Jobelyn® Supplement Lowered Neuronal Degeneration: Significance of Altered p53 and ɤ-Enolase Protein Expressions in Prefrontal Cortex of Rat Exposed to Ethanol

Abstract

Background: Alcohol-induced neurodegeneration, a consequence of chronic ethanol exposure, is a neuroadaptation that drives the progression of alcohol use disorder (AUD). Unfortunately, conventional drugs for AUDs do not prevent neurodegeneration as part of their pharmacological repertoire. Multimodal neuroprotective therapeutic agents are hypothesized to have high therapeutic utility in the treatment of central nervous system. Interestingly, nutraceuticals by nature are multimodal in mechanisms of action. Purpose: This study examined the neuroprotective potential of Jobelyn in prefrontal cortex (PFC) of a binge-alcohol rat model of AUD. Methods: Three groups of rats were fed thrice daily through an orogastric tube with 5 g/kg ethanol (25% w/v), 5 g/kg ethanol (25% w/v) plus Jobelyn (4 mg/kg body weight), and 5 g/kg of a nutritionally complete diet (50% v/v), respectively. Cytoarchitectural study of the PFC was done in slides stained with haematoxylin and eosin. Immunohistochemical analyses were performed with mice monoclonal anti-p53 and anti-neuron specific enolase (NSE) antibodies to detect the degree of apoptosis and necrosis in the PFC. In addition, the degree of tissue damage and the level of lipid peroxidation were evaluated. Results: Jobelyn supplementation significantly lowered the levels of histologic and biochemical indices of neurodegeneration, and caused an increased expression of p53 protein and a decreased expression of NSE immunoreactivity (NSE-IR). Conclusions: Jobelyn supplementation ameliorates neurodegeneration in the PFC of AUD rats by reducing the oxidative stress, reducing the NSE-IR, and by increasing the expression of cellular tumor antigen p53 in the cortical neurons.

A Case for the Neuroprotective Potential of African Phytochemicals in the Management of Alzheimer’s Disease

“…It is important to understand that oxidative-mediated reactions are crucial to many key aspects of life processes such as mitochondrial cell respiration, lipid synthesis, lysosome phagocytosis of foreign bodies (immunity and inflammation), and xenobiotic biotransformation of organic/inorganic compounds [79]. However, studies have reported that alterations in these biological processes, as well as excessive intake of substances, such as alcohol (e.g., ethanol) and certain food additives, are associated with up-regulation of oxidative processes and neuroinflammatory mediators that can facilitate the progression of AD [80][81][82].…”

“…JB consumption supports a healthy normalization of many aspects of blood cell production and function when administered at recommended doses [97]. Its strong anti-oxidative, immunomodulatory, and multi-facetted anti-inflammatory properties have been used to treat and manage myriad diseases, ranging from cancer, diabetes, stroke, arthritis, and many other debilitating disorders [81,98,99]. Pharmacological investigations have also shown that JB exhibits neuroprotective properties including anti-amnesic, antidepressant, and anti-psychotic effects [82,98].…”

“…Studies have revealed the mitigating potentials of JB against the neurotoxic effects of scopolamine [100] and attenuating effects against neurodegeneration initiated by chronic alcohol treatment in rodents [81]. Clinically, renowned medications (acamprosate, disulfiram, and naltrexone) for the treatment of AUDs targeted the psychoactive properties of alcohol, while the neurodegenerative effect of alcohol that drives alcohol-induced neurological dysfunction was not reversed by these agents [110].…”

“…Clinically, renowned medications (acamprosate, disulfiram, and naltrexone) for the treatment of AUDs targeted the psychoactive properties of alcohol, while the neurodegenerative effect of alcohol that drives alcohol-induced neurological dysfunction was not reversed by these agents [110]. Intriguingly, JB exhibited reductions in tissue destruction, oxidative stress, neuronal necrosis, and neuronal apoptosis in the corticolimbic pathway in rat models of AUD [81]. Furthermore, the anti-apoptotic effect of JB was reported to provide neuroprotection to environmentally-induced programmed cell death by maintaining neuronal survival via the control of tumor antigen p53 and ɤ-enolase regulated apoptotic and necrotic processes [111].…”

The West African&nbsp;<em>Sorghum Bicolor </em>Leaf Sheath Extract Jobelyn&reg; and Its Diverse Therapeutic Potentials

“…51 Omega-6 fats have pro-inflammatory effects while omega-3 fats have anti-inflammatory effects. The ratio of 3:1 will reduce the chronic inflammation that most people recognize as the root cause of many chronic diseases, including diabetes.…”