Drug Design, Development and Therapy (Jun 2024)
Unveiling the Pharmacological Mechanisms of Davidiin’s Anti-Diabetic Efficacy in Streptozotocin-Treated Rats: A Comprehensive Analysis of Serum Metabolome
Abstract
Mingming Li,1,2,* Xin Zhou,1,* Doudou Huang,1,* Yingkui Zhao,2 Jiani Chen,2 Zhiying Dong,1 Wansheng Chen,1,2 Feng Zhang,2 Lianna Sun1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lianna Sun; Wansheng Chen, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, People’s Republic of China, Tel +86-13818946096 ; +86-15901818646, Email [email protected]; [email protected]: Polygonum capitatum Buch.-Ham. ex D. Don (P. capitatum), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties.Materials and Methods: Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS.Results: Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins.Conclusion: Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin’s action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.Keywords: diabetes mellitus, streptozotocin, metformin, davidiin, metabolomics
