Can Herba Cistanches protect against statin-induced muscle toxicity?

Statins, the cholesterol lowering drugs, are well known to cause myotoxicity in some patients [1]. Herba Cistanches (HC, Cistanche deserticola) is a Chinese herb traditionally used for muscle problems. Recent studies showed that HC extract could reduce muscle damage and improve ATP storage in post-exercised mice [2], though its effect (including its chemical marker verbascoside) on statin-induced muscle toxicity has never been investigated. Hence, we hypothesized that HC could prevent muscle toxicity induced by statins. The assessment was made on the basis of the in vitro and in vivo abilities of HC water extract (HCE) to reduce simvastatin-induced muscle toxicity.

Our in vitro data demonstrated that HCE (0 – 2 mg/ml) could exert dose-dependent protective effect on simvastatin (10µM)-induced apoptotic and necrotic cells, possibly via caspase-3 pathway. Simvastatin reduced the ATP production in L6 cells, which was dose-dependently prevented by HCE. However, there was no significant effect of verbascoside (0 – 160µM) on the protection of simvastatin-induced muscle toxicity. In our in vivo simvastatin-induced muscle toxicity rat model, results showed that simvastatin (640 mg/kg) significantly reduced quadriceps and gastrocnemius muscle weight. Both HCE (1.1 and 2.2 g/kg) and verbascoside (1.87 and 3.74 mg/kg) dose-dependently improved the muscle weights of both muscles. HCE, but not verbascoside, also significantly reduced simvastatin-induced increase in plasma creatine kinase levels. Simvastatin caused a significant reduction on muscle mitochondrial permeability potential and reactive oxygen species levels, which could be reversed by HCE.

In conclusion, we have for the first time demonstrated that HCE could significantly improve the simvastatin-induced muscle toxicity in vitro and in vivo, while verbascoside might be partly responsible for the effect. These data indicate the potential adjuvant use of HCE in patients who suffer from simvastatin-induced myotoxicity.

Acknowledgements: This project was financially supported by Food and Health Bureau HKSAR, Health and Medical Research Fund no. 11120831.

Keywords: Herba Cistanches, simvastatin, verbascoside, muscle toxicity, cholesterol.

References:

[1] Sathasivam S, Lecky B. Statin induced myopathy. BMJ 2008; 337: 1159 – 1162

[2] Cai RL, Yang MH, Shi Y, Chen J, Li YC, Qi Y. Antifatigue activity of phenylethanoid-rich extract from Cistanche deserticola. Phytother Res 2010; 24: 313 – 315