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Sanguiin H-11 from Sanguisorbae radix protects HT22 murine hippocampal cells against glutamate-induced death
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2018-11-22 , DOI: 10.1016/j.bmcl.2018.11.042
Ji Hoon Song , Song-Yi Kim , Gwi Seo Hwang , Youn-Sub Kim , Hyun Young Kim , Ki Sung Kang

Excessive glutamate level induces neuronal death in acute brain injuries and chronic neurodegenerative diseases. Natural compounds from medicinal and food plants have been attracting interest as a treatment for neurological disorders. Sanguiin H-11 (SH-11), a hydrolysable ellagitannin, inhibits neutrophil movement and nitric oxide -production. However, its neuroprotective effect has not been studied. Therefore, the present study examined the protective effect of SH-11 from Sanguisorbae radix and its mechanism against glutamate-induced death in HT22 cells. Our results showed that SH-11 possessed a strong antioxidant activity and prevented glutamate-induced death in HT22 cells. As a strong antioxidant, SH-11 significantly reduced glutamate-induced increases in intracellular reactive oxygen species accumulation and calcium ion influx. Western blotting analysis showed that glutamate-induced phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-related kinases 1/2, c-Jun N-terminal kinase, and p38, was significantly decreased by SH-11. Furthermore, SH-11 significantly decreased the number of annexin V-positive HT22 cells, which is indicating apoptotic cell death. In conclusion, our results suggested that SH-11 exerted a potent neuroprotective activity against glutamate-mediated apoptotic cell death by inhibiting oxidative stress-mediated MAPK activation.



中文翻译:

Sanguisorbae radix的Sanguiin H-11保护HT22小鼠海马细胞免受谷氨酸诱导的死亡

过量的谷氨酸水平在急性脑损伤和慢性神经退行性疾病中诱导神经元死亡。来自药用和食用植物的天然化合物作为神经系统疾病的治疗方法已引起人们的关注。Sanguiin H-11(SH-11)是可水解的鞣花单宁,可抑制中性粒细胞运动和一氧化氮生成。但是,尚未对其神经保护作用进行研究。因此,本研究探讨了山茱sorb的SH-11的保护作用及其对谷氨酸诱导的HT22细胞死亡的机制。我们的结果表明,SH-11具有很强的抗氧化活性,可防止谷氨酸诱导的HT22细胞死亡。作为一种强大的抗氧化剂,SH-11显着降低了谷氨酸诱导的细胞内活性氧物质积累和钙离子流入的增加。SH-11显着降低了N末端激酶和p38。此外,SH-11明显减少了膜联蛋白V阳性HT22细胞的数量,这表明细胞凋亡。总之,我们的结果表明,SH-11通过抑制氧化应激介导的MAPK活化,对谷氨酸介导的凋亡细胞死亡发挥了有效的神经保护活性。

更新日期:2018-11-22
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