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Pharmacology & ToxicologybioRxiv

Anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory conditions induced by PTY-2 against STZ-induced stress in islets

S. Srivastava, H. Pandey, S. K. Singh, Y. B. Tripathi

Abstract

Background and AimEarlier assessment of Pueraria tuberosa tubers has shown anti-diabetic effects through incretin mimetic action and DPP-IV inhibition. The aim of this work was to further explore the protective role of aqueous extract of Pueraria tuberosa against streptozotocin (STZ)-induced pancreatic stress in rats.\n\nMethodsDiabetes was induced with STZ (65 mg/kg body weight) in Charles foster male rats. After 60 days of STZ administration, animals with blood glucose levels > 200 g/dL were considered as diabetic. All the rats were later divided into three groups: Group-1 (STZ untreated normal rats), Group-2 (Diabetic control), and Group-3 (PTY-2 [50 mg/100 g bw treatment for next 10 days to diabetic rats). The rats were then sacrificed at the 10th day of treatment accordingly.\n\nResultsSTZ treatment led to an increase in expression of MMP-9, Tnf , HIF-1, VEGF, IL-6, PKC {varepsilon}, NF-kB, and Caspase-3. Reverse transcriptase Polymerase Chain Reaction (PCR), IHC and western blot analysis showed an increase in the expressions of superoxide dismutase (SOD) and Nephrin, and a decrease in the expressions of NF-kB, PKC {varepsilon}, TNF- MMP-9, HIF-1, VEGF, Caspase 3 and IL-6 after 10 days of PTY-2 treatment.\n\nConclusionThe results show that PTY-2 favorably changed the expression of NF-kB, PKC {varepsilon}, TNF , MMP 9, HIF-1, VEGF, IL-6, Caspase3, Nephrin and SOD in cases of STZ-induced pancreatic stress. Further evaluation of PTY-2 might be helpful in establishing its role in the management of diabetes mellitus.\n\nHighlightsO_LIPTY 2 act as a protective herbal drug against STZ induced islet stress.\nC_LIO_LIPTY 2 upregulates protective and downregulates harmful markers.\nC_LIO_LIThis study composed of four pathway through which PTY 2 acts on pancreas.\nC_LI\n\nGRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC=\"FIGDIR/small/670364v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (69K):\norg.highwire.dtl.DTLVardef@14b1f18org.highwire.dtl.DTLVardef@e6a1f2org.highwire.dtl.DTLVardef@19225b0org.highwire.dtl.DTLVardef@1e87bf5_HPS_FORMAT_FIGEXP M_FIG Mechanism of action of PTY 2 against STZ induced islet stress.\n\nC_FIG

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