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黄连解毒汤联合多奈哌齐治疗阿尔茨海默病的疗效评价及代谢组学分析。

Efficacy evaluation and metabolomics analysis of Huanglian Jiedu decoction in combination with donepezil for Alzheimer's disease treatment.

机构信息

Department of Geriatrics, The Second Affiliated Hospital of Zhejiang Chinese Medical University, No. 318 Chaowang Road, Hangzhou, Zhejiang 310000, China.

出版信息

J Pharm Biomed Anal. 2023 Oct 25;235:115610. doi: 10.1016/j.jpba.2023.115610. Epub 2023 Jul 29.

DOI:10.1016/j.jpba.2023.115610
PMID:37542831
Abstract

Alzheimer's disease (AD) is a progressive disease with continuous brain changes and has caused a severe burden on families and society. Huanglian Jiedu Decoction (HLJD) is a classic traditional Chinese medicine formula that can improve AD animals' cognitive impairment. This study recruited 50 AD patients who were divided into two groups, one receiving donepezil (DON) treatment and the other receiving DON + HLJD treatment for 3 months. The curative effect, inflammatory and oxidative stress levels were analyzed. The PES-D/11, MMSE, and ADL scales were used to evaluate traditional Chinese medicine syndrome elements, cognitive function, mental state, and life ability. There were no significant differences between the two groups in baseline characteristics and vital sign indicators. After drug treatment, the results showed that AD patients with HLJD combined with DON treatment didn't increase the adverse effects and had good compliance. HLJD combined with DON could improve the disease syndrome, making the differences in PES-D/11, MMSE, and ADL scores before and after the intervention larger. Furthermore, both DON and DON+HLJD treatment inhibited the levels of IL-6, IL-1β, TNF-α, and MDA, raised SOD level, and HLJD enhances the inhibitory effect of DON on inflammation and oxidative stress. IL-6, IL-1β, TNF-α, and MDA levels were significantly correlated with curative effect. Moreover, this study found 107 (206) up-regulated metabolites and 1430 (145) down-regulated metabolites in urine (serum) and conducted differential metabolite screening and correlation analysis suggesting that HLJD may interfere with oxidative stress and inflammation in AD by regulating lipid metabolism and glutamic acid metabolism. Arachidonic acid, diaminopimelic acid, and 1-Aminocyclopropanecarboxylic acid may play an important role in HLJD to improve AD.

摘要

阿尔茨海默病(AD)是一种进行性疾病,其大脑会持续发生变化,给家庭和社会带来了严重负担。黄连解毒汤(HLJD)是一种经典的中药方剂,可改善 AD 动物的认知障碍。本研究招募了 50 名 AD 患者,将其分为两组,一组接受多奈哌齐(DON)治疗,另一组接受 DON+HLJD 治疗 3 个月。分析疗效、炎症和氧化应激水平。采用 PES-D/11、MMSE 和 ADL 量表评估中医证候要素、认知功能、精神状态和生活能力。两组患者在基线特征和生命体征指标方面无显著差异。经过药物治疗,结果表明,HLJD 联合 DON 治疗不会增加不良反应,且患者依从性较好。HLJD 联合 DON 可改善疾病证候,使 PES-D/11、MMSE 和 ADL 评分在干预前后的差异更大。此外,DON 和 DON+HLJD 治疗均抑制了 IL-6、IL-1β、TNF-α 和 MDA 水平,提高了 SOD 水平,HLJD 增强了 DON 对炎症和氧化应激的抑制作用。IL-6、IL-1β、TNF-α 和 MDA 水平与疗效显著相关。此外,本研究在尿液(血清)中发现了 107(206)个上调代谢物和 1430(145)个下调代谢物,并进行了差异代谢物筛选和相关性分析,表明 HLJD 可能通过调节脂代谢和谷氨酸代谢来干预 AD 中的氧化应激和炎症。花生四烯酸、二氨基庚二酸和 1-氨基环丙烷羧酸可能在 HLJD 改善 AD 中发挥重要作用。

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