EFFECTS OF THE METHANOLIC LEAF EXTRACT OF CAMEL’S FOOT (Piliostigma reticulatum (DC) HOCHST) ON TYPE II DIABETIC ENCEPHALOPATHY IN MALE WISTAR RAT

Abstract

The prevalence rates of diabetes mellitus (DM) have risen markedly in recent years across the globe. Diabetic encephalopathy is one of the most severe microvascular complications of diabetes in the central nervous system (CNS). Piliostigma reticulatum (DC) Hochst is a leguminous plant belonging to the family Caesalpiniaceae and is widely distributed in Africa and Asia. Pharmacologically, P. reticulatum had been reported to possess antioxidant, antimicrobial, antidiarrheal and anti-epileptic properties. However, information linking the protective potential of P. reticulatum against type 2 diabetes complications such as diabetic encephalopathy is very scarce. Hence, this research seeks to investigate the effect of P. reticulatum in rats with induced diabetic encephalopathy. One hundred and eight (108) male albino rats weighing 150-300 g were divided into nine (9) groups (n = 12). Group 1 receives distilled water and serves as the control group. Group 2 rats were administered high fructose solution (10%) for 14 days followed by a single dose of STZ (30 mg/kg b.wt, i.p). Groups 3-6 were also administered fructose/STZ and were treated with crude extract of P. reticulatum (200, 400 and 600 mg/kg b.wt) and glibenclamide (standard drug, 10 mg/kg b wt.), respectively while groups 7-9 received P. reticulatum (200, 400 and 600 mg/kg b.wt) alone. The treatment was carried out orally for 21 days. The animals were sacrificed by cervical dislocation 24 hours after the last treatment and the brains were excised for biochemical, gene expression analyses as well as histopathological examinations. The brain weight and brain-tobody weight ratio were determined. Serum glucose level was evaluated while the tissue homogenates were assessed for dopamine level and activities of tyrosine hydroxylase (TH), acetylcholinesterase (AChE) and myeloperoxidase (MPO). Expression of Tau protein, p38, NF-κB, PI3K and AKT genes were carried out. Results indicated that there was restoration in the brain morphology of STZ-induced encephalopathic rats treated with P. reticulatum when to STZ-toxified group as adjudged by their effects on brain weight and organ-to-body weight vi ratio estimations. The elevated blood glucose occasioned by STZ administration was lowered after treatment with P. reticulatum. There was significant correction in dopamine metabolism and other neurotransmitters as adjudged by their effects on TH, AChE and MPO activities in rats with STZ-induced diabetic encephalopathy treated with the P. reticulatum leaves extract when compared to the rotenone intoxicated group. In addition, a significant gene regulation in the expression of inflammatory genes (Tau protein, p38 and NF-κB) and carbohydrate metabolizing genes (PI3K and AKT) were observed upon treatment with P. reticulatum. Furthermore, consistent trend was seen in the histopathological findings which showed significant attenuation of neuronal cell death in STZ intoxicated rats treated with P. reticulatum. The results of this study demonstrate the protective effect of methanolic leaves extract of P. reculatum against STZ-induced diabetic encephalopathy. The mechanism of action of the plant extract by which it conferred neuroprotection could be via the modulatory effects on neurochemical moderations, as well as antioxidant, anti-inflammatory and antiapoptotic activities.