Camptosorus sibiricus rupr aqueous extract prevents lung tumorigenesis via dual effects against ROS and DNA damage

J Ethnopharmacol. 2018 Jun 28;220:44-56. doi: 10.1016/j.jep.2017.12.021. Epub 2017 Dec 16.

Abstract

Ethnopharmacological relevance: Camptosorus sibiricus Rupr (CSR) is a widely used herbal medicine with antivasculitis, antitrauma, and antitumor effects. However, the effect of CSR aqueous extract on B[a]P-initiated tumorigenesis and the underlying mechanism remain unclear. Moreover, the compounds in CSR aqueous extract need to be identified and structurally characterized.

Aim of the study: We aim to investigate the chemopreventive effect of CSR and the underlying molecular mechanism.

Materials and methods: A B[a]P-stimulated normal cell model (BEAS.2B) and lung adenocarcinoma animal model were established on A/J mice. In B[a]P-treated BEAS.2B cells, the protective effects of CSR aqueous extract on B[a]P-induced DNA damage and ROS production were evaluated through flow cytometry, Western blot, real-time quantitative PCR, single-cell gel electrophoresis, and immunofluorescence. Moreover, a model of B[a]P-initiated lung adenocarcinoma was established on A/J mice to determine the chemopreventive effect of CSR in vivo. The underlying mechanism was analyzed via immunohistochemistry and microscopy. Furthermore, the new compounds in CSR aqueous extract were isolated and structurally characterized using IR, HR-ESI-MS, and 1D and 2D NMR spectroscopy.

Results: CSR effectively suppressed ROS production by re-activating Nrf2-mediated reductases HO-1 and NQO-1. Simultaneously, CSR attenuated the DNA damage of BEAS.2B cells in the presence of B[a]P. Moreover, CSR at 1.5 and 3 g/kg significantly suppressed tumorigenesis with tumor inhibition ratios of 36.65% and 65.80%, respectively. The tumor volume, tumor size, and multiplicity of B[a]P-induced lung adenocarcinoma were effectively decreased by CSR in vivo. After extracting and identifying the compounds in CSR aqueous extract, three new triterpene saponins were isolated and characterized structurally.

Conclusions: CSR aqueous extract prevents lung tumorigenesis by exerting dual effects against ROS and DNA damage, suggesting that CSR is a novel and effective agent for B[a]P-induced carcinogenesis. Moreover, by isolating and structurally characterizing three new triterpene saponins, our study further standardized the quality of CSR aqueous extract, which could widen CSR clinical applications.

Keywords: Benzo(a)pyrene; Camptosorus sibiricus Rupr; DNA damage; Lung cancer; ROS.

MeSH terms

  • Adenocarcinoma / prevention & control*
  • Adenocarcinoma of Lung
  • Animals
  • Anticarcinogenic Agents / isolation & purification
  • Anticarcinogenic Agents / pharmacology*
  • Benzo(a)pyrene / toxicity
  • Blotting, Western
  • DNA Damage / drug effects
  • Ferns / chemistry*
  • Flow Cytometry
  • Humans
  • Lung Neoplasms / prevention & control*
  • Mice
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Saponins / isolation & purification
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification

Substances

  • Anticarcinogenic Agents
  • Plant Extracts
  • Reactive Oxygen Species
  • Saponins
  • Triterpenes
  • Benzo(a)pyrene