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Abstract
Background
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.
Abbreviations
AA, arachidonic acid; ACC, acetyl-coA carboxylase; AMPK, adenosine 5’ monophosphate activated protein kinase; CDP-DAG, cytidine diphosphate diacylglycerol; COX, cyclooxygenases; CYP450, cytochrome P450; CYP2C70, cytochrome P450 family 2 subfamily c polypeptide 70; CYP3A4, cytochrome P450 family 3 subfamily A member 4; DM, diabetes mellitus; FXR, farnesoid x activated receptor; G6Pase, glucose 6-phosphatase; GCA, glycocholic acid; GCDCA, glycochenodeoxycholic Acid; GLP-1, glucagon-like peptide-1; Glut4, glucose transporter protein 4; LACS, long-chain acyl-coenzyme A synthetase; LOX, lipoxygenases; LPA, lysophosphatidic acid; LT, leukotriene; LT B4, leukotriene B4; LT D4, leukotriene D4; PGB2, prostaglandin B2; PC, phosphatidylcholine; PCA, principal component analysis; PEPCK, phosphoenolpyruvate carboxykinase; PG, phosphatidylglycerol; PI, phosphatidylinositol; PGD2, prostaglandin D2; PGE2, prostaglandin E2; PGH2, prostaglandin H2; PGJ2, prostaglandins J2; PLS-DA, partial least squares discriminant analysis; PPAR, peroxisome proliferator-activated receptors; QC, quality control; S1P, sphingosine-1-phosphate; SD, Sprague-Dawley; SHP, small heterodimer partner; STZ, streptozotocin; TCM, traditional Chinese medicine; TCA, taurocholic acid, TX, thromboxanes, P. capitatum, Polygonum capitatum; UDCA, ursodeoxycholic acid, α -Gase, α -glucosidase; β-MCA, β-Muricholic acid.
Data Sharing Statement
The data generated in this study are available from the corresponding author upon request.
Ethics Approval and Consent to Participate
The animal study was reviewed and approved by the Animal Ethic Committee of Second Military Medical University.
Consent for Publication
Written informed consent was obtained from all researchers before writing this manuscript.
Acknowledgments
We want to express our gratitude to the current and former members of our laboratories and collaborators for their contributions to this article.
Author Contributions
Mingming Li, Xin Zhou, Doudou Huang are the first authors. Lianna Sun and Zhiying Dong are the corresponding author. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare that they have no competing interests in this work.