Fu-Fang-Jin-Qian-Cao herbal granules protect against the calcium oxalate-induced renal EMT by inhibiting the TGF-β/smad pathway

Pharm Biol. 2020 Dec;58(1):1115-1122. doi: 10.1080/13880209.2020.1844241.

Abstract

Context: Nephrolithiasis is a major public health problem worldwide and Fu-Fang-Jin-Qian-Cao granules (FFJQC) is a traditional Chinese herbal formula that is used to treat nephrolithiasis. The main component of nephrolithiasis is calcium oxalate (CaOx) and the epithelial-mesenchymal transition (EMT) shown to play a crucial role in CaOx-induced kidney injury. However, the mechanism underlying the therapeutic effect of FFJQC on the CaOx-induced renal EMT is unknown.

Objective: This study explores the therapeutic benefits and mechanism of FFJQC in oxalate-induced kidney injury.

Materials and methods: 60 male C57BL/6 mice were used in this experiment and divided into 6 groups. A mouse kidney stone model was created by intraperitoneal injection of glyoxylate at a dose of 100 mg/kg for 6 days. The standardized FFJQC was used to treat mouse crystal kidney injury by gavage at 1.35 and 2.7 g/kg, respectively. Western blotting and immunostaining for E-cadherin, cytokeratin 18 (CK18), vimentin, smooth muscle α-actin (α-SMA) and transforming growth factor β (TGF-β)/Smad pathway were conducted on renal tissues.

Results: Following CaOx-induced kidney injury, the levels of E-cadherin and CK18 in kidney decreased, while vimentin and α-SMA levels increased. The FFJQC treatment increased the levels of E-cadherin and CK18 and decreased vimentin and α-SMA levels in varying degrees. What's more, the FFJQC reduced the expression of CaOx-induced fibrosis marker collagen II.

Conclusion: FFJQC alleviated the CaOx-induced renal EMT and fibrosis by regulating TGF-β/smad pathway. Therefore, the FFJQC is an important traditional Chinese medicine for the treatment of CaOx-induced renal injury and fibrosis.

Keywords: Oxalate crystals; renal fibrosis; traditional Chinese medicine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Calcium Oxalate / toxicity
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Kidney Calculi / prevention & control
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nephrolithiasis / prevention & control*
  • Signal Transduction / drug effects
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Cadherins
  • Drugs, Chinese Herbal
  • Smad Proteins
  • Transforming Growth Factor beta
  • Calcium Oxalate

Grants and funding

This study was supported by grants from Natural Science Foundation of China [81573759, 31771511 and 82074261], the Talents Training Program of Seventh People’s Hospital of Shanghai University of TCM [XX2018-07], the Summit Discipline of Clinical Traditional Chinese Medicine in Pudong New Area of Shanghai [PDZY-2018-0601], and the Innovation Fund for College Students of Second Military Medical University [FH2017182].