Improvement of Cisplatin-induced renal dysfunction by Schisandra chinensis stems via anti-inflammation and anti-apoptosis effects

J Ethnopharmacol. 2018 May 10:217:228-237. doi: 10.1016/j.jep.2018.01.033. Epub 2018 Feb 6.

Abstract

Ethnopharmacological relevance: Schisandra chinensis (Turcz.) Baill is a frequently used traditional Chinese medicine, and modern pharmacological research has proven that S. chinensis has antioxidant, anti-hepatotoxity, anti-inflammatory, and anti-nephrotoxic effects. Cisplatin is widely used as antineoplastic drug at present, but the clinical application is limited owing to its nephrotoxicity.

Aim of the study: To demonstrate the renoprotective activity of the extract of the stems of S. chinensis (SCE) in mice established by cisplatin-triggering acute kidney injury (AKI). The possible molecular mechanism of nephroprotection exhibited by SCE was evaluated for the first time.

Materials and methods: Mice in SCE groups were pre-treated with SCE for 10 consecutive days, and on 7th day 1 h after final administration, following intraperitoneal injection of cisplatin with 20 mg/kg was treated to cisplatin group and SCE groups. On the 10th day, renal function, histopathological change, and oxidative stress markers were investigated.

Results: Renal oxidative stress level characterized by elevated heme oxygenase 1 (HO-1), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) expression was obviously reduced by SCE pre-treatment. In addition, SCE was found to suppress inflammatory response through the reduction of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-κB) p65 activation. SCE treatment also inhibited activation of apoptotic pathways through down-regulating Bax, cleaved caspase-3, 8, 9 and up-regulating Bcl-2 expression levels.

Conclusion: These findings illustrated that SCE possessed powerful protective effect on AKI caused by cisplatin via amelioration of oxidative stress, inflammation and apoptosis.

Keywords: Apoptosis; Cisplatin-induced nephrotoxicity; Inflammation; Oxidative stress; SCE.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Aldehydes / metabolism
  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Cisplatin*
  • Cyclooxygenase 2 / metabolism
  • Cytochrome P-450 CYP2E1 / metabolism
  • Cytoprotection
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Heme Oxygenase-1 / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / physiopathology
  • Male
  • Membrane Proteins / metabolism
  • Mice, Inbred ICR
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress / drug effects
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Stems* / chemistry
  • Plants, Medicinal
  • Schisandra* / chemistry
  • Time Factors
  • Transcription Factor RelA / metabolism

Substances

  • Aldehydes
  • Anti-Inflammatory Agents
  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Membrane Proteins
  • Plant Extracts
  • Rela protein, mouse
  • Transcription Factor RelA
  • Cytochrome P-450 CYP2E1
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • 4-hydroxy-2-nonenal
  • Cisplatin