Therapeutic potentials of Vernonia amygdalina in thioacetamide-induced neurotoxicity in the CA1 hippocampal subfield via inhibition of microglial activation

Abstract

Thioacetamide (TAA)-induced hepatic encephalopathy (HE) has been reported in several studies. Sequel to acute or chronic liver failure, there is impairment in the hippocampal structure and hippocampal-mediated functions. The precise pathophysiological mechanism leading to neurological alterations remains elusive. The hippocampus also has rarely been examined in HE, hence this study. Vernonia amygdalina (VA) which possesses diverse biological activities has been studied and has promising therapeutic potential in several neurodegenerative diseases. Here, we investigated the neuroprotective activities of Vernonia amygdalina against thioacetamide-induced neuronal damage in the CA1 region of the hippocampus in the rat model. Thirty male Wistar rats were divided into five groups A-E (n=6). Group A (control) was the placebo and was administered 2mL/kg distilled water, group B was administered 100mg/kg thioacetamide only. Groups C-E were administered 100mg/kg of thioacetamide and were subsequently treated with 100mg/kg VA, 200mg/kg VA, and 3mg/kg vitamin C respectively. All administration was carried out for 14 days duration orally. Neurobehavioral tests were conducted. Required brain tissues for biochemical analyses were harvested following rat sacrifice. Glucose-6-phosphate dehydrogenase activity and hippocampal Glutamate levels were evaluated. Histological stains (H&E and cresyl violet) and immunohistochemical expression of Iba-1 protein (microglial marker) were used to assess neuroinflammation and neurodegeneration in the CA1 subfield. Statistical analyses were carried out using Graph pad prism 5 and all results were expressed as Mean±SEM. Means differences were identified by Tukey’s post hoc test. Statistical significance was set at (p< 0.05). The neurobehavioral test results showed an observable increase in anxiety and impaired spatial working memory of the Wistar rats while glutamate (p = 0.6187; F =0.6844) and G6PDH activity (p = 0.6187; F= 0.9486) were not significantly different across groups. Thioacetamide treatment also resulted in neuroinflammation vis-à-vis microglial activation, causing neurodegeneration in the CA1 subfield. Vernonia amygdalina treatment ameliorated these neurotoxic changes. Altogether, Vernonia amygdalina treatment ameliorated thioacetamide-induced neurotoxicity in the CA1 region of the hippocampus via anti-neuroinflammatory and neuroprotective mechanisms.