Hesperetin, a Selective Phosphodiesterase 4 Inhibitor, Effectively Suppresses Ovalbumin-Induced Airway Hyperresponsiveness without Influencing Xylazine/Ketamine-Induced Anesthesia
Figure 6
Mechanisms of action of hesperetin. Hesperetin selectively inhibits PDE4 activity and results in an increase in cAMP, which activates cAMP-dependent protein kinase (PKA) and increases calcium extrusion from the intracellular space and uptake to sarcoplasmic reticula (SR). Therefore, hesperetin largely decreases the concentration of intracellular calcium ([Ca2+]i) and results in bronchodilation. The increase in cAMP also has anti-inflammatory and immunoregulatory effects. AC: adenylate cyclase; Th: T-helper cells; Ig: immunoglobulin; IL: interleukin; IFN: interferon; TNF: tumor necrosis factor. Up and down arrows, respectively, indicate increases and decreases.
