Garcinia kola seeds may prevent cognitive and motor dysfunctions in a type 1 diabetes mellitus rat model partly by mitigating neuroinflammation

Abstract

Background We reported recently that extracts of seeds of Garcinia kola, a plant with established hypoglycemic properties, prevented the loss of inflammation-sensible neuronal populations like Purkinje cells in a rat model of type 1 diabetes mellitus (T1DM). Here, we assessed G. kola extract ability to prevent the early cognitive and motor dysfunctions observed in this model. Methods Rats made diabetic by single injection of streptozotocin were treated daily with either vehicle solution (diabetic control group), insulin, or G. kola extract from the first to the 6th week post-injection. Then, cognitive and motor functions were assessed using holeboard and vertical pole behavioral tests, and animals were sacrificed. Brains were dissected out, cut, and processed for Nissl staining and immunohistochemistry. Results Hyperglycemia (209.26 %), body weight loss (-12.37 %), and T1DM-like cognitive and motor dysfunctions revealed behavioral tests in diabetic control animals were not observed in insulin and extract-treated animals. Similar, expressions of inflammation markers tumor necrosis factor (TNF), iba1 (CD68), and Glial fibrillary acidic protein (GFAP), as well as decreases of neuronal density in regions involved in cognitive and motor functions (-49.56 % motor cortex, -33.24 % medial septal nucleus, -41.8 % /-37.34 % cerebellar Purkinje /granular cell layers) were observed in diabetic controls but not in animals treated with insulin or G. kola. Conclusions Our results indicate that T1DM-like functional alterations are mediated, at least partly, by neuroinflammation and neuronal loss in this model. The prevention of the development of such alterations by early treatment with G. kola confirms the neuroprotective properties of the plant and warrant further mechanistic studies, considering the potential for human disease.

Review of the Effect of Natural Compounds and Extracts on Neurodegeneration in Animal Models of Diabetes Mellitus

“…Similar outcomes have been reported when Hedera nepalensis extract is administered to STZ-aluminium trichloride rat model [176]. Likewise, grape seed proanthocyanidin extract [177], kola nut extract [178] or Garcinia kola seeds [155] also improve cognitive impairment in diabetic rat models. Andrographis paniculata extract, enriched in andrographolide, improves cognitive function in STZ-treated rats and the effect seems to be mediated by reducing oxidative stress and acetylcholinesterase activity [175].…”

“…Pouteria ramiflora extract administration to STZ-treated rats exerts hippocampal neuroprotection by restoring myosin-Va expression and the nuclear diameters of pyramidal neurons of the CA3 and the polymorphic cells of the hilus [154]. In a T1D rat model, Garcinia kola seeds limit neuronal loss in regions involved in cognitive and motor functions, including the motor cortex, the medial septal nucleus an cerebellar Purkinje /granular cell layers [155]. Urtica dioica leaves extract also seems to exert it neuroprotective activities by modulating different pathways.…”

An Eluate of the Medicinal Plant Garcinia kola Displays Strong Antidiabetic and Neuroprotective Properties in Streptozotocin-Induced Diabetic Mice

“…The animals were housed in groups of 3 or 4, kept at 23.4°C in a 12/12 h dark-light cycle, with ad libitum access to water and food and permanent video recording aimed at detecting adverse signs or marked behavioral changes. Considering that signs of nervous system involvement are present from the first month post-STZ injection in laboratory rodents [ 25 ], the treatment started two weeks after the STZ injection and lasted two weeks for each of the three phases of the present study (see Section 2.2 ) to avoid unnecessary suffering to the animals.…”

“…In the first series of experiments, the effects of hexane, dichloromethane, ethyl acetate sequential fractions of G. kola extract, and of the remainder (termed as water fraction) were assessed. The mice received doses of fractions equivalent to twice the content in the crude extract's effective dose (100 mg/kg), whose antidiabetic properties were previously reported in other models of diabetic encephalopathy [ 24 , 25 ]. Afterwards, the most active fraction of G. kola was separated using column chromatography.…”

“…We observed that the oral administration of a suspension of G. kola seeds in distilled water or methanolic extract improved the gait and posture of STZ-induced diabetic rats, major indicators of motor function disturbance in this model and in the human disease. These effects were mediated partly by protecting cerebellar neurons from apoptosis and by decreasing neuroinflammation [ 24 , 25 ]. Moreover, we recently reported the ability of G. kola to improve cognitive and motor functions in a rat model of acute radiation syndrome [ 26 – 27 ].…”