Mitolactol

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^-1). 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.

Diabetes serves as a severe chronic disease that severely affects the normal life of human beings. Diabetes causes the complication of diabetic wound dysfunction, which is characterized by sustained inflammation, altered angiogenesis, delayed epithelialization and abnormal secretion of protease. Dang-Gui-Bu-Xue decoction (DBD) is a Chinese traditional medicine that comprises Radix Astragali and Radix Angelicae sinensis and is widely applied in treatment of multiple diseases owing to its functions against inflammation, lipid peroxidation and oxidative stress. Nevertheless, the impact of DBD on diabetic wound healing remains elusive. In this study, we aimed to explore the function of DBD in the regulation of wound healing. We observed that the gavage administration of DBD reduced the wound area, inflammatory infiltration, inflammatory factor levesl, and enhanced granulation tissue formation, wound extracellular matrix (ECM) production, and CD31 accumulation in the diabetic rat wound model, and the co-treatment of gavage administration and the external administration of gauze containing DBD further improved the wound healing effect, while the combination of Notch signaling inhibitor DAPT ((N- [N- (3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester)) could attenuate the improvement. Regarding to the mechanism, the expression levels of Notch1, Delta-like canonical Notch ligand 4 (Dll4), Jagged1, and Hairy Enhancer of Split-1 (Hes1) were increased by DBD, while the treatment of DAPT impaired the effect in the rats. Furthermore, we found that the high glucose (HG)-inhibited viability and tube formation were induced by DBD in human umbilical vein endothelial cells (HUVECs), in which DAPT could reverse this effect. Therefore, we concluded that DBD contributed to wound healing by the activation of Notch signaling. Our finding provides new insight into the potential role of DBD in promoting diabetic wound healing.