Lee Kyungjin, Kim Bumjung, Hur Heseung, Chinannai Khanita Suman, Ham Inhye, Choi Ho-Young
Department of Herbology, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
Chin J Integr Med. 2017 Dec 21. doi: 10.1007/s11655-017-2771-7.
To investigate the hypotensive and hypolipidemic effects of Modified Sanhuang Xiexin Decoction (, HVC1), a herbal prescription for the vascular diseases in Chinese medicine and evaluate the acute and subchronic oral toxicities.
Fifty-six spontaneous hypertensive rats (SHRs) were used to investigate the hypotensive and hypolipidemic effect of HVC1. Rats in the normal group (n=8) were fed with normal diet. The rats in the other groups (n=48) were fed with high fat and cholesterol diet for inducing hyperlipidemia models. Forty-eight rats were randomly divided into 6 groups [model, positive control (amlodipine, simvastain), 50, 250, and 1,000 mg/(kg•d) HVC1 groups] with 8 animals in each group. Normal and model groups were treated with distilled water [1 mL/(kg•d)], the positive control group was treated with amlodipine [5 mg/(kg•d)] or simvastatin [10 mg/(kg•d)], and the HVC1 groups were treated with HVC1 [50, 250, or 1,000 mg/(kg•d)] for 8 weeks, respectively. Blood pressure (BP) of the rats was measured using a non-invasive tail cuff system. On the last day of the experiment, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels were measured. To investigate the safety of HVC1, acute and subchronic toxicity studies were conducted on Sprague-Dawley rats. In toxicity studies, the body weight, food and water consumption of rats were measured and clinical signs observation, ophthalmologic examinations, urinalysis, hematological analysis, and serum biochemical analysis were performed.
A dose of 50 and 250 mg/(kg•d) HVC1 lowered systolic and diastolic BP (P<0.05). HVC1 at 1,000 mg/(kg•d) decreased TC, LDL-C and TG levels, respectively (P<0.01 or P<0.05) and 250 mg/(kg•d) HVC1 decreased TG levels on hyperlipidemic SHRs (P<0.05). In the acute toxicity study, oral administration of HVC1 did not show any toxicity effect, and the median lethal dose value of HVC1 was greater than 5,000 mg/kg. In the subchronic toxicity study, oral administration of HVC1 for 4 weeks also did not show any toxicity effect, and the no-observedadverse-effect-level of HVC1 was established as 2,000 mg/(kg•d).
These results could be used as preclinical data for clinical trials that develop HVC1 as a herbal medicine for treating or preventing hypertension and hyperlipidemia.
研究中药血管疾病方剂改良三黄泻心汤（HVC1）的降压和降脂作用，并评估其急性和亚慢性经口毒性。
采用56只自发性高血压大鼠（SHR）研究HVC1的降压和降脂作用。正常组（n = 8）大鼠给予正常饮食。其他组（n = 48）大鼠给予高脂高胆固醇饮食以诱导高脂血症模型。48只大鼠随机分为6组[模型组、阳性对照组（氨氯地平、辛伐他汀）、50、250和1000mg/（kg•d）HVC1组]，每组8只动物。正常组和模型组给予蒸馏水[1mL/（kg•d）]，阳性对照组给予氨氯地平[5mg/（kg•d）]或辛伐他汀[10mg/（kg•d）]，HVC1组分别给予HVC1[50、250或1000mg/（kg•d）]，持续8周。使用无创尾套系统测量大鼠血压（BP）。在实验的最后一天，测量血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯（TG）水平。为研究HVC1的安全性，对Sprague-Dawley大鼠进行急性和亚慢性毒性研究。在毒性研究中，测量大鼠的体重、食物和水消耗量，并进行临床体征观察、眼科检查、尿液分析、血液学分析和血清生化分析。
50和250mg/（kg•d）剂量的HVC1可降低收缩压和舒张压（P<0.05）。1000mg/（kg•d）的HVC1分别降低了TC、LDL-C和TG水平（P<0.01或P<0.05），250mg/（kg•d）的HVC1降低了高脂血症SHR的TG水平（P<0.05）。在急性毒性研究中，口服HVC1未显示任何毒性作用，HVC1的半数致死剂量值大于5000mg/kg。在亚慢性毒性研究中，口服HVC1 4周也未显示任何毒性作用，HVC1的未观察到不良反应水平确定为2000mg/（kg•d）。
这些结果可作为将HVC1开发为治疗或预防高血压和高脂血症的草药进行临床试验的临床前数据。
