevated intracellular reactive oxygen species levels in dermal fibroblasts from elderly humans^[1].
8-O-acetylharpagide (2.5 mg/mL; 0-24 h) undergoes metabolic transformation in an in vitro rat intestinal flora culture system, producing 2 metabolites via pathways including hydrolysis, reduction and glucuronidation^[2].
8-O-acetylharpagide (0.01-1 mM; 24 h) exhibits more potent selective cytotoxicity against human hypopharyngeal carcinoma FaDu cells than against normal human PDL cells, with an IC₅₀ of 0.88 mM for FaDu cells and 1.65 mM for PDL cells after 24 h of treatment^[3].
8-O-acetylharpagide (1 mM; 24 h) induces significant cell rounding in human hypopharyngeal carcinoma FaDu cells, but exerts no such effect in normal human PDL cells^[3].
8-O-acetylharpagide (1 mM; 6 days) completely inhibits the proliferation of human hypopharyngeal carcinoma FaDu cells^[3].
8-O-acetylharpagide (0.5-1 mM; 24 h) induces dose-dependent G2/M phase arrest in human hypopharyngeal carcinoma FaDu cells and regulates the expression of cell cycle-related proteins, but exerts no effect on the cell cycle distribution of normal human PDL cells^[3].
8-O-acetylharpagide (1 mM; 24 h) induces significant necroptotic cell death and late apoptosis in human hypopharyngeal carcinoma FaDu cells, downregulates anti-apoptotic proteins, but exerts minimal effects on normal human PDL cells^[3].
8-O-acetylharpagide (1 mM; 24 h) significantly enhances the radiosensitivity of human hypopharyngeal carcinoma FaDu cells, but has no effect on that of normal human PDL cells^[3]. In Vivo:8-O-acetylharpagide (75-150 mg/kg; p.o.; once daily; for 4 consecutive weeks) significantly inhibits the AKT/NF-κB/MMP9 signaling axis in 4T1 breast cancer-bearing Balb-C mice^[2].
8-O-acetylharpagide (low dose; p.o.) inhibits senescent phenotypes in aged mice^[3].