Hcyb1 is a potent and specific inhibitor of phosphodiesterase 2 (PDE2). It exhibits a high degree of selectivity for inhibiting PDE2A with an IC50 value of 0.57 μM. In addition, Hcyb1 displays over 250-fold selectivity against other recombinant members of the PDE family. Moreover, its pharmacological actions include neuroprotective and antidepressant-like effects, which are believed to be mediated through the cAMP/cGMP-CREB-BDNF signaling pathway [1].

Hcyb1 significantly enhances cGMP levels by 1.7 to 2.3 folds within 10 minutes of exposure at concentrations ranging from 1 to 100 nM, as well as increases both cGMP and cAMP levels after 24 hours at a concentration of 1 nM. Furthermore, Hcyb1 treatment elevates the phosphorylation levels of CREB and BDNF in HT-22 cells over a 24-hour period and promotes HT-22 cell viability along with cGMP and cAMP accumulation. Its effects on cell viability are concentration- and time-dependent, as shown by increased cell viability at 0.1 and 1 nM concentrations after 24 hours, particularly noticeable from 12 to 24 hours at 1 nM, reaching maximal effects at 24 hours. Western blot analysis reveals that at a concentration of 1 nM, Hcyb1 significantly augments the phosphorylation of CREB and upregulates BDNF expression in HT-22 cells after 24 hours.

Hcyb1, at doses of 0.5, 1, and 2 mg/kg administered through gavage (i.g.), was found to significantly reduce immobility time in the forced swimming and tail suspension tests, indicating an antidepressant-like activity. This effect was observed without any changes to locomotor function. The study utilized male imprinting control region (ICR) mice weighing between 20 and 25 g as the animal model. The results demonstrate a dose-dependent decrease in immobility time at the administered doses, highlighting Hcyb1's potential therapeutic effect [3].