Andrographolide restores glucose uptake in rat hippocampal neurons,Journal of Neurochemistry

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Andrographolide restores glucose uptake in rat hippocampal neurons
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2020-10-30 , DOI: 10.1111/jnc.15229
Camila Gherardelli ₁ , Pedro Cisternas ₁ , Joel Gutiérrez ₁ , Milka Martinez ₁ , Nibaldo C Inestrosa _{1,

2}

Affiliation

Cerebral glucose hypometabolism is a common pathophysiological characteristic of many neurodegenerative diseases. This metabolic dysfunction includes alterations in glucose transport from the blood into the neurons by the facilitative glucose transporters (GLUTs). Several studies suggest that metabolic disturbances precede clinical symptoms and correlate with disease progression. Some groups have started to explore the use of therapeutic strategies that target decreased cerebral glucose metabolism to promote its availability. We selected Andrographolide (Andro), a natural product obtained from Andrographis paniculate that has both anti-hyperglycemic and anti-diabetic effects. Although it was shown to promote glucose uptake in vivo, the underlying mechanisms remain unclear. Here, we evaluated the acute effects of Andro on glucose transport and metabolism using primary rat hippocampal neuronal cultures. Our results showed that Andro enhances neuronal glucose uptake and stimulates glucose metabolism by inducing GLUT3 and 4 expression in neurons, as well as by promoting glycolysis. We also observed that Andro-mediated effects depend on the activity of AMP-activated protein kinase (AMPK), one of the central regulators of glucose metabolism. Our studies open the possibility to use Andro as a drug to restore glucose levels in neurodegenerative diseases.

中文翻译：

穿心莲内酯可恢复大鼠海马神经元的葡萄糖摄取

脑葡萄糖代谢低下是许多神经退行性疾病的常见病理生理特征。这种代谢功能障碍包括通过促进性葡萄糖转运蛋白（GLUT）从血液到神经元的葡萄糖转运发生改变。多项研究表明，代谢紊乱先于临床症状，并与疾病进展相关。一些小组已经开始探索针对减少脑葡萄糖代谢以促进其可用性的治疗策略的使用。我们选择了穿心莲内酯（Andro），它是从穿心莲中提取的天然产物。具有降血糖和抗糖尿病作用。尽管已表明它可以促进体内葡萄糖的吸收，但其潜在机制仍不清楚。在这里，我们使用原代大鼠海马神经元培养物评估了Andro对葡萄糖转运和代谢的急性作用。我们的结果表明，Andro通过诱导神经元中GLUT3和4的表达以及促进糖酵解，增强神经元葡萄糖的摄取并刺激葡萄糖的代谢。我们还观察到，Andro介导的作用取决于AMP激活的蛋白激酶（AMPK）（葡萄糖代谢的中心调节剂之一）的活性。我们的研究开辟了使用安德罗作为药物来恢复神经退行性疾病中葡萄糖水平的可能性。

更新日期：2020-10-30

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