Vattanarongkup Jaturavit, Piyachaturawat Pawinee, Tuchinda Patoomratana, Sanvarinda Pimtip, Sanvarinda Yupin, Jantaratnotai Nattinee
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Planta Med. 2016 Nov;82(17):1456-1462. doi: 10.1055/s-0042-109173. Epub 2016 Jun 24.
Oxidative stress is one of the major mechanisms causing neuronal and astroglial cell death in various neurological disorders such as Alzheimer's disease, Parkinson's disease, and brain ischemia. Two diarylheptanoids, (3)-1,7-diphenyl-(4,6)-4,6-heptadien-3-ol (ASPP 049) and (3)-7-(3,4-dihydroxyphenyl)-1-phenyl-(1)-1-hepten-3-ol (ASPP 092), isolated from were investigated for cytoprotective effects on C6 astroglial cells using hydrogen peroxide (HO) exposure as a model of oxidative stress. ASPP 092 demonstrated free radical scavenging activity comparable to that of vitamin C, while ASPP 049 showed no antioxidant activity. Treatment with HO at 400 µM for 12 h caused 79 % C6 astroglial cell death which was significantly reduced to 37 % by pretreatment with ASPP 092 (5 µM). In addition, ASPP 092 attenuated the increase in reactive oxygen species production and the decrease in total glutathione level induced by HO. The mechanism of ASPP 092 protection against HO-induced apoptotic signaling appeared to involve prevention of increase in the level of phosphorylated p53 and the Bax/Bcl-2 ratio as well as cleaved caspase-3. These findings provide new evidence that the diarylheptanoid ASPP 092 from possesses antiapoptotic properties and could be further developed as a potential treatment for oxidative stress-related neuronal diseases.
氧化应激是导致各种神经疾病（如阿尔茨海默病、帕金森病和脑缺血）中神经元和星形胶质细胞死亡的主要机制之一。从[具体来源未给出]中分离出的两种二芳基庚烷类化合物，(3)-1,7-二苯基-(4,6)-4,6-庚二烯-3-醇（ASPP 049）和(3)-7-(3,4-二羟基苯基)-1-苯基-(1)-1-庚烯-3-醇（ASPP 092），以过氧化氢（HO）暴露作为氧化应激模型，研究了它们对C6星形胶质细胞的细胞保护作用。ASPP 092表现出与维生素C相当的自由基清除活性，而ASPP 049则没有抗氧化活性。用400 µM的HO处理12小时导致79%的C6星形胶质细胞死亡，而用ASPP 092（5 µM）预处理可将其显著降低至37%。此外，ASPP 092减弱了HO诱导的活性氧生成增加和总谷胱甘肽水平降低。ASPP 092对HO诱导的凋亡信号的保护机制似乎涉及防止磷酸化p53水平、Bax/Bcl-2比率以及裂解的caspase-3的增加。这些发现提供了新的证据，表明来自[具体来源未给出]的二芳基庚烷类化合物ASPP 092具有抗凋亡特性，可进一步开发作为氧化应激相关神经疾病的潜在治疗药物。
