Background: Recent evidences suggest that cerebellar degeneration may be associated with the development of Alzheimer's disease (AD). However, previous reports were mainly observational, lacking substantial characterization of cellular and molecular cerebellar features during AD progression. Purpose: This study is aimed at characterizing the cerebellum in rat models of AD and assessing the corresponding neuroprotective mechanisms of Garcinia biflavonoid complex (GBc). Methods: Male Wistar rats were grouped and treated alone or in combination with PBS (ad libitum)/day, corn oil (CO; 2 mL/kgBw/day), GBc (200 mg/kgBw/day), sodium azide (NaN3) (15 mg/kgBw/day) and aluminium chloride (AlCl3) (100 mg/kgBw/day). Groups A and B received PBS and CO, respectively; C received GBc; D received NaN3; E received AlCl3; F received NaN3 then GBc subsequently; G received AlCl3 then GBc subsequently; H received NaN3 and GBc simultaneously while I received AlCl3 and GBc simultaneously. Following treatments, cerebellar cortices were processed for histology, immunohistochemistry and colorimetric assays. Results: Our data revealed that cryptic granule neurons and pyknotic Purkinje cell bodies (characterized by short dendritic/axonal processes) correspond to indistinctly demarcated cerebellar layers in rats treated with AlCl3 and NaN3. These correlates, with observed hypertrophic astrogliosis, increased the neurofilament deposition, depleted the antioxidant system-shown by expressed superoxide dismutase and glutathione peroxidase, and cerebellar glucose bioenergetics dysfunction-exhibited in assayed lactate dehydrogenase and glucose-6-phosphate dehydrogenase. We further showed that GBc reverses cerebellar degeneration through modulation of neurochemical signaling pathways and stressor molecules that underlie AD pathogenesis. Conclusion: Cellular, molecular and metabolic neurodegeneration within the cerebellum is associated with AlCl3 and NaN3-induced AD while GBc significantly inhibits corresponding neurotoxicity and is more efficacious when pre-administered.
The antidiabetic, normolipidaemic, antioxidant and safety evaluations of ethanolic extract of Acacia ataxacantha roots (EEAAR) were investigated in streptozotocin -induced diabetic rats, to verify its use in traditional African medicine and as alternative to synthetic normoglycaemic agents in diabetic treatments. Thirty albino rats (Rattus novergicus) were randomized into six groups -control, diabetic control, EEAAR-treated at 125 mg/kg, 250 mg/kg, 500 mg/kg body weights (b.wts.) and metformin groups, respectively. Phytochemical screening showed the presence of alkaloids, polyphenols, flavonoid, saponins, tannins and terpenoid. Blood glucose was significantly reduced (p < 0.05) especially after 7 days of oral administration of EEAAR at 125 mg/kg b.wt with values (110.01 ± 9.64 mg/dl) similar to that of the control (106.33 ± 4.13 mg/dl). There was an increase (p < 0.05) in the ALT and AST activities of the liver and serum of rats in all the groups except in those that received 125 mg/kg b.wt. Serum total cholesterol, low density lipoprotein cholesterol and triglyceride were decreased (p < 0.05) upon administration of the extract and metformin. There was no difference (p > 0.05) in malondialdehyde concentration of rats administered with 125 mg/kg b.wt. of extract and metformin. Superoxide dismutase activity was elevated (p < 0.05) in all groups and compared favourably with the control in each of the tissues. This study revealed the antidiabetic and hypolipidaemic effects of EEAAR, which may be due to the antioxidant properties of some of the phytochemical constituents. However, the extract may not be safe at large and repeated doses.
Author TCA designed the study, performed the statistical analysis, wrote the protocol, and wrote the first draft of the manuscript. Authors ROA and OJO managed the analyses of the study. Author ITI managed the literature searches. All authors read and approved the final manuscript.
The antidiabetic, normolipidaemic, antioxidant and safety evaluations of ethanolic extract of Acacia ataxacantha roots (EEAAR) were investigated in streptozotocin - induced diabetic rats, to verify its use in traditional African medicine and as alternative to synthetic normoglycaemic agents in diabetic treatments. Thirty albino rats (Rattus novergicus) were randomized into six groups - control, diabetic control, EEAAR-treated at 125 mg/kg, 250 mg/kg, 500 mg/kg body weights (b.wts.) and metformin groups, respectively. Phytochemical screening showed the presence of alkaloids, polyphenols, flavonoid, saponins, tannins and terpenoid. Blood glucose was significantly reduced (p < 0.05) especially after 7 days of oral administration of EEAAR at 125 mg/kg b.wt with values (110.01 ± 9.64 mg/dl) similar to that of the control (106.33 ± 4.13 mg/dl). There was an increase (p < 0.05) in the ALT and AST activities of the liver and serum of rats in all the groups except in those that received 125 mg/kg b.wt. Serum total cholesterol, low density lipoprotein cholesterol and triglyceride were decreased (p < 0.05) upon administration of the extract and metformin. There was no difference (p > 0.05) in malondialdehyde concentration of rats administered with 125 mg/kg b.wt. of extract and metformin. Superoxide dismutase activity was elevated (p < 0.05) in all groups and compared favourably with the control in each of the tissues. This study revealed the antidiabetic and hypolipidaemic effects of EEAAR, which may be due to the antioxidant properties of some of the phytochemical constituents. However, the extract may not be safe at large and repeated doses.
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