Natural Molecules as Talented Inhibitors of Nucleotide Pyrophosphatas-es/Phosphodiesterases (PDEs)

Background: Phosphodiesterases (PDEs) are a wide group of enzymes with multiple therapeutic actions, including vasorelaxation, cardiotonic, antidepressant, anti-inflammatory, antithrombotic, anti-spasmolytic, memory-enhancing, and anti-asthmatic. PDEs with eleven subtypes from PDE-1 to PDE-11 typically catalyze the cleavage of the phosphodiester bond and, hence, degrades either cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP). 10.2174/1568026621666210909164118 Objective: Several selective or non-selective inhibitors of the PDE subtypes are used clinically, i.e. sildenafil, rolipram, cysteine, etc. Recently, interest in plant-based pharmacologically bioactive compounds having potent PDEs inhibitory potential has increased. Purposely, extensive research has been carried out on natural products to explore new inhibitors of various PDEs. Therefore, this review summarizes the published data on natural PDEs inhibitors and their potential therapeutic applications. Methods: For this purpose, natural compounds with PDE inhibitory potential have been surveyed through several databases, including PubMed, Web of Sciences (WoS), Scopus, and Google Scholar. Results: According to a detailed literature survey, the most promising class of herbal compounds with PDE-inhibiting property has been found to belong to phenolics, including flavonoids (luteolin, kaempferol, icariin, etc.). Many other encouraging inhibitors from plants have also been identified, such as coumarins (23, 24) (licoarylcoumarin and glycocoumarin,), saponins (agapanthussaponins), lignans (31, 33) [(+/-)-schizandrin and kobusin], terpenes (28, 29, 31) (perianradulcin A, quinovic acid, and ursolic acid), anthraquinones (18, 19) (emodin and chrysophanol), and alkaloids (Sanjoinine-D) (36). Conclusion: In this review, studies have revealed the PDE-inhibitory potential of natural plant extracts and their bioactive constituents in treating various diseases; however, further clinical studies comprising synergistic use of different therapies (synthetic & natural) to acquire multi-targeted results might also be a promising option.

Automated summary

This review summarizes the potential therapeutic applications of natural plant extracts and their bioactive constituents as PDE inhibitors. The most promising class of compounds with PDE-inhibiting property belongs to phenolics, including flavonoids, while other plant compounds like coumarins, saponins, lignans, terpenes, anthraquinones, and alkaloids have also shown inhibitory effects. Further clinical studies exploring the synergistic use of different therapies are recommended to achieve multi-targeted results.