Dose-dependent neuroprotective effect of oriental phyto-derived glycyrrhizin on experimental neuroterminal norepinephrine depletion in a rat brain model

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Ahmed-Farid, Omar A.
Haredy, Shimaa A.
Niazy, Reham M.
Linhardt, Robert J.
Warda, Mohamad
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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The dose-dependent neuroprotective role of licorice-derived glycyrrhizin during subacute neuroterminal norepinephrine (NE) depletion was studied in rat brain. Experimental design included thirty 5-week-old male rats randomly divided into five groups. Compared to the saline-injected control group, the group receiving daily intraperitoneal injection of fusaric acid (FA; 5 mg/kg/b.w.) for 30 days showed pharmacological depletion of NE. The neuroprotective effects of three successively increasing oral doses of glycyrrhizin were examined in FA-treated rats. Neurochemical parameters and histo-/immunohistopathological changes in the hippocampus were examined. FA generated global hippocampal stress with altered neurobiochemical parameters, accompanied by immune-confirmed inflammatory tissue damage, and noticeable behavioral changes. Although glycyrrhizin after FA-induced intoxication did not correct the recorded drop in the NE level, it decreased the dopamine levels to control levels. Similarly, glycyrrhizin at a high dose restored the serotonin level to its normal value and blocked the FA-induced increase in the level of its metabolite, 5-hydroxyindoleacetic acid. The FA-induced rise in γ-aminobutyric acid (GABA) and histamine was alleviated after administration of a high dose of glycyrrhizin. This was accompanied by improvements in the bioenergetic status and neuronal regenerative capacity through recovery of ATP and brain-derived neurotrophic factor levels to the pre-intoxicated values. High doses of glycyrrhizin also ameliorated the FA-generated behavioral changes and oxidative damage, manifested by the reduction in the expression of cortical pro-apoptotic caspase 3 in the same group. This study suggests that glycyrrhizin can potentially mend most of the previously evoked neuronal damage induced by FA intoxication in the brain of an experimental rat model.
Chemico-Biological Interactions, 308, 279–287
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Dose-dependent neuroprotective effect of oriental phyto-derived glycyrrhizin on experimental neuroterminal norepinephrine depletion in a rat brain model, O. A. Ahmed-Farid, S. A. Haredy, R. M. Niazy, R. J. Linhardt, M. Warda, Chemico-Biological Interactions, 308, 279–287, 2019.
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