School of Pharmacy, Lanzhou University, Donggang Road No. 199, Lanzhou, 730000, China.
School of Pharmacy, Lanzhou University, Donggang Road No. 199, Lanzhou, 730000, China.
J Ethnopharmacol. 2021 Mar 25;268:113640. doi: 10.1016/j.jep.2020.113640. Epub 2020 Dec 8.
Terminalia chebula Retz. (T.chebula) is an important medicinal plant in Tibetan medicine and Ayurveda. T.chebula is known as the "King of Tibetan Medicine", due to its widespread clinical pharmacological activity such as anti-inflammatory, antioxidative, antidiabetic as well as anticancer in lots of in vivo and in vitro models. In this study, we use transgenic and/or RNAi Caenorhabditis elegans (C.elegans) model to simulation the AD pathological features induced by Aβ, to detect the effect of TWE on improving Aβ-induced toxicity and the corresponding molecular mechanism.
The study aimed to tested the activities and its possible mechanism of T.chebula to against Aβ induced toxicity and Aβ aggregation.
Using transgenic C.elegans strain CL2006 and CL4176 as models respond to paralytic induced by Aβ toxicity. The transcription factors DAF-16 and SKN-1 were analyzed used a fluorescence microscope in transgenic strains (DAF-16:GFP, SKN-1:GFP). The function of DAF-16 and SKN-1 was further investigated using loss-of-function strains by feeding RNA interference (RNAi) bacteria. To evaluate the aggregation level of Aβ in the transgenic C.elegans, Thioflavin S (ThS) staining and WB visualized the levels of Aβ monomers and oligomers.
TWE treatment can significantly improve the paralysis of transgenic C.elegans caused by Aβ aggregation (up to 14%). The Aβ aggregates in transgenic C.elegans are significantly inhibited under TWE exposure (up to 70%). TWE increases the nuclear localization of the key transcription factor DAF-16 and HSF-1, which in turn leads to the expression of downstream Hsp-16.2 protein and exerts its inhibitory effect on Aβ aggregation. Meanwhile, paralysis improved has not observed in SKN-1 mutation and/or RNAi C.elegans.
Our results indicate that TWE can protect C.elegans against the Aβ-induced toxicity, inhibition Aβ aggregation and delaying Aβ-induced paralysis. The neuroprotective effect of TWE involves the activation of DAF-16/HSF-1/Hsp-16.2 pathway.
诃子（Terminalia chebula Retz.）是藏药和阿育吠陀中的一种重要药用植物。由于其在许多体内和体外模型中具有广泛的临床药理学活性，如抗炎、抗氧化、抗糖尿病和抗癌作用，诃子被称为“藏药之王”。在这项研究中，我们使用转基因和/或 RNAi 秀丽隐杆线虫（C.elegans）模型来模拟 Aβ 诱导的 AD 病理特征，以检测 TWE 改善 Aβ 诱导的毒性的作用及其相应的分子机制。
本研究旨在测试诃子对 Aβ 诱导的毒性和 Aβ 聚集的作用及其可能的机制。
使用转基因 C.elegans 株系 CL2006 和 CL4176 作为模型，以响应 Aβ 毒性诱导的瘫痪。在转基因株系（DAF-16:GFP、SKN-1:GFP）中使用荧光显微镜分析转录因子 DAF-16 和 SKN-1。通过喂食 RNA 干扰（RNAi）细菌进一步研究 DAF-16 和 SKN-1 的功能。为了评估转基因 C.elegans 中 Aβ 的聚集水平，使用噻唑蓝 S（ThS）染色和 WB 可视化 Aβ 单体和寡聚物的水平。
TWE 处理可显著改善 Aβ 聚集诱导的转基因 C.elegans 的瘫痪（高达 14%）。在 TWE 暴露下，Aβ 聚集在转基因 C.elegans 中显著受到抑制（高达 70%）。TWE 增加了关键转录因子 DAF-16 和 HSF-1 的核定位，进而导致下游 Hsp-16.2 蛋白的表达，并发挥其对 Aβ 聚集的抑制作用。同时，在 SKN-1 突变和/或 RNAi C.elegans 中未观察到瘫痪的改善。
我们的结果表明，TWE 可以保护 C.elegans 免受 Aβ 诱导的毒性、抑制 Aβ 聚集和延缓 Aβ 诱导的瘫痪。TWE 的神经保护作用涉及 DAF-16/HSF-1/Hsp-16.2 通路的激活。
