Nonsteroidal anti-inflammatory drugs as potential ecto-nucleotide phosphodiesterase inhibitors

Abstract

Phosphodiesterases (PDE) are group of enzymes which catalyze the hydrolysis of cAMP and cGMP. Since these cyclic phosphate moieties worked as intracellular second messengers in numerous physiological processes, their inhibition can affect normal physiology of living system. NSAIDs are among the frequently prescribed medications, because of their efficacy as analgesic, antipyretic and anti-inflammatory agents. They are known to block cyclooxygenase pathway. In limited data NSAIDs has been shown anti-tumor potential, and phosphodiesterase inhibition has assumed to be one of the mechanism. To date no further evaluation being done. Further, NSAIDs are classified as cyclooxygenase inhibitors and phosphodiesterase inhibition can imprint its side effects. This study first time investigates the effects of NSAIDs on phosphodiesterase 1 inhibition. The activity against snake venom phosphodiesterase 1 was assayed on a microtitre plate reader spectrophotometer. Selective COX-2 inhibitor, celecoxib, exhibited a potent PDE1 inhibitory activity, at therapeutic doses, with an IC 50 value of 29.4 µM. The findings of our study are indicative of new pharmacological actions of cyclooxygenase inhibitors. This article presents the PDE inhibitory properties as a new effects of already existing drugs. These additional effects could be potentially helpful for researchers to assess other physiological and pathological states.

Vascular and pulmonary effects of ibuprofen on neonatal lung development

“…This unexpected finding may be explained indirectly via a dampening of the inflammatory response by ibuprofen, thereby preserving endothelial cell integrity and function, and reducing smooth muscle cell proliferation and contraction [53]. Alternatively, the beneficial effect on vascular remodeling can also be mediated via ibuprofen's offtarget effect of elevating intracellular cGMP levels via cGMP-selective phosphodiesterase (PDE) inhibition [54,55]. This explanation is supported by the beneficial effects of agents that increase intracellular cGMP levels, either by stimulating the NO-eNOS-cGMP pathway with inhaled NO, apelin or soluble guanylate cyclase modulators or inhibiting cGMP breakdown with the specific cGMP-selective PDE5 inhibitor sildenafil, in newborn rats with experimental BPD that our group and others described previously [9,50,[56][57][58].…”

In vitro Antioxidant Activity and In vivo Anti-inflammatory Effect of Ricinus communis (L.) and Withania somnifera (L.) Hydroalcoholic Extracts in Rats

“…Edema formation is a consequence of an inflammatory mediator's interaction that promotes vascular permeability and blood flow [1,2]. Various synthetic drugs such as NSAIDs have good efficacy in inflammatory conditions but also exert some deleterious effects including gastrointestinal problems [3]. Hence, herbal remedies have always been important in Asian countries.…”

In vitro Antioxidant and Anti-Inflammatory Activities of Aqueous Leaf Extract of Alchornea cordifolia

“…Inflammation is the process by which the body respond to injurious stimuli like pathogens, irritants, or damaged cells (Newton and Dixit 2012). Inflammatory actions are generated and maintained through the action of mediators such as histamine, kinins, cytokines, eicosanoids, calcitoningene-related peptide, substance-P, and platelet-activating factor, derived from leukocytes and damaged tissues (Tasneem et al, 2020) Inflammation can lead to edema and infiltration of the white blood cells (Greten and Grivennikov ,2019), Various drugs such as NSAIDs have been used to treat Inflammation, however they exert certain toxic effect such as gastrointestinal problems, Therefore, herbal drugs have been crucial in treatment of inflammation especially in Asian and African countries (Hussain et al, 2021). Herbal Medicines are classes of drugs which use have increase dramatically over the past years.…”