Statins are the most widely prescribed cholesterol-lowering drugs to reduce the risk of cardiovascular diseases. Statin-induced myopathy is the major side effect of this class of drugs. Here, we studied whether standardized leaf extracts of ginkgo biloba (EGb761) would improve simvastatin (SIM)-induced muscle changes. Sixty Wistar rats were allotted into six groups: control group, vehicle group receiving 0.5% carboxymethyl cellulose (CMC) for 30 days, SIM group receiving 80 mg/kg/day SIM in 0.5% CMC orally for 30 days, SIM withdrawal group treated with SIM for 16 days and sacrificed 14 days later, and EGb761-100 and EGb761-200 groups posttreated with either 100 or 200 mg/kg/day EGb761 orally. Muscle performance on the rotarod, serum creatine kinase (CK), coenzyme Q10 (CoQ10), serum and muscle nitrite, muscle malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities were estimated. Additionally, muscle samples were processed for histopathological evaluation. We found that SIM decreased muscle performance on the rotarod, serum CoQ10, as well as muscle SOD and CAT activities while it increased serum CK, serum and muscle nitrite, as well as muscle MDA levels. SIM also induced sarcoplasmic vacuolation, splitting of myofibers, disorganization of sarcomeres, and disintegration of myofilaments. In contrast, posttreatment with EGb761 increased muscle performance, serum CoQ10, as well as muscle SOD and CAT activities while it reduced serum CK as well as serum and muscle nitrite levels in a dose-dependent manner. Additionally, EGb761 reversed SIM-induced histopathological changes with better results obtained by its higher dose. Interestingly, SIM withdrawal increased muscle performance on the rotarod, reduce serum CK and CoQ10, and reduced serum and muscle nitrite while it reversed SIM-induced histopathological changes. However, SIM withdrawal was not effective enough to restore their normal values. Additionally, SIM withdrawal did not improve SIM-induce muscle MDA, SOD, or CAT activities during the period studied. Our results suggest that EGb761 posttreatment reversed SIM-induces muscle changes possibly through its antioxidant effects, elevation of CoQ10 levels, and antagonizing mitochondrial damage.

中文翻译：

---

银杏标准化提取物 (EGb761) 减轻辛伐他汀诱导的大鼠肌病：作用机制的洞察

他汀类药物是使用最广泛的降胆固醇药物，可降低心血管疾病的风险。他汀类药物引起的肌病是此类药物的主要副作用。在这里，我们研究了标准化的银杏叶提取物 (EGb761) 是否会改善辛伐他汀 (SIM) 诱导的肌肉变化。60只Wistar大鼠分为六组：对照组，载体组接受0.5％羧甲基纤维素（CMC）治疗30天，SIM组接受口服80mg / kg /天SIM的0.5％CMC治疗30天，SIM戒断组SIM 16 天，14 天后处死，EGb761-100 和EGb761-200 组口服100 或200 mg/kg/天EGb761 进行后处理。旋转棒上的肌肉性能、血清肌酸激酶 (CK)、辅酶 Q10 (CoQ10)、血清和肌肉亚硝酸盐、肌肉丙二醛 (MDA)、估计超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 活性。此外，还对肌肉样本进行了组织病理学评估。我们发现 SIM 降低了旋转棒的肌肉性能、血清 CoQ10 以及肌肉 SOD 和 CAT 活性，同时增加了血清 CK、血清和肌肉亚硝酸盐以及肌肉 MDA 水平。SIM 还诱导肌浆空泡化、肌纤维分裂、肌节解体和肌丝解体。相比之下，EGb761 后处理可增加肌肉性能、血清 CoQ10 以及肌肉 SOD 和 CAT 活性，同时以剂量依赖性方式降低血清 CK 以及血清和肌肉亚硝酸盐水平。此外，EGb761 逆转了 SIM 诱导的组织病理学变化，其较高剂量获得了更好的结果。有趣的是，SIM 停用提高了旋转棒上的肌肉性能，降低了血清 CK 和 CoQ10，并降低了血清和肌肉亚硝酸盐，同时逆转了 SIM 诱导的组织病理学变化。但是，SIM 卡取款并不足以恢复其正常值。此外，在研究期间，SIM 停用并未改善 SIM 诱导的肌肉 MDA、SOD 或 CAT 活动。我们的结果表明，EGb761 后处理逆转了 SIM 诱导的肌肉变化，可能是通过其抗氧化作用、CoQ10 水平升高和拮抗线粒体损伤。在研究期间，SIM 停用并未改善 SIM 诱导的肌肉 MDA、SOD 或 CAT 活动。我们的结果表明，EGb761 后处理逆转了 SIM 诱导的肌肉变化，可能是通过其抗氧化作用、CoQ10 水平升高和拮抗线粒体损伤。在研究期间，SIM 停用并未改善 SIM 诱导的肌肉 MDA、SOD 或 CAT 活动。我们的结果表明，EGb761 后处理逆转了 SIM 诱导的肌肉变化，可能是通过其抗氧化作用、CoQ10 水平升高和拮抗线粒体损伤。