Mechanism of anti-diabetic, lipid inhibition and anti-oxidant activity of palmatine via proteomics

P. N. Okechukwu1, S. O. Ekeuku1, T. S. Sen1, S. N. Siyumbwa1, A. Simbun1, G. A. Akuwoah2, G. R. Froemming3. 1Biotechnology, UCSI University, Kuala Lumpur, MALAYSIA, 2Pharmaceutical Science, UCSI University, Kuala Lumpur, MALAYSIA, 3Institute of Pathology, Medical and Forensic Laboratories (I-PPerForM), University Technology Mara, Selangor, MALAYSIA.

Introduction: Our previous study has shown that Palmatine possess an anti-diabetic, lipid inhibition and anti-oxidant activity 1. Our current research was aimed at evaluating the mechanism of action of anti-diabetic, lipid inhibition and anti-oxidant effect of Palmatine via Proteomics Approach.

Method: In this study, Sprague Dawley rats were divided into: Normal, diabetic (negative) control, Palmatine (2mg/kg), Tolbutamide, (100mg/kg), 50 mg/kg of streptozotocin (STZ) was administered by intraperitoneal injection to induce diabetes; treatment was carried out for 12 weeks 2. Two dimensional gel electrophoresis (2-DE) and mass spectrometer (Proteomics technique) were used to analyze the differential protein expression in the pancreas. Mass spectrometry (MS/MS), multidimensional protein identification technology (MudPIT) and protein database were used to identify the proteins that were differentially expressed in the pancreas3. A potential biological process, function of the identified proteins and protein-protein interaction network (PPI) was constructed using STRING database with minimal confidence of 0.150.

Results: The pIs and MW of the identified proteins correspond to protein homologous; Anionic trypsin-2 (Prss2), chymotripsinogen (ctrb1), heat shock protein a5 or Glucose regulated protein (Hspa5/GRP), Selenium binding protein (Selenbp1), Trypsin V-A, pancreatic amylase 2A3 (Amy2A3), Protein disulfide isomerase A2/A3 (PDI A2/A3), pancreatic lipase (Pnlip), enoyl coA hydratase (Echs1), Transforming acid coiled-coil protein 2 (Tacc2), Voltage-dependent anion channel protein 2 (vdac2), bile salt-activated lipase (cel), ATP synthase B, Lactoyl glutathione lyase (Glo1), zinc finger protein (znf22), and serum albumin (Alb).

Conclusion: Treatment with Palmatine caused the expression of lipase inhibiting; ATP stimulating, heat shock, lipid inhibiting proteins, and antioxidant proteins. PPI network analysis showed that the identified proteins are involved in the cellular components.

Reference:

[1] Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015 Jan; 43:D447-52.

[2] Ekeuku S.O, Okechukwu P. N., Akowoah G.A., Sen, T.S.,Siyumbwa S.N. Froemming G.R.A.Plasma Glucose Lowering Activity of Palmatine and its Effect on Liver,Kidney and Antioxidant Enzymes Parameters in STZ Induced Diabetic Rat Model, Current Bioactive Compounds Journal, 11(4), 256-263.

[3] Ekeuku S.O, Okechukwu P. N., Akowoah G.A., Sen, T.S.,Siyumbwa S.N. Froemming G.R.A Antidiabetic Effect of Partially Purified Fraction E from the Stem Extract of Coscinium fenestratum, Global Journal of Pharmacology, 9 (4), 316-325.