Icariin Protects SH-SY5Y Cells from Formaldehyde-Induced Injury through Suppression of Tau Phosphorylation

Objective: To investigate the neuroprotective effects of icariin on formaldehyde(FA)-treated human neuroblastoma SH-SY5Y cells and the possible mechanisms involved. Methods: SH-SY5Y cells were divided into FA treatment group, FA treatment group with icariin, and the control group. Cell viability, apoptosis, and morphological changes were determined by cell counting kit-8(CCK8), flow cytometry, and confocal microscopy, respectively. The phosphorylation of Tau protein was examined by western blotting. Results: FA showed a half lethal dose(LD50) of 0.3 mmol/L in SH-SY5Y cells under the experimental conditions. Icariin(1–10 μmol/L) prevented FA-induced cell death in SH-SY5 Y cells in a dose-dependent manner, with the optimal effect observed at 5 μmol/L. After FA treatment, the absorbance in FA group was 1.31±0.05, while in the group of icariin(5 μmol/L) was 1.63±0.05. Examination of cell morphology by confocal microscopy demonstrated that 5 μmol/L icariin significantly attenuated FA-induced cell injury(P0.05). Additionally, Icariin inhibited FA-induced cell apoptosis in SH-SY5 Y cells. Results from western blotting showed that icariin suppressed FA-induced phosphorylation at Thr 181 and Ser 396 of Tau protein, while having no effect on the expression of the total Tau protein level. Furthermore, FA activated Tau kinase glycogen synthase kinase 3 beta(GSK-3β) by enhancement of Y216 phosphorylation, but icariin reduced Y216 phosphorylation and increased Ser 9 phosphorylation. Conclusion: Icariin protects SH-SY5Y cells from FA-induced injury possibly through the inhibition of GSK-3β-mediated Tau phosphorylation.     

慢性脱水与老年认知损伤及饮水干预

老年认知损伤被认为是一个病理生理学的连续发展过程,包括轻度认知损伤前期（pre-mild cognitive impairment, pre-MCI）、轻度认知损伤（mild cognitive impairment, MCI）、老年性痴呆（Alzheimer’s disease, AD）三个阶段。慢性脱水是老年性痴呆患者共同具有的一种特征。红外线摄像监控C57 BL/6小鼠饮水频率和饮水量的结果显示,老龄鼠的饮水频率（P<0.05）和饮水量（P<0.01）均较年轻对照组显著减少。一方面,认知损伤患者“口渴”的感受降低、记忆能力减退,被认为是造成老年慢性脱水的原因;脱水引起脑内细胞毒性代谢物,如内源甲醛等增加、积累,加重认知损伤,形成“脱水¾认知损伤¾脱水”的恶性循环。另一方面,体内甲醛浓度随老龄化（>65岁）而逐渐升高,且AD病人脑内甲醛含量也显著升高。研究表明,合理饮水不但可以改善老龄化人群的慢性脱水状态,同时能够明显降低体内的甲醛浓度,防止甲醛过量对中枢神经系统的危害。甲醛代谢失调所造成的中枢神经系统慢性损伤,被认为是老年认知损伤的原因之一。因此,合理饮水习惯的建立,被认为是减缓中老年人慢性脱水和体内细胞毒性代谢产物累积的方法之一,也可能在某种程度上,起到干预老年认知损伤早期发生发展的效果。     

二氢乳清酸脱氢酶抑制剂在抗疟疾领域的研究进展

二氢乳清酸脱氢酶(DHODH)是核酸中嘧啶合成的关键酶,而疟原虫嘧啶补救途径的缺失,使得从头生物合成途径成为疟原虫获得生长所需嘧啶的唯一来源.显然,DHODH可作为抗疟药的潜在作用靶点,对新药的研发具有重要意义.通过药物化学家的不断努力,目前已得到若干潜在的恶性疟原虫二氢乳清酸脱氢酶(PfDHODH)抑制剂.特别值得一提的是,DSM265(5)具有良好的体内外活性、药代动力学性质且体内安全性,是第一个处于临床研究阶段的PfDHODH抑制剂,值得期待.本文归纳了近年来DHODH抑制剂在抗疟疾领域的研究进展,并讨论了构效关系,为寻找新的抗疟药提供帮助.     

靛红类化合物的抗疟疾活性

疟疾是全球性传染病,每年约有5亿人罹患疟疾,死亡近百万.尽管临床上使用的抗疟药物对药敏型疟疾疗效显著,但是耐药疟原虫的出现使得这类药物的疗效逐年下降.因此,有必要研发新型抗疟药.靛红具有多种生物活性,广泛存在于药物分子中.近年来的研究表明,靛红类化合物具有潜在的抗疟疾活性,引起了药物化学家的极大兴趣.本文将归纳近年来靛红类化合物在抗疟疾领域的研究进展,并讨论这类化合物的构-效关系,为更合理的设计抗疟新药提供理论帮助.