NEUROBEHAVIOURAL AND NEUROPROTECTIVE EFFECTS OF KOLAVIRON IN LABORATORY RODENTS

Abstract

The high cost of orthodox medicines and their attendant side effects in some cases make the search for an effective and affordable alternative imperative. Kalaviron, a complex biflavanoid from Garcinia kola seeds, possesses hepatoprotective and antidiabetic properties. However, there is paucity of information on its effects on the nervous system. The antinociceptive, neurobehavioural and neuroprotective effects produced by kolaviron and its possible mechanism of action were evaluated in laboratory rodents. Garcinia kola seeds were air-dried, powdered and extracted in Soxhlet to obtain methanol fraction. The fraction was partitioned in chloroform:distilled water (3:1). The chloroform portion was concentrated to give a golden yellow substance called Kolaviron (KV). Male Wistar rats (180-220 g) and Swiss mice (18-25 g) grouped into five groups of six animals each were treated with normal saline (10 ml/kg, p.o.), kolaviron (50, 100 and 200 mg/kg, p.o.) and indomethacin (10 mg/kg, i.p). Psychoemotional stress was induced using the whisker removal technique. Antinociceptive activity was studied using the hot plate, tail flick and acetic acid-induced writhing tests. Neurobehavioural properties were observed using the openfield, elevated plus-maze, light/dark box and hole board methods. Brain tissue levels of reduced glutathione (GSH). catalase and malodialdehyde were estimated using spectrophotometric method. Histological analysis of the frontal cortex and cerebellum stained with haematoxylin and eosin were observed using light microscope. Data were analysed using ANOVA and Newman-Keul’s post-hoc test at α0.05. Kolaviron dose dependently prolonged tail flick latencies by 23.5, 45.0 and 53.5% relative to control and hot plate latencies by 41.5, 125.5 and 217.9% relative to control. Kolaviron inhibited acetic acid- induced writhings by 6.6, 14.5 and 31.8% relative to control. Reductions in frequencies of locomotion (69.0±6.0, 64.5±3.3 and 52.3±5.8 vs 76.2 ± 3.2), rearing (22.2±1.5, 15.8±3.8 and 17.5±3.9 vs 30.7±3.7) and grooming (5.7±1.0, 5.7±0.8 and 3.3±0.4 vs 13.3±0.8) were observed in the openfield, so also were reductions in head dip frequencies in the hole board (19.1±1.3, 19.6±1.5 and 15.5±1.3 vs 37.1±1.7). In the elevated plus-maze, kolaviron reduced the time spent in the open-arm (55.1±4.5, 40 ± 3.5 and 25.5 ± 4.1) compared with control (65.1±3.3s). Significant reductions were observed in the time spent in, the light arena of the light/dark box (80.8±8.5, 70.5±5.2 and 51.3 ±25.5) compared with the control (180.5±25.5s). Malondialdehyde (U/mg protein) levels in the cerebellum (6.5±0.4) and the frontal cortex (30.1± 4.7) of stressed animals were significantly higher compared with their control values (3.8±0.2 and 14.6±2.5, respectively). Catalase and GSH levels in the cerebellum and frontal cortex of the treated animals were significantly lower than their controls. Kolaviron pre-treatment significantly attenuated all these changes in Malondialdehyde, Catalase and GSH levels. Some of the stress-induced histological abnormalities like vacuolation, vascular congestion and appearance of abnormal Purkinje cells were partially reduced by kolaviron. Kolaviron exhibited positive antinociceptive and neurobehavioral effects mediated through sedation and neuroprotective effects via mechanisms that involve- inhibition of oxidative stress.