Scutellarin protects against the liver injury induced by diosbulbin B in mice and its mechanism

J Ethnopharmacol. 2015 Apr 22;164:301-8. doi: 10.1016/j.jep.2015.02.031. Epub 2015 Feb 19.

Abstract

Ethnopharmacological relevance: Diosbulbin B (DB) is the main hepatotoxic compound distributed in Dioscorea bulbifera L., which is widely used for the treatment of cancer and thyroid disorders in Asia. Scutellarin (SC) is the main compound in medicinal herb Scutellaria barbata D. Don, which is usually combined with Dioscorea bulbifera used for cancer therapy in clinic.

Aim of the study: This study aims to investigate the protection of SC against the liver injury induced by DB and its engaged mechanism. In addition, the anti-tumor effect of DB and SC is further observed in vivo.

Materials and methods: The protection of SC against DB-induced liver injury was evaluated by detecting serum alanine/aspartate aminotransferases (ALT/AST) and alkaline phosphatase (ALP) activities, and further liver histological observation. The inflammatory response was assessed by detecting liver myeloperoxidase (MPO) activity, and serum levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interferon-γ (IFN-γ). Western-blot analysis was used to detect the protein expression. The oxidative liver injury was evaluated by detecting liver malondialdehyde (MDA) and glutathione (GSH) contents, and glutathione peroxidase (GPx) enzymatic activity. In vivo anti-tumor activity was analyzed in S180 tumor-bearing mice.

Results: SC significantly decreased the increased serum ALT/AST, and ALP activities induced by DB. Liver histological observation evidenced the protection of SC against DB-induced liver injury. SC obviously reduced the increased liver MPO activity and the number of MPO-positive staining cells induced by DB. SC also reversed the decreased expression of inhibitor of κB (IκB) and the translocation of nuclear factor κB (NF-κB) p65 from cytoplasm to nucleus induced by DB. In addition, SC significantly abrogated the increased serum levels of TNF-α, IL-6, and IFN-γ induced by DB. SC decreased the increased liver MDA content induced by DB significantly, and it also increased liver GSH level. The decreased GPx protein expression and its enzymatic activity induced by DB were both obviously reversed after SC treatment. The results in S180 tumor-bearing mice showed that SC combined with DB significantly inhibited tumor growth in vivo.

Conclusions: Our results demonstrate that SC prevents DB-induced liver injury by attenuating NF-κB-mediated hepatic inflammation and ameliorating liver oxidative stress injury. Meanwhile, DB plus SC has significant anti-tumor activity in vivo. This study indicates the potential combination of DB with SC for the treatment of cancer in clinic.

Keywords: Anti-tumor; Diosbulbin B; Hepatotoxicity; Inflammation; Oxidative stress injury; Scutellarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apigenin / pharmacology
  • Apigenin / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Cell Line, Tumor
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Cytokines / blood
  • Glucuronates / pharmacology
  • Glucuronates / therapeutic use*
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Heterocyclic Compounds, 4 or More Rings / adverse effects*
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice, Inbred ICR
  • NF-kappa B
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Cytokines
  • Glucuronates
  • Heterocyclic Compounds, 4 or More Rings
  • NF-kappa B
  • Protective Agents
  • scutellarin
  • diosbulbin B
  • Apigenin
  • Glutathione Peroxidase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Glutathione