Abstract
Portulaca oleracea L., known as the “vegetable for long life,” is an annual succulent herb that is widely distributed worldwide. Many clinical and experimental studies have demonstrated that purslane seed (MCXZ) can be used as an adjunctive and alternative therapy for the treatment of diabetes mellitus (DM). However, the underlying active constituents and pharmacological mechanisms through which MCXZ exerts effects in DM remain unclear. In the present study, we confirmed that MCXZ treatment resulted in hypoglycemic activity, lowering the fasting blood glucose and glycated hemoglobin levels in streptozotocin-induced diabetic mice. Then, ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry was used to systematically analyze the chemical profile of MCXZ, resulting in the identification of 84 constituents, including 31 organic acids and nine flavonoids. Finally, the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine was employed to analyze the key active components of MCXZ and the molecular mechanisms through which these components acted in DM. Ten key active compounds were identified based on the topological importance of their corresponding putative targets within the known DM-associated therapeutic target network of known MCXZ putative targets. Functionally, these candidate targets play critical anti-hyperlipidemia, anti-hyperglycemia, immunity regulation, and inflammatory roles involving DM-related pathways, such as the vascular endothelial growth factor (VEGF) signaling pathway and Fc gamma R-mediated phagocytosis, which indicated that MCXZ exhibited anti-diabetic activity through multi-faced actions.
Highlights
Diabetes mellitus (DM) represents a major public health issue, causing serious economic burdens for both developed and developing countries (Papatheodorou et al, 2018)
We found that MCXZ alone was able to directly reduce the levels of fasting blood glucose (FBG) and HbA1c in STZinduced DM model mice, and the hypoglycemic effect of the lowdose MCXZ group was found to be better than the middle- and high-dose groups, which may be attributed to lower drug concentrations being more beneficial to digestion and absorption by the gastrointestinal tract
We found that DM upregulated the expression levels of Akt1, vascular endothelial growth factor (VEGF), erb-b2 receptor tyrosine kinase 2 (ErbB2), and androgen receptor (AR) in pancreatic tissue, which is consistent with other literature (Li et al, 2019; Momeny et al, 2019; Srivastava et al, 2019; Zhang et al, 2019)
Summary
Diabetes mellitus (DM) represents a major public health issue, causing serious economic burdens for both developed and developing countries (Papatheodorou et al, 2018). Persistent hyperglycemia and long-term metabolic disorders may lead to the development of nephropathy, retinopathy, neuropathy, and cardiovascular disease (Zhang H. et al, 2018). The drugs used to treat DM include biguanide, sulfonylureas, α-glycosidase inhibitors, benzoin acid, and derivative secretagogues, most of which aim to control blood glucose levels and must be used longterm. Gradual increases in the required doses of these drugs can lead to liver and kidney dysfunction, which can be associated with various complications, in addition to those resulting from the disease process (Moukette et al, 2017). The development of safer, more effective drugs, especially those derived from natural products, which can provide improved management for blood glucose and diabetes-associated complications, has long been the focus of DM studies
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