The Second Department of Healthcare, China-Japan Friendship Hospital, Beijing, China.
School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, China.
Ann Med. 2024 Dec;56(1):2411011. doi: 10.1080/07853890.2024.2411011. Epub 2024 Oct 11.
Decoction (SHYZD) has exhibited the capacity to enhance cognitive function and learning abilities in individuals diagnosed with Alzheimer's disease (AD) while ameliorating pre-existing neuroinflammation. Nevertheless, the precise mechanism underlying its therapeutic effects on AD remains to be elucidated.
Twenty-four male SAMP8 mice were randomly divided into three groups, and eight male SAMR1 mice were used as a blank control, to examine their learning and spatial memory abilities. The expression of amyloid β1-42 (Aβ1-42) was detected by immunohistochemical staining of hippocampal tissue. ELISA was used to detect the interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) expressions. Real time PCR was used to detect NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteine protease-1 (Caspase-1), and IL-1β mRNA expression. Western blot was used to detect nuclear factor kappa-B (NF-κB), inhibitor of NF-κB α (IκBα), IκB kinase α (IKKα), NLRP3, Caspase-1, and IL-1β protein expression.
In this study, SAMP8 mice, employed as an AD model, displayed markedly diminished abilities in terms of spatial localization, navigation, and spatial exploration when compared to the blank control group. Additionally, there was a substantial upregulation of Aβ1-42 expression in the hippocampus of these mice, along with a significant increase in the levels of inflammation-associated factors, including IL-1β, IL-6, TNF-α, NLRP3, Caspase-1, as well as the NF-κB pathway-related proteins, namely, NF-κB, IκBα, and IKKα. Moreover, after treatment with positive drugs (donepezil hydrochloride) and SHYZD, the learning abilities of the mice exhibited significant improvements. Furthermore, the hallmark AD protein Aβ1-42, inflammatory factors, and NF-κB/NLRP3 signalling pathway proteins were significantly reduced. These findings collectively suggest that SHYZD exerts a therapeutic effect on AD.
In summary, the specific molecular mechanisms through which SHYZD alleviates AD and the potential role for SHYZD in the NF-κB/NLRP3 signalling pathway are identified in this study.
方剂（SHYZD）已表现出增强认知功能和学习能力的能力，在诊断患有阿尔茨海默病（AD）的个体中，同时改善现有的神经炎症。然而，其对 AD 的治疗作用的确切机制仍有待阐明。
将 24 只雄性 SAMP8 小鼠随机分为三组，8 只雄性 SAMR1 小鼠作为空白对照，检测其学习和空间记忆能力。通过海马组织免疫组织化学染色检测淀粉样β 1-42（Aβ1-42）的表达。ELISA 用于检测白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达。实时 PCR 用于检测 NOD 样受体热蛋白结构域相关蛋白 3（NLRP3）、半胱氨酸蛋白酶-1（Caspase-1）和 IL-1β mRNA 表达。Western blot 用于检测核因子 kappa-B（NF-κB）、NF-κBα 抑制剂（IκBα）、IKKα、NLRP3、Caspase-1 和 IL-1β 蛋白表达。
在这项研究中，SAMP8 小鼠作为 AD 模型，与空白对照组相比，空间定位、导航和空间探索能力明显下降。此外，这些小鼠海马区 Aβ1-42 的表达显著上调，炎症相关因子水平显著升高，包括 IL-1β、IL-6、TNF-α、NLRP3、Caspase-1 以及 NF-κB 通路相关蛋白，即 NF-κB、IκBα 和 IKKα。此外，阳性药物（盐酸多奈哌齐）和 SHYZD 治疗后，小鼠的学习能力显著提高。此外，标志性 AD 蛋白 Aβ1-42、炎症因子和 NF-κB/NLRP3 信号通路蛋白显著减少。这些发现共同表明 SHYZD 对 AD 具有治疗作用。
综上所述，本研究确定了 SHYZD 缓解 AD 的具体分子机制以及 SHYZD 在 NF-κB/NLRP3 信号通路中的潜在作用。
