Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea.
Clinical Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea.
J Ethnopharmacol. 2018 Oct 5;224:441-450. doi: 10.1016/j.jep.2018.06.017. Epub 2018 Jun 18.
Traditional herbal formula Gyejibokryeong-hwan (GJBRH; Guizhifuling-wan, Keishibukuryo-gan) consisting five medicinal herbs has been used to treat uterine disorders, gynecological diseases and blood stasis syndrome in Asia.
We evaluated the safety of GJBRH in Crl:CD Sprague-Dawley (SD) rats over a period of 13 weeks.
To confirm the stability of the components of GJBRH, we analyzed the component contents in GJBRH at different storage periods, using high-performance liquid chromatography. Male and female SD rats were orally administered with GJBRH at doses of 0, 1000, 2000 and 5000 mg/kg/day for 13 weeks and assessed after a 4-week recovery period. Mortality, changes in body weight and food consumption, organ weights, hematology and serum biochemistry were monitored during the experimental period, along with clinical observations, ophthalmological examinations, urinalysis and histopathology.
There were no significant differences among the eight marker compounds in GJBRH according to storage period. No significant GJBRH-treatment-related toxicological changes were observed in mortality or ophthalmological examinations in either sex. However, soft feces were observed in the male 5000 mg/kg/day group. In addition, there were significant changes in body weight and food consumption in both male and female rats treated with GJBRH at a dose of 5000 mg/kg/day. In the hematological examinations, we found a significant increase in white blood cells, neutrophils and fibrinogen in the 5000 mg/kg/day groups. In the urinalysis, a decrease in the total protein and albumin and an increase in the ovalbumin/globulin ratio were observed in both male and female rats treated with GJBRH at a dose of 5000 mg/kg/day. Histopathological examinations revealed erosion/ulcers and dilated glands in the stomachs of males from the 5000 mg/kg/day group, and squamous cell hyperplasia and epithelial atrophy was observed in the stomachs of both male and female rats treated with GJBRH at a dose of 5000 mg/kg/day.
The no-observed-adverse-effect level (NOAEL) was 2000 mg/kg/day for both sexes.
由五种草药组成的传统草药配方 Gyejibokryeong-hwan（GJBRH；Guizhifuling-wan，Keishibukuryo-gan）在亚洲一直被用于治疗子宫疾病、妇科疾病和血瘀综合征。
我们在 13 周的时间内评估了 GJBRH 在 Crl：CD 斯普拉格-道利（SD）大鼠中的安全性。
为了确认 GJBRH 成分的稳定性，我们使用高效液相色谱法分析了不同储存期 GJBRH 的成分含量。雄性和雌性 SD 大鼠分别以 0、1000、2000 和 5000mg/kg/天的剂量口服 GJBRH，在 4 周恢复期后进行评估。在实验期间监测死亡率、体重和食物摄入量变化、器官重量、血液学和血清生化学，以及临床观察、眼科检查、尿液分析和组织病理学检查。
根据储存期，GJBRH 中的八种标记化合物没有显著差异。在雄性和雌性中，死亡率或眼科检查均未观察到与 GJBRH 治疗相关的毒性变化。然而，雄性 5000mg/kg/天组出现软便。此外，雄性和雌性大鼠 5000mg/kg/天组体重和食物摄入量均有显著变化。在血液学检查中，我们发现白细胞、中性粒细胞和纤维蛋白原在 5000mg/kg/天组中显著增加。在尿液分析中，雄性和雌性大鼠 5000mg/kg/天组的总蛋白和白蛋白减少，卵白蛋白/球蛋白比值增加。组织病理学检查显示，雄性 5000mg/kg/天组的胃出现糜烂/溃疡和腺体扩张，雄性和雌性大鼠 5000mg/kg/天组的胃出现鳞状细胞增生和上皮萎缩。
雌雄两性的无观察不良效应水平（NOAEL）为 2000mg/kg/天。
