Phytochemical Phosphodiesterase Inhibitors: A Comprehensive Review of Molecular Mechanisms and Therapeutic Potential
Abstract
Phosphodiesterase (PDEs), a superfamily of enzymes, catalyze the hydrolysis of cyclic nucleotides, specifically guanosine 3',5'-cyclic monophosphate (cGMP), adenosine 3',5'-cyclic monophosphate (cAMP) thereby playing a critical role in the precise intracellular signaling cascades regulation and consequently, cellular function. The identification of 11 distinct PDE isoenzyme families, each exhibiting unique substrate specificities, tissue distributions, and regulatory mechanisms, has significantly advanced our understanding of their physiological and pathophysiological roles at the cellular and molecular levels. This increased knowledge has facilitated the way for the emergence of highly selective PDE isoenzyme inhibitors, offering promising therapeutic avenues for a wide range of diseases. PDE inhibitors include many pharmacological agents and they are widely used due to their many pharmacological effects like pleiotropic, vasodilator, cardio tonic, smooth muscle relaxant, antidepressant, anti-inflammatory, antithrombotic and cognitive-enhancing properties. On clinical side, PDE inhibitors have validated efficacy in the management of various conditions, including erectile dysfunction, chronic obstructive pulmonary disease (COPD), and pulmonary arterial hypertension and Alzheimer's disease. Most importantly, with the advancements of indications, states that vast variety of pharmacologically active phytochemicals derived from various plants produce PDE inhibitory activity. All…
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