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


OBJECTIVE
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.


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.
Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Elaine
E
Wat
Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Chun Fai
CF
Ng
Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Chi Man
CM
Koon
Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Eric Chun Wai
EC
Wong
Division of Clinical Pharmacology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Brian
B
Tomlinson
Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. Electronic address: claralau@cuhk.edu.hk.
Clara Bik San
CB
Lau
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002853:Chromatography, Liquid; D031671:Cistanche / Q000737:chemistry*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D019821:Simvastatin / Q000633:toxicity*; D059808:Polyphenols
D000255:Adenosine Triphosphate; D053148:Caspase 3; D005960:Glucosides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010636:Phenols; D010936:Plant Extracts; D020011:Protective Agents; D019821:Simvastatin; C058956:acteoside; D059808:Polyphenols; C505410:Casp3 protein, rat
Caspase-3; Cholesterol; Herba Cistanches; Hyperlipidemia; Muscle toxicity; Statin; Verbascoside