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5-Methoxyflavone, belonged to Flavonoid family, is a DNA polymerase-beta inhibitor and neuroprotective agent against beta-amyloid toxicity. possess central nervous system (CNS) depressant effect mediated through the ionotropic GABAA receptors.

5-Methoxyflavone (compound 1) is identified as a candidate compound endowed with the ability to inhibit DNA pol-β in multiple and to prevent cell-cycle initiation and subsequent neuronal apoptosis in Aβ-challenged primary neuronal cultures. 5-methoxyflavone (10-30 μM) is able to significantly enhance toxicity of MMS on 92TAg cells. 5-Methoxyflavone (1 or 10 μM) significantly reduces polymerase activity on a gapped substrate[1].5-Methoxyflavone (5-MF, 0-100 μg/mL) results in a time dependent reduction in the levels of antiapoptotic proteins cFLIP, Mcl-1 and an increase in the proapoptotic protein BAX. 5-MF induces both TRAIL-R1(DR4) and TRAIL-R2 (DR5) in a time-dependent manner[2].

5-Methoxyflavone (100, 150 mg/kg, i.p) significantly decreases the latency time to loss of righting reflex. 5-Methoxyflavone (50, 100 and 150 mg/kg, i.p) exhibits a significant and dose-dependent reduction in the spontaneous locomotor activity. 5-Methoxyflavone (50, 100 mg/kg, i.p) reduces the rearing response. 5-Methoxyflavone (100, 125 and 150 mg/kg, i.p) completely abolishesed the grooming response similar to diazepam treated animals[3].

[1]. Merlo S, et al. Identification of 5-Methoxyflavone as a Novel DNA Polymerase-Beta Inhibitor and Neuroprotective Agent against Beta-Amyloid Toxicity. J Nat Prod. 2015 Nov 25;78(11):2704-11. [2]. Shanmugasundaram J, et al. Sedative-hypnotic like effect of 5-methoxyflavone in mice and investigation on possible mechanisms by in vivo and in silico methods. Biomed Pharmacother. 2018 Dec;108:85-94. [3]. Wudtiwai B, et al. Methoxyflavone derivatives modulate the effect of TRAIL-induced apoptosis in human leukemic cell lines. J Hematol Oncol. 2011 Dec 21;4:52.

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