Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Lanzhou, P.R. China.
Sci Rep. 2017 Sep 12;7(1):11408. doi: 10.1038/s41598-017-11628-9.
Dianxianning (DXN) is a traditional Chinese formula, and has been approved in China for treating epilepsy since 1996. Here anti-Alzheimer's disease activity of DXN has been reported. DXN improved AD-like symptoms of paralysis and 5-HT sensitivity of transgenic Aβ C. elegans. In worms, DXN significantly increased Aβ monomers and decreased the toxic Aβ oligomers, thus reducing Aβ toxicity. DXN significantly suppressed the expression of hsp-16.2 induced by juglone, and up-regulated sod-3 expression. These results indicated that DXN increased stress resistance and protected C. elegans against oxidative stress. Furthermore, DXN could significantly promote DAF-16 nuclear translocation, but it did not activate SKN-1. The inhibitory effect of DXN on the Aβ toxicity was significantly reverted by daf-16 RNAi, rather than skn-1 RNAi or hsf-1 RNAi. These results indicated that DAF-16 is at least partially required for the anti-AD effect of DXN. In conclusion, DXN improved Aβ-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic worms. Together with our data obtained by Morris water maze test, the results showed that DXN markedly ameliorated cognitive performance impairment induced by scopolamine in mice. All the results support that DXN is a potential drug candidate to treat Alzheimer's diseases.
滇仙鹤(DXN)是一种中药配方,自 1996 年以来已在中国获准用于治疗癫痫。在这里报告了 DXN 的抗阿尔茨海默病(AD)活性。DXN 改善了瘫痪的 AD 样症状和转基因 Aβ C. elegans 对 5-HT 的敏感性。在蠕虫中,DXN 显著增加了 Aβ单体并减少了有毒的 Aβ寡聚物,从而降低了 Aβ毒性。DXN 显著抑制了 Juglone 诱导的 hsp-16.2 的表达,并上调了 sod-3 的表达。这些结果表明 DXN 增加了应激抗性并保护 C. elegans 免受氧化应激。此外,DXN 可显著促进 DAF-16 的核易位,但不会激活 SKN-1。DAF-16 RNAi 可显著逆转 DXN 对 Aβ毒性的抑制作用,而 skn-1 RNAi 或 hsf-1 RNAi 则不能。这些结果表明 DAF-16 至少部分参与了 DXN 的抗 AD 作用。总之,DXN 通过转基因蠕虫中的 DAF-2/DAF-16 胰岛素样途径部分改善了 Aβ 诱导的病理特征。结合我们通过 Morris 水迷宫试验获得的数据,结果表明 DXN 显著改善了东莨菪碱诱导的小鼠认知功能障碍。所有结果均支持 DXN 是治疗阿尔茨海默病的潜在药物候选物。