Demethylasterriquinone B1

Demethylasterriquinone B1 (DAQ B1; L-783281) is an orally active insulin receptor (insulin receptor) agonist and AKT activator. By activating AKT, Demethylasterriquinone B1 upregulates the expression and activity of eNOS to increase NO production, while downregulating the expression of the NADPH oxidase subunit p22phox to reduce oxidative stress and improve vascular endothelial dysfunction in hypertensive rats. Demethylasterriquinone B1 combind with an AKT inhibitor targets the insulin signaling pathway to activate two antiviral pathways, RNA interference and JAK/STAT, in mosquitoes, thereby reducing Zika virus infection^[1][2][3]. In Vitro:Demethylasterriquinone B1 (1 μM; 24 h) activates the AKT/FOXO insulin signaling pathway, increases the phosphorylation level of ERK, and upregulates the RNAi marker AGO2 in Aedes aegypti Aag2 cells^[2].
Demethylasterriquinone B1 (1 μM; 24 h) significantly reduces Zika virus replication levels in Aedes aegypti Aag2 cells on day 1 and day 3 post-infection^[2].
Demethylasterriquinone B1 (1 μM; 24 h) exerts antiviral activity against Zika virus in Aedes aegypti Aag2 cells, and this activity depends on functional RNAi and JAK/STAT signaling pathways^[2].
Demethylasterriquinone B1 (10-50 µM) effectively reverses insulin resistance induced by PC-1 overexpression and TNF-α inflammation in HTC-IR cells, but has no effect on resistance induced by PKC activation^[3]. In Vivo:Demethylasterriquinone B1 (5 mg/kg; p.o.; once daily; 1 week) ameliorates hypertension-related vascular endothelial dysfunction in male Sprague Dawley rats by restoring eNOS activity, alleviating oxidative stress, and reducing mean arterial pressure, and its effects are dependent on eNOS activity^[1].
Combination treatment with demethylasterriquinone B1 (10 μM; p.o.; single administration) and an AKT inhibitor reduces ZIKV infection rate and viral titer in Aedes aegypti, and induces activation of the RNAi and JAK/STAT antiviral pathways, with the induction level of immune genes peaking at 7 days post-infection^[2].