Schisandrin B Improves the Renal Function of IgA Nephropathy Rats Through Inhibition of the NF-κB Signalling Pathway

Inflammation. 2019 Jun;42(3):884-894. doi: 10.1007/s10753-018-0943-z.

Abstract

Schisandrin B (SchB) is an active compound extracted from the Chinese herb Schisandra chinensis and shows excellent anti-inflammatory activity. This study was performed to examine the effects of SchB in a rat model of IgA nephropathy (IgAN). IgAN was established in Sprague-Dawley rats by immunization with lipopolysaccharide (LPS), bovine serum albumin, and carbon tetrachloride. Renal function was evaluated by determining the levels of urinary red blood cells, proteinuria, blood urea nitrogen (BUN), and creatinine (Cr). Renal tissue and protein samples were collected for further analysis. Pre-treatment and treatment with SchB significantly ameliorated renal function of IgAN rats, which was evidenced by decreased levels of proteinuria, hematuria, BUN, and Cr. IgAN rats exhibited increased serum IgA, renal IgA deposition, mesangial cell proliferation, and inflammatory cell infiltration, which were significantly attenuated by intervention with SchB. Moreover, SchB inhibited infiltration of CD3+ and CD11b+ cells, decreased levels of tumour necrosis factor-alpha, interleukin-1β, and monocyte chemoattractant protein-1 in the kidney, and decreased the numbers of CD3+CD69+ cells in the spleen. Of note, SchB therapy significantly increased cytoplasmic p65 and IκB expression and decreased nuclear p65 levels both in the damaged renal tissue and LPS-stimulated HK-2 cells, indicating a direct inhibitory effect on the NF-κB pathway in IgAN rats. Taken together, our data provide insight into a new application of SchB for the treatment of IgAN and represent a novel mechanism behind these effects.

Keywords: IgA nephropathy; NF-κB; TNF-alpha; renal function; schisandrin B.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cyclooctanes / pharmacology
  • Cyclooctanes / therapeutic use
  • Disease Models, Animal
  • Glomerulonephritis, IGA / drug therapy*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / physiopathology
  • Kidney Function Tests
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • NF-kappa B / antagonists & inhibitors*
  • Polycyclic Compounds / pharmacology*
  • Polycyclic Compounds / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Spleen / pathology

Substances

  • Anti-Inflammatory Agents
  • Cyclooctanes
  • Lignans
  • NF-kappa B
  • Polycyclic Compounds
  • schizandrin B