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来自[植物名称未给出]的富含四氢大麻酚的提取物可改善分离的大鼠大脑中的葡萄糖消耗,并调节与神经退行性疾病相关的代谢并发症。

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

作者信息

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

机构信息

Department of Pharmacology, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.

Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa.

出版信息

Front Pharmacol. 2020 Nov 24;11:592981. doi: 10.3389/fphar.2020.592981. eCollection 2020.

DOI:10.3389/fphar.2020.592981
PMID:33390972
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7774498/
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 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. 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. extracts caused a significant ( < 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 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. analysis predicted THC to be permeable across the blood-brain-barrier. THC was also predicted to have an oral LD and toxicity class values of 482 mg/kg and 4 respectively. These results indicate that improves glucose consumption with concomitant suppression of oxidative stress and cholinergic dysfunction, and modulation of purinergic and gluconeogenic activities in brain tissues.

摘要

葡萄糖摄取和利用受损导致的脑葡萄糖消耗减少与神经退行性疾病的发病机制和并发症有关。在离体大鼠脑中研究了富含四氢大麻酚(THC)的提取物刺激脑葡萄糖摄取和利用的能力及其对糖异生、抗氧化、嘌呤能和胆碱能活性的调节作用。依次提取叶子以得到己烷和二氯甲烷提取物。提取物在37℃下与新鲜收获的脑在葡萄糖存在下孵育2小时。对照组为不添加提取物的孵育,而不添加提取物和葡萄糖的脑作为正常对照。二甲双胍用作标准药物。与对照组相比,提取物导致脑葡萄糖摄取显著(<0.05)增加,同时谷胱甘肽水平、超氧化物歧化酶、过氧化氢酶和胞外核苷三磷酸二磷酸水解酶活性升高。用提取物孵育还导致丙二醛和一氧化氮水平、乙酰胆碱酯酶、丁酰胆碱酯酶、葡萄糖6-磷酸酶和果糖-1,6-二磷酸酶活性降低。提取物的气相色谱-质谱分析显示存在THC。分析预测THC可透过血脑屏障。还预测THC的口服半数致死量和毒性等级值分别为482mg/kg和4。这些结果表明,提取物可改善葡萄糖消耗,同时抑制氧化应激和胆碱能功能障碍,并调节脑组织中的嘌呤能和糖异生活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94b7/7774498/1278b6f92e96/fphar-11-592981-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94b7/7774498/bc95b2c3c9a9/fphar-11-592981-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94b7/7774498/1278b6f92e96/fphar-11-592981-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94b7/7774498/669b8e606ed0/fphar-11-592981-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94b7/7774498/90aa7c925dc5/fphar-11-592981-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94b7/7774498/0bf6cca75ea9/fphar-11-592981-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94b7/7774498/ffbd348a91a9/fphar-11-592981-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94b7/7774498/bc95b2c3c9a9/fphar-11-592981-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94b7/7774498/1278b6f92e96/fphar-11-592981-g008.jpg

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