Title:Natural Molecules as Talented Inhibitors of Nucleotide Pyrophosphatases/
Phosphodiesterases (PDEs)
Volume: 22
Issue: 3
Author(s): Ilkay Erdogan Orhan*, Abdur Rauf*, Muhammad Saleem and Anees Ahmed Khalil
Affiliation:
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey
- Department of Chemistry, University of Swabi, Anbar, 25120, KPK, Pakistan
Keywords:
Phosphodiesterase, Enzyme inhibitors, Secondary metabolites, Natural molecules, CAMP, cGMP.
Abstract:
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).
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.