The protective effect of Herba Cistanches on statin-induced myotoxicity in vitro

J Ethnopharmacol. 2016 Aug 22;190:68-73. doi: 10.1016/j.jep.2016.06.020. Epub 2016 Jun 7.


Ethnopharmacological relevance: Herba Cistanches (HC, Cistanche deserticola or Cistanche tubulosa) is a Chinese herb traditionally used for muscle problems. Previous studies demonstrated that HC extract could reduce muscle damage and improve ATP storage in post-exercised rats. However, its effect on statin-induced muscle toxicity has never been investigated.

Aim: The objective of this study was to determine if the aqueous extract of HC (HCE) could prevent simvastatin-induced toxicity in L6 rat skeletal muscle cells; and whether verbascoside is the major bioactive constituent which contributes to the effects.

Materials and methods: MTT was performed to determine the effects of HCE (0-2000µg/ml) or verbascoside (0-160µM) on simvastatin (10µM)-treated L6 cells. Annexin V-FITC/PI apoptosis assay and Caspase 3 assay were performed to determine the protective role of HCE on simvastatin-induced cell death, and to evaluate if HCE exerted its protective effect through the caspase pathway. ATP production was measured to investigate if HCE could prevent simvastatin-induced reduction in ATP production in vitro.

Results: Simvastatin significantly increased apoptotic cell death in L6 cells. HCE significantly exerted a dose-dependent reduction on simvastatin-induced apoptotic cells, possibly via caspase-3 pathway. Simvastatin reduced the ATP production in L6 cells, which was dose-dependently prevented by HCE. There was only a trend but not significant effect (except at high dose) of verbascoside on the protection of simvastatin-induced muscle toxicity.

Conclusions: In conclusion, we demonstrated for the first time that HCE could exert dose-dependent protective effect on simvastatin-induced toxicity in vitro, which was unlikely due to the presence of verbascoside. Our study suggested the potential use of HC under the situation of simvastatin-induced muscle toxicity.

Keywords: Caspase-3; Cholesterol; Herba Cistanches; Hyperlipidemia; Muscle toxicity; Statin; Verbascoside.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line
  • Chromatography, Liquid
  • Cistanche / chemistry*
  • Cytoprotection
  • Dose-Response Relationship, Drug
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / toxicity*
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscular Diseases / chemically induced
  • Muscular Diseases / metabolism
  • Muscular Diseases / pathology
  • Muscular Diseases / prevention & control*
  • Phenols / isolation & purification
  • Phenols / pharmacology*
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Protective Agents / isolation & purification
  • Protective Agents / pharmacology*
  • Rats
  • Simvastatin / toxicity*


  • Glucosides
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Phenols
  • Plant Extracts
  • Protective Agents
  • acteoside
  • Adenosine Triphosphate
  • Simvastatin
  • Casp3 protein, rat
  • Caspase 3