Disorders of Hippocampus Facilitated by Hypertension in Purine Metabolism Deficiency is Repressed by Naringin, a Bi-flavonoid in a Rat Model via NOS/cAMP/PKA and DARPP-32, BDNF/TrkB Pathways

Abstract

Individuals who are hypertensive have a higher tendency of predisposition to other genetic diseases including purine metabolism deficiency. Therefore, the search for nontoxic and effective chemo protective agents to abrogate hypertension-mediated genetic disease is vital. This study therefore investigated the repressive effect of naringin (NAR) against disorder of hippocampus facilitated by hypertension in purine metabolism deficiency. Male albino rats randomly assigned into nine groups (n = 7) were treated for 35 days. Group I: control animals, Group II was treated with 100 mg/kg KBrO₃, Group III was treated with 250 mg/kg caffeine, and Group IV was treated with 100 mg/kg KBrO₃ + 250 mg/kg caffeine. Group V was administered with 100 mg/kg KBrO₃ + 100 mg/kg haloperidol. Group VI was administered with 100 mg/kg KBrO₃ + 50 mg/kg NAR. Group VII was administered with 250 mg/kg caffeine + 50 mg/kg NAR, and Group VIII was administered with 100 mg/kg KBrO₃ + 250 mg/kg caffeine + 50 mg/kg NAR. Finally, group IX was treated with 50 mg/kg NAR. The sub-acute exposure to KBrO₃ and CAF induced hypertension and mediated impairment in the hippocampus cells. This was apparent by the increase in PDE-5¹, arginase, and enzymes of ATP hydrolysis (ATPase and AMPase) with a simultaneous increase in cholinergic (AChE and BuChE) and adenosinergic (ADA) enzymes. The hypertensive-mediated hippocampal impairment was associated to alteration of NO and AC signaling coupled with lower expression of brain-derived neurotrophic factor and its receptor (BDNF-TrkB), down regulation of Bcl11b and DARPP-32 which are neurodevelopmental proteins, and hypoxanthine accumulation. However, these features of CAF-mediated hippocampal damage in KBrO₃-induced hypertensive rats were repressed by post-treatment with NAR via production of neuro-inflammatory mediators, attenuation of biochemical alterations, stabilizing neurotransmitter enzymes, regulating NOS/cAMP/PKA and DARPP-32, BDNF/TrkB signaling, and restoring hippocampal tissues.

Keywords: Caffeine; Hypertension; Iso-biflavonoid; KBrO3; Neurotropic factor; Purine metabolism deficiency.