Huangqi decoction attenuates renal interstitial fibrosis transforming growth factor-β1/mitogen-activated protein kinase signaling pathways in 5/6 nephrectomy mice

J Tradit Chin Med. 2022 Oct;42(5):723-731. doi: 10.19852/j.cnki.jtcm.2022.05.006.

Abstract

Objective: To investigate the effect of Huangqi decoction on renal interstitial fibrosis and its association with the transforming growth factor-β1 (TGF-β1) / mitogen-activated protein kinase (MAPK) signaling pathway.

Methods: 120 C57/BL mice were randomly divided into six groups: sham group, Enalapril (20 mg/kg) group, 5/6 nephrectomy model group, and 5/6 nephrectomy model plus Huangqicoction (0.12, 0.36 and 1.08 g/kg respectively) groups. Detecting 24hours urinary protein, blood pressure, serum creatinine, urea nitrogen content changes. Periodic Acid-Schiff stain (PAS) and Masson's trichrome staining was used to observe the renal tissue pathological changes. Protein expression of TGF-β1, Phosphorylated P38 mitogen activated protein kinases (P-P38), Phosphorylated c-jun N-terminal kinase (P-JNK), Phosphorylated extracellular regulated proteinhnase (P-ERK), Fibroblast-specific protein-1 (FSP-1), Alpha smooth muscle actin (α-SMA), Type III collagen (Collagen III), Connective tissue growth factor (CTGF), Bcl-2 Assaciated X protein (Bax) and B cell lymphoma 2 (Bcl-2) were measured with western blot and immunohistochemical.

Results: Both Huangqi decoction and Enalapril improved the kidney function, 24 h urinary protein and the fibrosis in 5/6 nephrectomy mice, Huangqi decoction downregulated the expressions of TGF-β1, FSP-1, α-SMA, Collagen III and CTGF in a dose-dependent manner, and it has a significant difference ( 0.01) compared with model group.Huangqi decoction downregulated the expressions of P-P38, P-JNK, P-ERK and Bcl-2 in a dose-dependent manner, while upregulated the expression of Bax.

Conclusions: The protective effect of Huangqi decoction for renal interstitial fibrosis in 5/6 nep-hrectomized mice the inhibition of Epithelial-Mesenchymal Transitions and downregulating the TGF-β1/ MAPK signaling pathway.

Keywords: Huangqi decoction; Signal transduction; mitogen-activated protein kinases; nephrectomy; renal interstitial fibrosis; transforming growth factor beta1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drugs, Chinese Herbal
  • Enalapril / metabolism
  • Enalapril / pharmacology
  • Fibrosis
  • Kidney
  • Kidney Diseases* / drug therapy
  • Kidney Diseases* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Nephrectomy
  • Signal Transduction
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Ureteral Obstruction* / complications
  • Ureteral Obstruction* / metabolism
  • Ureteral Obstruction* / pathology
  • bcl-2-Associated X Protein / metabolism

Substances

  • Drugs, Chinese Herbal
  • Transforming Growth Factor beta1
  • bcl-2-Associated X Protein
  • huangqi decoction
  • Enalapril
  • Mitogen-Activated Protein Kinases