Quercetin/Zinc complex and stem cells: A new drug therapy to ameliorate glycometabolic control and pulmonary dysfunction in diabetes mellitus: Structural characterization and genetic studies

PLoS One. 2021 Mar 4;16(3):e0246265. doi: 10.1371/journal.pone.0246265. eCollection 2021.

Abstract

Medicinal uses and applications of metals and their complexes are of increasing clinical and commercial importance. The ligation behavior of quercetin (Q), which is a flavonoid, and its Zn (II) (Q/Zn) complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FTIR) spectra, electronic spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetric analysis, and transmission electron microscopy (TEM). FTIR spectral data revealed that Q acts as a bidentate ligand (chelating ligand) through carbonyl C(4) = O oxygen and phenolic C(3)-OH oxygen in conjugation with Zn. Electronic, FTIR, and 1H-NMR spectral data revealed that the Q/Zn complex has a distorted octahedral geometry, with the following chemical formula: [Zn(Q)(NO3)(H2O)2].5H2O. Diabetes was induced by streptozotocin (STZ) injection. A total of 70 male albino rats were divided into seven groups: control, diabetic untreated group and diabetic groups treated with either MSCs and/or Q and/or Q/Zn or their combination. Serum insulin, glucose, C-peptide, glycosylated hemoglobin, lipid profile, and enzymatic and non-enzymatic antioxidant levels were determined. Pancreatic and lung histology and TEM for pancreatic tissues in addition to gene expression of both SOD and CAT in pulmonary tissues were evaluated. MSCs in combination with Q/Zn therapy exhibited potent protective effects against STZ induced hyperglycemia and suppressed oxidative stress, genotoxicity, glycometabolic disturbances, and structural alterations. Engrafted MSCs were found inside pancreatic tissue at the end of the experiment. In conclusion, Q/Zn with MSC therapy produced a synergistic effect against oxidative stress and genotoxicity and can be considered potential ameliorative therapy against diabetes with pulmonary dysfunction, which may benefit against COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • C-Peptide / metabolism
  • Cells, Cultured
  • Coordination Complexes / chemistry
  • Coordination Complexes / therapeutic use
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism
  • Hyperglycemia / blood
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Hyperglycemia / therapy
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Oxidative Stress / drug effects
  • Quercetin / analogs & derivatives
  • Quercetin / therapeutic use*
  • Rats
  • Zinc / chemistry
  • Zinc / therapeutic use*

Substances

  • Blood Glucose
  • C-Peptide
  • Coordination Complexes
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Quercetin
  • Zinc

Grants and funding

This work was supported by the grant from Deanship of Scientific Research, Taif University, Saudi Arabia under Research Group project Grants No. 6144-440-1.