School of Pharmacy, Nanjing University of Chinese Medicine, Jiangsu Engineering Research Center for Development and Application of External Drugs in Traditional Chinese Medicine, Jiangsu Province Engineering Research Center of Classical Prescription, Nanjing 210023, China.
School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guizhou 550000, China.
Phytomedicine. 2024 Dec;135:156104. doi: 10.1016/j.phymed.2024.156104. Epub 2024 Sep 29.
Dang-Gui-Bu-Xue decoction (DBD) is a traditional Chinese medicine prescription clinically employed for diabetic nephropathy (DN). However, the components and pharmacological mechanisms of DBD against DN remain incompletely understood.
To clarify the beneficial effect of DBD on DN and to explore its nephroprotective effect's probable mechanism and the main components.
A diabetic mice model was established by feeding a high-fat diet (HFD) and intraperitoneal injections of streptozotocin (STZ, 40 mg‧kg). Subsequently, the mice were maintained on a HFD and administered with DBD. The benefits of DBD against DN were comprehensively assessed by monitoring energy and water intake, blood glucose and lipids, renal functions and pathological status. The UPLC-MS/MS was measured to detect chemical constituents in DBD and absorbed components in DBD-treated plasma under physiological and pathological states. Network pharmacology was employed to forecast the probable pathways of DBD intervention in DN, with subsequent validation of these predictions through testing biochemical parameters, anti-glycation and ELISA assays, immunofluorescence, immunohistochemistry, and western blotting. Then, a chemical derivatization method paired with UPLC-MS/MS analysis was performed to detect the carbonyl compounds in renal tissue. Finally, the main components of DBD against DN were screened by anti-glycation and MTT assays.
DBD regulated energy and water intakes, glucose and lipid metabolism disorders, renal dysfunction, glomerular filtration rate, renal interstitial glycogen accumulation and fibrosis in HFD/STZ-induced DN mice. A total of 129 distinct chemical constituents in DBD were characterized, of which 28 were detected in the DBD-treated plasma under a pathological state. The network pharmacological results suggested AGEs/RAGE and its downstream pathway may be a potential pathway for DBD intervention in DN. Further experiments confirmed that DBD reduced renal oxidative stress by modulating the AGEs/RAGE pathway. Moreover, 21 differential carbonyl compounds were detected between normal and DN mice, and DBD significantly modulated 16. Ultimately, seven components were screened out in DBD, which may be the main components of DBD regulating carbonyl compounds metabolic profile and AGEs/RAGE pathway.
Our findings suggested for the first time that DBD could regulate the carbonyl compounds metabolic profile and AGEs/RAGE signaling pathway to ameliorate DN.
当归补血汤（DBD）是一种临床上用于治疗糖尿病肾病（DN）的中药方剂。然而，DBD 治疗 DN 的成分和药理机制仍不完全清楚。
阐明 DBD 对 DN 的有益作用，并探讨其肾保护作用的可能机制和主要成分。
通过给予高脂肪饮食（HFD）和腹腔注射链脲佐菌素（STZ，40mg·kg）建立糖尿病小鼠模型。随后，将小鼠维持在 HFD 并给予 DBD。通过监测能量和水摄入、血糖和血脂、肾功能和病理状态，综合评估 DBD 对 DN 的益处。采用 UPLC-MS/MS 检测 DBD 中的化学成分和 DBD 处理后的血浆中吸收的成分在生理和病理状态下。通过测试生化参数、抗糖基化和 ELISA 测定、免疫荧光、免疫组织化学和 Western blot 验证网络药理学预测的 DBD 干预 DN 的可能途径。然后，采用化学衍生化方法结合 UPLC-MS/MS 分析检测肾组织中的羰基化合物。最后，通过抗糖基化和 MTT 测定筛选 DBD 治疗 DN 的主要成分。
DBD 调节了 HFD/STZ 诱导的 DN 小鼠的能量和水摄入、糖脂代谢紊乱、肾功能障碍、肾小球滤过率、肾间质糖原积累和纤维化。在 DBD 中鉴定出 129 种不同的化学成分，其中 28 种在病理状态下的 DBD 处理血浆中检测到。网络药理学结果表明 AGEs/RAGE 及其下游途径可能是 DBD 干预 DN 的潜在途径。进一步的实验证实，DBD 通过调节 AGEs/RAGE 途径减轻了肾脏氧化应激。此外，在正常和 DN 小鼠之间检测到 21 种差异羰基化合物，DBD 显著调节了其中的 16 种。最终，从 DBD 中筛选出 7 种成分，它们可能是 DBD 调节羰基化合物代谢谱和 AGEs/RAGE 途径的主要成分。
我们的研究结果首次表明，DBD 可以调节羰基化合物代谢谱和 AGEs/RAGE 信号通路，改善 DN。
