Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM and Engineering & Technology Research Center for Chinese Materia Medica Quality of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, PR China.
J Pharm Biomed Anal. 2021 Jan 5;192:113652. doi: 10.1016/j.jpba.2020.113652. Epub 2020 Sep 28.
Diabetic encephalopathy (DE) is a severe diabetic complication with cognitive dysfunction. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese formula, is effective for the treatment of diabetes mellitus and Alzheimer's disease in clinical practices, however, the therapeutic effects and the underlying mechanisms of HLJDD on DE is unclear yet. With this purpose, behavior test, brain histological and biochemical analysis were estimated to assess the beneficial effects of HLJDD on DE. Plasma samples were collected for metabolomics analysis based on UPLC-Q-Orbitrap HRMS/MS and chemometric analysis. As a result, morris water maze test revealed that HLJDD could effectively improve the learning and memory abilities in db/db mice. Brain histological and biochemical analysis indicated that HLJDD could protect against neurodegeneration and oxidative stress in db/db mice. Meanwhile, a total of 21 potential biomarkers with significant differences were identified between Model group and Control group using untargeted metabolomics strategy. Among them, 11 metabolites showed a trend towards the normal levels after HLJDD intervention. These metabolites principally involved in glycerophospholipid metabolism, fatty acid β-oxidation, linoleic acid metabolism, glucose metabolism and glutathione metabolism based on the metabolic pathway analysis, which were regulated in DE model mice after HLJDD intervention. Generally, the results demonstrated that HLJDD had beneficial effects on DE, which could be mediated via ameliorating the metabolic disorders.
糖尿病脑病（DE）是一种严重的糖尿病并发症，伴有认知功能障碍。黄连解毒汤（HLJDD）是一种著名的中药方剂，在临床实践中对治疗糖尿病和阿尔茨海默病有效，然而，HLJDD 对 DE 的治疗效果和作用机制尚不清楚。本研究旨在通过行为测试、脑组织学和生化分析来评估 HLJDD 对 DE 的有益作用。基于 UPLC-Q-Orbitrap HRMS/MS 和化学计量学分析，采集血浆样本进行代谢组学分析。结果表明，HLJDD 可有效改善 db/db 小鼠的学习和记忆能力。脑组织学和生化分析表明，HLJDD 可预防 db/db 小鼠的神经退行性变和氧化应激。同时，采用非靶向代谢组学策略，鉴定出 21 种具有显著差异的潜在生物标志物。其中，11 种代谢物经 HLJDD 干预后呈正常水平趋势。基于代谢途径分析，这些代谢物主要涉及甘油磷脂代谢、脂肪酸β-氧化、亚油酸代谢、葡萄糖代谢和谷胱甘肽代谢，这些代谢途径在 DE 模型小鼠中得到了调节。总的来说，这些结果表明 HLJDD 对 DE 具有有益作用，可能通过改善代谢紊乱来实现。
