The anti-depressant effects of a novel PDE4 inhibitor derived from resveratrol

Figures & data

Figure 1. The structures of resveratrol and RES003.

Scheme 1. Synthesis of RES003. Reagents and conditions: (a) PPTs, CH₂Cl₂, room temperature; (b) NaOH, CH₃OH, reflux; (c) PPTs, C₂H₅OH, 50 °Cand (d) hydrazine hydrate, CH₃COOH, C₂H₅OH, reflux.

Figure 2. Binding mode of compound resveratrol and RES003 within the active pocket of PDE4 (PDB ID: 1UDU). Hydrogen bonds are represented by dashed lines.

Figure 3. The anti-depressant-like effects of RES003 in mice. Mice were treated with vehicle, RES003, and fluoxetine 30 min before being subjected to the (A) SPT and (B) FST. (C) Mice were treated with various doses of RES003 30 min before the locomotor activity test. Results are expressed as mean ± SEM (n = 9–10). ^##p < 0.05 and ^###p < 0.001 versus vehicle-treated control group. *p < 0.05 and **p < 0.01 versus model group. K: control; M : CUS model; Flu: fluoxetine.

Figure 4. Effects of RES003 on CUS-induced decreases in the ratio of pCREB/CREB and BDNF expression in the brain tissue. Results are expressed as mean ± SEM (n = 9–10). ^##p < 0.05 versus vehicle-treated control group. *p < 0.05 versus model group. Rol: rolipram.