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揭示 Lobaria 提取物及其缩酚酸/缩酚酮在对抗阿尔茨海默病中 Aβ42 肽聚集和神经毒性方面的治疗潜力。

Unveiling the therapeutic potential of Lobaria extract and its depsides/depsidones in combatting Aβ42 peptides aggregation and neurotoxicity in Alzheimer's disease.

发表日期:2024
作者: Meixia Yang, Caishan Yan, Dusadee Ospondpant, Lisong Wang, Shengying Lin, Wai Lun Tang, Tina Tingxia Dong, Penger Tong, Qin Xu, Karl Wah Keung Tsim
来源: Frontiers in Pharmacology

摘要:

背景:开发能够抑制β淀粉样蛋白(Aβ)肽聚集并促进神经突生长的有效抑制剂对于阿尔茨海默病(AD)的可能治疗至关重要。 Lobaria (Schreb.) Hoffm. 是一种在喜马拉雅地区用于治疗炎症性疾病的中药,含有缩酚酸/缩酚酮 (DEP),例如鹿角酸、norstictic Acid 和 stictic Acid,因其抗癌和抗炎特性而闻名。方法:使用 HPLC 分析 Lobaria 提取物,以鉴定 DEP 并建立标准。使用生物物理和细胞方法的各种方法评估了 Lobaria 对 Aβ42 纤维化和解聚的抑制作用。还评估了 Lobaria 提取物的神经保护活性及其对抗 Aβ 介导的细胞毒性的 DEP。结果:洛巴利亚水提物中检出北穗花胶和穗花酸,乙醇提取物中检出北穗花胶、穗花酸和旋花酸。两种提取物及其 DEP 均能有效抑制 Aβ42 纤维颤动并分解成熟的 Aβ42 纤维。值得注意的是,与水提取物相比,乙醇提取物显示出优异的抑制效果,其中旋转酸是最有效的 DEP。此外,草药提取物处理的 Aβ42 聚集物质显着保护神经元细胞免受 Aβ42 诱导的细胞损伤,并促进神经突生长。结论:本研究首次探讨了 Lobaria 对 AD 中 Aβ42 和神经元细胞的影响。鉴于 Lobaria 常用于民族医药和食品并具有良好的安全记录,我们的研究结果表明 Lobaria 提取物和 DEP 有潜力作为 AD 患者的神经保护和治疗药物。版权所有 © 2024 Yang, Yan, Ospondpant, Wang, Lin, Tang,董、童、徐和詹。
Background: The development of effective inhibitors that can inhibit amyloid β (Aβ) peptides aggregation and promote neurite outgrowth is crucial for the possible treatment of Alzheimer's disease (AD). Lobaria (Schreb.) Hoffm., a traditional Chinese medicine used in Himalaya region for inflammatory diseases, contains depsides/depsidones (DEPs) such as gyrophoric acid, norstictic acid, and stictic acid known for their anti-cancer and anti-inflammation properties. Methods: Lobaria extracts were analyzed using HPLC to identify DEPs and establish standards. The inhibitory effects of Lobaria on Aβ42 fibrillization and depolymerization were assessed using various approaches with biophysical and cellular methods. The neuroprotective activity of Lobaria extracts and its DEPs aganist Aβ-mediated cytotoxicity was also evaluated. Results: Norstictic and stictic acid were found in the water extract, while norstictic, stictic, and gyrophoric acid were detected in the ethanol extract of Lobaria. Both extracts, and their DEPs effectively inhibited Aβ42 fibrillation and disaggregate mature Aβ42 fibrils. Notably, the ethanol extract showed superior inhibitory effect compared to the water extract, with gyrophoric acid being the most effective DEPs. Additionally, herbal extract-treated Aβ42 aggregation species significantly protected neuronal cells from Aβ42-induced cell damage and promoted neurite outgrowth. Conclusion: This study is the first to investigate the effect of Lobaria on Aβ42 and neuronal cell in AD. Given that Lobaria is commonly used in ethnic medicine and food with good safety records, our findings propose that Lobaria extracts and DEPs have potential as neuroprotective and therapeutic agents for AD patients.Copyright © 2024 Yang, Yan, Ospondpant, Wang, Lin, Tang, Dong, Tong, Xu and Tsim.