An in silico investigation on the inhibitory potential of the constituents of Pomegranate juice on antioxidant defense mechanism: Relevance to neurodegenerative diseases

Abstract

Elevation in the levels of reactive oxygen and nitrogen species (RONS), and downregulation of cellular antixoidants, have ubiquitously been reported from studies in animal models of neurodegenerative diseases, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). Thus, plant-derived compounds are widely being investigated for their beneficial effects in these models. However, while studies have reported antioxidant potentials of several phytochemicals, a large number of studies have demonstrated different phytochemicals to be rather pro-oxidant and exaggerate oxidative stress (OS). One such study aimed to investigate possible ameliorative effect of Pomegranate juice (PJ) in rat model of toxin-induced parkinsonism revealed that PJ exacerbates OS, inflammation and promotes neurodegeneration. Thus, it remains to be investigated whether different constituents and metabolites of PJ are pro-oxidant or anti-oxidant. Using computational modeling, we investigated possible inhibitory potential of different constituents of PJ and their metabolites viz. delphinidin-3-glucoside, dimethylellagic acid-glucuronide, ellagic acid, ellagitannin, gallic acid, gallotannin 23, pelargonidin, punicalagin, urolithin A, urolithin A-glucuronide and urolithin B, on anti-oxidant defense system of the brain. The results indicate that the constituents of PJ have the potential to inhibit five key enzymes of the neuronal antioxidant defense system, viz. catalase, superoxide dismutase, glutathione peroxidase 4, glutathione reductase and glutathione-S-transferase. Thus, it is surmised that the constituents of PJ may contribute to OS and neurodegeneration by way of affecting antioxidant defense mechanism. This may particularly be more pronounced in neurodegenerative diseases, since neurons are known to be more vulnerable to OS. Thus, the present findings caution the use of PJ in patients prone to OS, especially those suffering from neurodegenerative diseases, and warrant further experimental studies to unveil the effects of individual components and metabolites of PJ on antioxidant defense system of brain.

The Metabolite Urolithin-A Ameliorates Oxidative Stress in Neuro-2a Cells, Becoming a Potential Neuroprotective Agent

“…Computational studies performed with different pomegranate juice constituents revealed that they can act as pro-oxidants or antioxidants. Molecular docking studies seem to be controversial, as they have determined that urolithin A may inhibit cytosolic enzymes such as catalase, superoxide dismutase, and glutathione [34]; however, urolithin A seems to improve the activity of these enzymes in our present study. With the aim of elucidating molecular mechanisms involved in the cytoprotective and antioxidant properties of urolithin A, peroxiredoxins expression (Prx) was quantified in this work.…”

Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress

“…Results showed that among others, urolithin A, urolithin A glucuronide, and urolithin B have the potential to inhibit catalase, SOD (superoxide dismutase), GR (glutathione reductase), GPx (glutathione peroxidase), and GST (glutathione-S-transferase), by interfering with their active catalytic sites. These findings suggest that these compounds can act both as prooxidants and as antioxidants [42].…”

Control of Reactive Oxygen Species for the Prevention of Parkinson’s Disease: The Possible Application of Flavonoids

“…Pelargonidin alleviates 6-OHDA-induced neurotoxicity through the suppression of lipid oxidation in a rodent model of PD. Blueberry extracts, such as pelargonidin, peonidin, and petunidin, have multiple health-promoting properties, and it has been largely revealed that blueberries and pomegranate extract can protect neurons against neurotoxic events, such as apoptosis, inflammation, and OS ( Table 3 ) [ 187 , 188 , 189 ].…”