School of Biological Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia; USM-RIKEN International Centre for Ageing Science (URICAS), Universiti Sains Malaysia, 11800, Penang, Malaysia.
School of Biological Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia.
J Ethnopharmacol. 2021 Oct 28;279:114389. doi: 10.1016/j.jep.2021.114389. Epub 2021 Jul 2.
Danshen water extract (DWE), obtained from the Salvia miltiorrhiza Bunge (Family Lamiaceae) root, is usually employed in Chinese traditional medicine as treatment to cardiovascular ailments and cerebrovascular diseases. Intriguingly, the extract was also found to contain vast beneficial properties in Alzheimer's disease (AD) treatment.
Alzheimer's disease is the most significant type of neurodegenerative disorder plaguing societies globally. Its pathogenesis encompasses the hallmark aggregation of amyloid-beta (Aβ). Of all the Aβ oligomers formed in the brain, Aβ42 is the most toxic and aggressive. Despite this, the mechanism behind this disease remains elusive. In this study, DWE, and its major components, Salvianolic acid A (SalA) and Salvianolic acid B (SalB) were tested for their abilities to attenuate Aβ42's toxic effects.
The composition of DWE was determined via Ultra-Performance Liquid Chromatography (UPLC). DWE, SalA and SalB were first verified for their capability to diminish Aβ42 fibrillation using an in vitro activity assay. Since Aβ42 aggregation results in neuronal degeneration, the potential Aβ42 inhibitors were next evaluated on Aβ42-exposed PC12 neuronal cells. The Drosophila melanogaster AD model was then employed to determine the effects of DWE, SalA and SalB.
DWE, SalA and SalB were shown to be able to reduce fibrillation of Aβ42. When tested on PC12 neuronal cells, DWE, SalA and SalB ameliorated cells from cell death associated with Aβ42 exposure. Next, DWE and its components were tested on the Drosophila melanogaster AD model and their rescue effects were further characterized. The UPLC analysis showed that SalA and SalB were present in the brains and bodies of Drosophila after DWE feeding. When human Aβ42 was expressed, the AD Drosophila exhibited degenerated eye structures known as the rough eye phenotype (REP), reduced lifespan and deteriorated locomotor ability. Administration of DWE, SalA and SalB partially reverted the REP, increased the age of AD Drosophila and improved most of the mobility of AD Drosophila.
Collectively, DWE and its components may have therapeutic potential for AD patients and possibly other forms of brain diseases.
丹参水提取物（DWE）来自唇形科丹参（Salvia miltiorrhiza Bunge）的根，通常在中国传统医学中用于治疗心血管疾病和脑血管疾病。有趣的是，该提取物在阿尔茨海默病（AD）治疗中也被发现具有广泛的有益特性。
阿尔茨海默病是全球困扰社会的最主要的神经退行性疾病类型。其发病机制包括淀粉样蛋白-β（Aβ）的标志性聚集。在大脑中形成的所有 Aβ 低聚物中，Aβ42 毒性最强、侵袭性最强。尽管如此，这种疾病的发病机制仍难以捉摸。在这项研究中，DWE 及其主要成分丹酚酸 A（SalA）和丹酚酸 B（SalB）被测试了其减弱 Aβ42 毒性的能力。
通过超高效液相色谱（UPLC）确定 DWE 的组成。首先通过体外活性测定验证 DWE、SalA 和 SalB 降低 Aβ42 纤维形成的能力。由于 Aβ42 聚集导致神经元变性，因此接下来评估潜在的 Aβ42 抑制剂对 Aβ42 暴露的 PC12 神经元细胞的影响。然后使用黑腹果蝇 AD 模型来确定 DWE、SalA 和 SalB 的作用。
DWE、SalA 和 SalB 被证明能够减少 Aβ42 的纤维形成。在 PC12 神经元细胞上进行测试时，DWE、SalA 和 SalB 改善了细胞因暴露于 Aβ42 而死亡的情况。接下来，在黑腹果蝇 AD 模型上测试了 DWE 及其成分，进一步描述了它们的挽救作用。UPLC 分析表明，DWE 喂养后 SalA 和 SalB 存在于果蝇的大脑和身体中。当表达人 Aβ42 时，AD 果蝇表现出退化的眼睛结构，称为粗糙眼睛表型（REP），寿命缩短，运动能力恶化。给予 DWE、SalA 和 SalB 部分逆转了 REP，延长了 AD 果蝇的寿命，并改善了大多数 AD 果蝇的运动能力。
总之，DWE 及其成分可能对 AD 患者和其他形式的脑部疾病具有治疗潜力。
