Paeoniflorin attenuates incipient diabetic nephropathy in streptozotocin-induced mice by the suppression of the Toll-like receptor-2 signaling pathway

Drug Des Devel Ther. 2017 Nov 9:11:3221-3233. doi: 10.2147/DDDT.S149504. eCollection 2017.

Abstract

Toll-like receptors (TLRs) may be involved in diabetic nephropathy (DN). Paeoniflorin (PF) is an effective Chinese traditional medicine with anti-inflammatory and immunoregulatory effects that may inhibit the TLR2 signaling pathway. In this study, we investigated the effects of PF on the kidneys of mice with streptozotocin-induced type 1 diabetes mellitus using TLR2 knockout mice (TLR2-/-) and wild-type littermates (C57BL/6J-WT). After 12 weeks of intraperitoneal injection of PF at doses of 25, 50, and 100 mg/kg once a day, diabetic mice had significantly reduced albuminuria and attenuated renal histopathology. These changes were associated with substantially alleviated macrophage infiltration and decreased expression of TLR2 signaling pathway biomarkers. These data support a role of TLR2 in promoting inflammation and indicate that the effect of PF is associated with the inhibition of the TLR2 pathway in the kidneys of diabetic mice. PF thus shows therapeutic potential for the prevention and treatment of DN.

Keywords: DN; TLR2; Toll-like receptors 2; diabetic nephropathy; inflammation; macrophages; paeoniflorin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / pathology
  • Dose-Response Relationship, Drug
  • Glucosides / chemistry
  • Glucosides / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Conformation
  • Monoterpenes / chemistry
  • Monoterpenes / pharmacology*
  • Signal Transduction / drug effects*
  • Streptozocin
  • Structure-Activity Relationship
  • Toll-Like Receptor 2 / antagonists & inhibitors*
  • Toll-Like Receptor 2 / deficiency
  • Toll-Like Receptor 2 / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Glucosides
  • Monoterpenes
  • Toll-Like Receptor 2
  • peoniflorin
  • Streptozocin