The anti-depressant effects of a novel PDE4 inhibitor derived from resveratrol
Abstract
Context: Resveratrol has shown anti-stress and anti-depressant-like abilities involved in inhibiting phosphodiesterase-4 (PDE4) enzyme. However, its application is limited due to its low efficacy, bioavailability and selectivity.
Objective: This study synthesized a new resveratrol derivative RES003 and evaluated its PDE4 inhibitory and anti-depressant-like activities in vitro and in vivo, respectively.
Materials and methods: PDEs inhibitory activities were evaluated by radioactive tracer method. Anti-depressant-like activities of novel resveratrol analogue (RES003) at doses of 2.5, 5.0 and 10 mg/kg was investigated by sugar water consumption and forced swimming tests using male ICR mice under chronic unpredictable stress procedure for 10 days. A total of 84 mice were randomly distributed into seven groups (n = 12). Drugs and vehicle were administered (intra-gastric or intra-peritoneal) once a day from the first to the last day. The molecular mechanisms were identified by western blot.
Results: RES003 showed more potent PDE4 inhibitory activity (half maximal inhibitory concentration (IC50), 0.87 μM) and better selectivity than resveratrol (IC50, 18.8 μM). RES003 could significantly increase the consumption of sugar water (p p p p < 0.05 and 0.01) in mouse brain.
Discussion and conclusions: RES003 could ameliorate chronic stress induced depression-like behaviours through inhibition of PDE4 and activation of cAMP-triggered phosphorylation of cAMP response element binding…
How strong is the evidence?
Evidence Hub reads this as a report, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health. Reported size: 12 participants or records.
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