Tetrahydrocannabinol-Rich Extracts From Cannabis Sativa L. Improve Glucose Consumption and Modulate Metabolic Complications Linked to Neurodegenerative Diseases in Isolated Rat Brains.

Ochuko L Erukainure,Veronica F Salau,Md Shahidul Islam,Motlalepula G Matsabisa

doi:10.3389/fphar.2020.592981

Ochuko L Erukainure, Veronica F Salau + Show 2 more

Open Access

https://doi.org/10.3389/fphar.2020.592981

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Abstract

Reduced brain glucose consumption arising from impaired glucose uptake and utilization has been linked to the pathogenesis and complications of neurodegenerative diseases. The ability of Cannabis sativa L. tetrahydrocannabinol (THC)-rich extracts to stimulate brain glucose uptake and utilization as well as its modulatory effect on gluconeogenesis, antioxidative, purinergic and cholinergic activities were investigated in isolated rats’ brains. C. sativa leaves were sequentially extracted to yield the hexane and dichloromethane extracts. The extracts were incubated at 37°C with freshly harvested brains in the presence of glucose for 2 h. The control consisted of incubation without the extracts, while brains without the extracts and glucose served as the normal control. Metformin was used as the standard drug. C. sativa extracts caused a significant (p < 0.05) increase in brain glucose uptake, with concomitant elevation of glutathione level, superoxide dismutase, catalase, and ecto-nucleoside triphosphate diphosphohydrolase activities compared to the controls. Incubation with C. sativa extracts also led to depletion in malondialdehyde and nitric oxide levels, acetylcholinesterase, butyrylcholinesterase, glucose 6-phosphatase and fructose-1,6-biphosphatase activities. GC-MS analysis of the extracts revealed the presence of THC. In silico analysis predicted THC to be permeable across the blood-brain-barrier. THC was also predicted to have an oral LD50 and toxicity class values of 482 mg/kg and 4 respectively. These results indicate that C. sativa improves glucose consumption with concomitant suppression of oxidative stress and cholinergic dysfunction, and modulation of purinergic and gluconeogenic activities in brain tissues

Highlights

The brain’s dependence on glucose for energy generation is well documented
Glucose transporters aid in transporting glucose across the blood brain barrier (BBB) from the blood stream to the brain
Incubation of brain tissues with glucose in the presence of hexane and DCM extracts of C. sativa leaves led to significant (p < 0.05)

Summary

Introduction

The brain’s dependence on glucose for energy generation is well documented. Brain glucose homeostasis has been reported to be important for neuronal generation and maintenance, regulation of neurotransmitter, cognitive function and synaptic plasticity (Neumann et al, 2008). Altered glucose homeostasis in the central nervous system (CNS) has been reported in most neurodegenerative diseases such as Alzheimer’s and Parkinson diseases (An et al, 2018). This has been attributed to abnormalities in insulin signaling pathways in the brain as well as alteration of the glucose transporters at the BBB (Gejl et al, 2017; An et al, 2018). Making the brain susceptible to degenerative diseases This is evident in studies which correlated the risk of Alzheimer’s disease with reduced brain glucose metabolism (Duran-Aniotz and Hetz, 2016)

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