Development of a caffeic acid–phthalimide hybrid compound for NADPH oxidase inhibition

The incorporation of the phthalimide moiety into caffeic acid was decisive for its effectiveness as an NADPH oxidase inhibitor.

Apocynin Treatment Prevents Cardiac Connexin 43 Hemichannels Hyperactivity by Reducing Nitroso-Redox Stress in Mdx Mice

Duchenne muscular dystrophy (DMD) is a fatal disease that causes cardiomyopathy and is associated with oxidative stress. In the heart, oxidative stress interferes with the location of connexin 43 (Cx43) to the intercalated discs causing its lateralization to the plasma membrane where Cx43 forms hemichannels. We tested the hypothesis that in DMD cardiomyopathy, increased oxidative stress is associated with the formation and activation of Cx43 hemichannels. For this, we used mdx mice as a DMD model and evaluated cardiac function, nitroso-redox changes and Cx43 hemichannels permeability. Mdx hearts presented increased NADPH oxidase-derived oxidative stress and increased Cx43 S-nitrosylation compared to controls. These redox changes were associated with increased Cx43 lateralization, decreased cardiac contractility and increased arrhythmic events. Pharmacological inhibition of NADPH oxidase using apocynin (one month) reduced systemic oxidative stress and reversed the aforementioned changes towards normal, except Cx43 lateralization. Opening of Cx43 hemichannels was blocked by apocynin treatment and by acute hemichannel blockade with carbenoxolone. NADPH oxidase inhibition also prevented the occurrence of apoptosis in mdx hearts and reversed the ventricular remodeling. These results show that NADPH oxidase activity in DMD is associated with S-nitrosylation and opening of Cx43 hemichannels. These changes lead to apoptosis and cardiac dysfunction and were prevented by NADPH oxidase inhibition.

The Anti-inflammatory Potential of Selected Plant-derived Compounds in Respiratory Diseases

: Inflammation plays a major role in chronic airway diseases like asthma, COPD, and cystic fibrosis. Inflammation plays a crucial role in the worsening of the lung function resulting in worsening symptoms. The inflammatory process is very complexed, therefore the strategies for developing an effective treatment for inflammatory airway diseases would benefit from the use of natural substances. : Parthenolide, apocynin, proanthocyanidins, and boswellic acid present different mechanisms of actions - among others, through NF-κB or NADPH oxidase inhibition, therefore showing a wide range of applications in various inflammatory diseases. Moreover, some of them have also antioxidant properties. : Naturally occurring substances may exert some anti-inflammatory effects by modulating some of the inflammatory pathways. These agents have been used in different cultures for thousands of years and have proven to be relatively safe. : Parthenolide, apocynin, proanthocyanidins, and boswellic acid present different mechanisms of actions - among others, through NF-þB or NADPH oxidase inhibition, therefore showing a wide range of applications in various inflammatory diseases. Moreover, some of them have also antioxidant properties. : This review provides an overview of the anti-inflammatory effects of some of the natural agents and illustrates their great potential as sources of drugs to cover an extensive range of pharmacological effects.