Metabolic Profiling of Carbonyl Compounds for Unveiling Protective Mechanisms of Pueraria lobata against Diabetic Nephropathy by UPLC-Q-Orbitrap HRMS/MS Analysis

Abstract

Carbonyl compounds play a critical role in the pathogenesis of diabetic nephropathy (DN). Pueraria lobata (PL), also known as “Kudzu”, is a widely consumed functional food or nutraceutical and has shown promise in the prevention of diabetes and complications such as DN. To explore the beneficial effects and the underlying mechanisms of PL against DN, a new strategy for in-depth metabolic profiling of carbonyl compounds in DN mice plasma by chemical derivatization combined with UPLC-Q-Orbitrap high-resolution mass spectrometry (HRMS)/MS analysis was developed for the first time. Pharmacological evaluation revealed that PL extracts containing a total of 73 identified compounds could ameliorate kidney injury and regulate abnormal glycolipid metabolism. In metabolomics analysis, 19 carbonyl compounds with significant differences were identified between DN mice and normal mice. Moreover, 12 metabolites had a tendency to return to normal levels after PL treatment. Overall, PL exerts beneficial effects on DN by regulating abnormal glycolipid metabolism and carbonyl stress, and endogenous carbonyl compounds might serve as potential biomarkers for DN.

Effects of natural dihydrochalcones in sweet tea (Lithocarpus polystachyus) on diabetes: a systematical review and meta-analysis of animal studies

“…AGEs are macromolecules generated by the Maillard reaction and can induce carbonyl stress. 48,49 Histopathological studies indicated that AGEs, formed and accumulated in vivo, play a pivotal role in the development of diabetes and its complications. 50 Whether DST can improve diabetes and its complications through AGEs still requires more research.…”

Pterostilbene could alleviate diabetic cognitive impairment by suppressing TLR4/NF‐кB pathway through microbiota‐gut‐brain axis

“…In this experiment, for DCI mice, the level of LPS, the protein expression of TLR4, MyD88, and p‐p65, and the levels of IL‐6 and IL‐1β in the colon and brain, as well as the protein expression of RAGEs in brain were higher than those of normal mice, indicating that there are intestinal inflammation and neuroinflammation in DCI mice. In addition, some abnormal biochemical indicators (Ach, MDA, SOD, and AGEs), the increase in GFAP and Iba‐1, and the loss of DN can also prove the existence of neuroinflammation in DCI mice (Chang et al, 2022; Kim & Song, 2020; La Barbera et al, 2021; Zhang, Guo, et al, 2021). Correlation analysis also showed a strong positive correlation between intestinal inflammation and neuroinflammation, consistent with previous studies (Welcome, 2019).…”

Hesperetin, a Promising Treatment Option for Diabetes and Related Complications: A Literature Review

“…As one of the crucial microvascular complications of DM, DN is also the primary cause of chronic kidney disease and end-stage renal disease (ESRD) . Pathological changes include glomerulosclerosis, mesangial cell hypertrophy, thickening of basement membranes, and renal fibrosis. − Currently, the treatments for DN focus on controlling glycaemic, controlling blood pressure with renin-angiotensin-aldosterone system inhibitors, and improving lifestyle. In addition, the discovery of some new targets also contributes to the research and development of DN new drugs, such as podocyte-endothelial communication .…”