High doses of baicalin induces kidney injury and fibrosis through regulating TGF-β/Smad signaling pathway

Toxicol Appl Pharmacol. 2017 Oct 15:333:1-9. doi: 10.1016/j.taap.2017.08.003. Epub 2017 Aug 10.

Abstract

Baicalin is a major flavonoid compound purified from Scutellariae radix, which has been described as an herb in the Chinese Pharmacopoeia. Previous studies have suggested baicalin possessed extensive anti-inflammatory, anti-cancer, anti-viral properties. However, up to known, there have been no reports of safety and toxicity in the rats following oral administration of baicalin. In this present study, we showed the first evidence that treatment of baicalin (400, 800 and 1600mg/kg/day) induced significantly kidney injury and fibrosis. The collagen synthesis and fibrosis-related protein expression were increased in the kidney of Sprague-Dawley (SD) rats after treatment with high doses of baicalin. We further investigated the potential molecular mechanism of baicalin-mediated renal fibrosis and revealed that baicalin activated the transforming growth factor-β (TGF-β)/Smad signaling pathway in a dose-dependent manner. Moreover, we also observed that baicalin induced Smad3 interaction with transcriptional coactivator p300 accompanying with increment of Smad3 acetylation. Our results may contribute to better understanding of the future pharmacological and toxicological studies of Scutellaria baicalensis Georgi and its active compounds on the human disease.

Keywords: Baicalin; Fibrosis; Kidney injury; TGF-β/Smad signaling pathway; Toxicity.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Antineoplastic Agents / toxicity
  • Antiviral Agents / toxicity
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Fibrosis
  • Flavonoids / toxicity*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Rats, Sprague-Dawley
  • Scutellaria baicalensis
  • Signal Transduction / drug effects
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Acta2 protein, rat
  • Actins
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Antiviral Agents
  • CCN2 protein, rat
  • Fibronectins
  • Flavonoids
  • Smad3 Protein
  • Smad3 protein, rat
  • Transforming Growth Factor beta1
  • Connective Tissue Growth Factor
  • baicalin