School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012 Anhui, China.
Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012 Anhui, China.
J Pharm Pharmacol. 2022 Jan 5;74(1):32-40. doi: 10.1093/jpp/rgab148.
Chrysophanol (CHR), also well-known as Rhei radix et rhizome, is a crucial component in traditional Chinese medicine. It has been widely studied as a potential treatment for many diseases due to its anti-inflammatory effects. However, there are very few studies to establish the potential therapeutic effect of CHR in cell and animal models of Alzheimer's disease (AD). Therefore, we aim to investigate whether CHR could be used as a potential therapeutic approach to patients with AD and further disclose the underlying mechanism. Increasing studies have shown that endoplasmic reticulum (ER) calcium (Ca2+) homeostasis emerges as a central player in AD pathogenesis. Moreover, augmentation of ER stress (ERS) promotes neuronal apoptosis, and excessive oxidative stress is an inducer of ERS. Therefore, we believe that ERS-mediated apoptosis may be one of the causes of AD.
This study examined the neuroprotective effects of CHR on AD rats and AD cell models and explored its potential mechanism.
CHR could reduce the damage of neurons. In AD cell models, CHR significantly inhibited Aβ 25-35-induced neuronal damage, reduced the number of apoptotic cells and improved cell survival rate. Western blot showed that the expression of caspases 3, 9 and 12 was decreased after CHR treatment, and CHR also affected the ERS signalling pathway. In addition, the higher expression of pro-apoptotic proteins in the AD cell model was reduced after CHR treatment by inhibiting GRP78 signalling. Further studies have shown that overexpressed protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) inhibited the regulatory effect of CHR on PERK and weakened the neuroprotective effect of CHR on the AD cell model.
This study revealed a novel mechanism through which CHR plays a neuroprotective role by regulating ERS when it comes to the therapy of AD.
大黄素（CHR），又称大黄根茎，是中药的重要成分。由于其抗炎作用，它已被广泛研究作为许多疾病的潜在治疗方法。然而，在阿尔茨海默病（AD）的细胞和动物模型中，很少有研究确定 CHR 的潜在治疗效果。因此，我们旨在研究 CHR 是否可用于 AD 患者的潜在治疗方法，并进一步揭示其潜在机制。越来越多的研究表明，内质网（ER）钙（Ca2+）稳态成为 AD 发病机制的核心环节。此外，增强 ER 应激（ERS）会促进神经元凋亡，而过度氧化应激是 ERS 的诱导剂。因此，我们认为 ERS 介导的细胞凋亡可能是 AD 的原因之一。
本研究探讨了 CHR 对 AD 大鼠和 AD 细胞模型的神经保护作用及其潜在机制。
CHR 可减轻神经元损伤。在 AD 细胞模型中，CHR 显著抑制 Aβ25-35 诱导的神经元损伤，减少细胞凋亡数量，提高细胞存活率。Western blot 结果显示，CHR 处理后 caspase 3、9 和 12 的表达减少，CHR 还影响 ERS 信号通路。此外，CHR 处理后 AD 细胞模型中促凋亡蛋白的高表达减少，通过抑制 GRP78 信号而减少。进一步的研究表明，过表达蛋白激酶 R（PKR）样内质网激酶（PERK）抑制了 CHR 对 PERK 的调节作用，减弱了 CHR 对 AD 细胞模型的神经保护作用。
本研究揭示了 CHR 通过调节 ERS 发挥神经保护作用的新机制，为 AD 的治疗提供了新的思路。
