Biosynthetic 3′-O-Me-EC-5-O-β-glucuronide improves basal synaptic transmission and long-term potentiation coinciding with increased CREB hyperphosphorylation. A–D, The effect of 300 nm 3′-O-Me-EC-Gluc treatment on basal neuronal transmission and LTP in hippocampal slices from AD (A, B) and wild-type (Wt) mice (C, D). Arrow indicate the beginning of tetanus to induce LTP. E–I, The effect of 3′-O-Me-(-)-EC-5-O-β-glucuronide on CREB signaling pathway in hippocampal slices from old Tg2576 mice following 5 h 300 nm 3′-O-Me-EC-Gluc treatment. The levels of phosphor-proteins of CREB phosphorylation at Ser133 (E), Erk1/2 phosphorylation at Thr185/Tyr187 (F), MEK phosphorylation at Ser222 (G). H, I, PKA activity and protein content of PKA IIa subunit expression (H) and phosphor-CaMKII and total CaMKII (I) in brain slices from Tg2576 mice. Inset, representative Western blot image of P-CaMKII and total CaMKII. *p < 0.05, n = 5 per group.