Li Liangdong, Xue Jinhua, Liu Ruizhen, Li Xiao, Lai Lijuan, Xie Jiali, Huang Zhihua, Huang Cheng
Institute for Medical Sciences of Pain, Department of Physiology, School of Basic Medical Sciences, Gannan Medical University, Yi Xue Yuan Load, Ganzhou 341000, Jiangxi, PR China.
Department of Physiology, School of Basic Medical Sciences, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
Neurosci Lett. 2017 Apr 12;646:43-48. doi: 10.1016/j.neulet.2017.02.046. Epub 2017 Feb 22.
In order to improve the poor water solubility of genistein (4',5,7-trihydroxyisoflavone), which is extracted from food sources such as tofu, soybeans, and kudzu, we sulfonated genistein to synthesize a relatively more water-soluble compound, namely genistein-3'-sodium sulfonate (GSS). Our previous studies demonstrate that GSS protects cortical neurons from injury induced by focal cerebral ischemia. However, the molecular mechanisms underlying this protective effect remain unclear. We aimed to investigate the protective effect and potential molecular mechanisms of action of GSS in rat glutamate-induced cortical neuron injury in vitro and middle cerebral artery occlusion (MCAO) in vivo models. Our results showed that GSS exhibited a protective effect against glutamate-induced cytotoxicity in rat cortical neurons by reducing lactate dehydrogenase (LDH) release, inhibiting cell apoptosis, increasing Bcl-2/Bax expression ratio, and reducing Caspase 3 activity. GSS also decreased the infarcted area and neurological deficits in the rat MCAO model, reduced LDH release from the brain tissue to the serum, increased the Bcl-2/Bax expression ratio, and reduced Caspase 3 activity. These findings suggest that GSS protects rat cortical neurons from injury induced by focal cerebral ischemia in both in vitro and in vivo models, through increased Bcl-2/Bax expression ratio and reduced Caspase 3 activity.
为了改善从豆腐、大豆和葛根等食物来源中提取的染料木黄酮（4',5,7-三羟基异黄酮）较差的水溶性，我们对染料木黄酮进行磺化，以合成一种水溶性相对更高的化合物，即染料木黄酮-3'-磺酸钠（GSS）。我们之前的研究表明，GSS可保护皮质神经元免受局灶性脑缺血诱导的损伤。然而，这种保护作用背后的分子机制仍不清楚。我们旨在研究GSS在体外大鼠谷氨酸诱导的皮质神经元损伤和体内大脑中动脉闭塞（MCAO）模型中的保护作用及潜在的分子作用机制。我们的结果表明，GSS通过减少乳酸脱氢酶（LDH）释放、抑制细胞凋亡、增加Bcl-2/Bax表达比率以及降低Caspase 3活性，对大鼠皮质神经元谷氨酸诱导的细胞毒性表现出保护作用。GSS还可减少大鼠MCAO模型中的梗死面积和神经功能缺损，减少脑组织向血清中的LDH释放，增加Bcl-2/Bax表达比率，并降低Caspase 3活性。这些发现表明，GSS在体外和体内模型中均可通过增加Bcl-2/Bax表达比率和降低Caspase 3活性，保护大鼠皮质神经元免受局灶性脑缺血诱导的损伤。
