Bupleurum polysaccharides ameliorated renal injury in diabetic mice associated with suppression of HMGB1-TLR4 signaling

Chin J Nat Med. 2019 Sep;17(9):641-649. doi: 10.1016/S1875-5364(19)30078-0.

Abstract

Bupleurum polysaccharides (BPs) is isolated from Bupleurum smithii var. parvifolium, a key traditional Chinese medicine. The study was to investigate the effects of BPs on diabetic kidney injury. After two intraperitoneal injections of streptozotozin (STZ) 100 mg·kg-1, renal injury in diabetic mice was induced and BPs was orally administrated at dosages of 30 and 60 mg·kg-1·d-1. The STZ injected mice developed renal function damage, renal inflammation and fibrosis known as diabetic kidney disease (DKD). BPs significantly reduced serum creatinine level and urinary albumin excretion rate, with the attenuated swelling of kidneys. BPs treatment obviously alleviated the pathological damage of renal tissue. The progression of renal injury in BPs treated mice was inhibited with less expression of type IV collagen (Col IV), fibronectin (FN) and α-smooth muscle actin (α-SMA). The inhibition of inflammation in kidney was associated with the reduced level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). BPs administration suppressed the over-expression of toll like receptor 4 (TLR4) and high-mobility group box 1 (HMGB1) with lowered activity of nuclear factor kappa B (NF-κB) in renal tissue of diabetic mice. Oral administration of BPs effectively prevented the development ofrenal injury in diabetic mice. This study suggested that the protection provided by BPs might affect through the interruption of HMGB1-TLR4 pathway, leading to the inhibition of renal inflammation and fibrotic process.

Keywords: Bupleurum; High-mobility group box; Inflammation; Polysaccharides; Renal fibrosis; Renal injury; Toll-like receptor 4.

MeSH terms

  • Animals
  • Bupleurum / chemistry*
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use
  • HMGB1 Protein / metabolism*
  • Inflammation / metabolism
  • Inflammation / prevention & control
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mice, Inbred C57BL
  • Plant Roots / chemistry
  • Polysaccharides / administration & dosage
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use*
  • Signal Transduction / drug effects
  • Streptozocin / toxicity
  • Toll-Like Receptor 4 / metabolism*
  • Transcription Factor RelA / metabolism

Substances

  • Cytokines
  • Drugs, Chinese Herbal
  • HMGB1 Protein
  • HMGB1 protein, mouse
  • Polysaccharides
  • Rela protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Streptozocin