Lili Wang1, Zhiqiang Li2, Lin Li1, Yanlin Li1, Meng Yu1, Yunfeng Zhou3, Xinyong Lv4, Hiderori Arai5, Yang Xu6. 1. Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. 2. Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; Kanion Pharmaceutical Co., Ltd., Lianyungang 222002, China. 3. Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; Pharmaceutical College of Henan University, Kaifeng 475001, China. 4. Kanion Pharmaceutical Co., Ltd., Lianyungang 222002, China. 5. Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. 6. Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. Electronic address: vascular888@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Cortex Dictamni is used in Chinese folk medicine for the treatment of jaundice, cough, rheumatism and some skin diseases; however, its possible toxicity has not been rigorously studied. The present investigation was carried out to evaluate the safety of Cortex Dictamni aqueous extract (CDAE) by acute and sub-chronic toxicity studies. MATERIALS AND METHODS: In acute toxicity tests, seven groups of mice (n=5/group/sex) were orally treated with doses of 0, 28.7, 33.6, 39.7, 46.7, 54.9 and 64.6g/kg of CDAE and general behavior, adverse effects and mortality were recorded for up to 14 days. In sub-chronic toxicity assays, animals received CDAE by gavage at the doses of 0, 3.0, 6.0 or 12.0g/kg/day (n=10/group/sex) for 4 weeks and then followed for a 2-week recovery period. The biochemical, hematological and morphological parameters were determined. RESULTS: In adult mice, single oral administrations of CDAE (0-64.6g/kg body weight) induced an increase in the incidence of general behavioral adverse effects. The mortality rate also increased with increasing dosage (LD50=48.2g/kg). In rats, daily single oral doses of CDAE were well tolerated behaviorally after 4 weeks and induced no significant changes in body weights. However, the absolute and relative liver weight at the end of both administration and recovery periods were significantly elevated, although the histological examination of various organs revealed no differences between the control and the treated groups. The hematological and biochemical parameters were significantly changed; lymphocytes, alanine transaminase, alkaline phosphatase levels showed a significant decrease while neutrophilic granulocyte, albumin, total cholesterol, glucose and blood urea nitrogen levels showed a significant increase, suggesting disturbances of hematopoiesis and liver and kidney functions. CONCLUSIONS: Overall, the acute toxicity of CDAE was not clearly observed. However, it is possible that CDAE has a selective toxicity considering the changes in some hematological and liver function parameters and the liver-body weight ratios in the sub-chronic oral toxicity study.
ETHNOPHARMACOLOGICAL RELEVANCE: Cortex Dictamni is used in Chinese folk medicine for the treatment of jaundice, cough, rheumatism and some skin diseases; however, its possible toxicity has not been rigorously studied. The present investigation was carried out to evaluate the safety of Cortex Dictamni aqueous extract (CDAE) by acute and sub-chronic toxicity studies. MATERIALS AND METHODS: In acute toxicity tests, seven groups of mice (n=5/group/sex) were orally treated with doses of 0, 28.7, 33.6, 39.7, 46.7, 54.9 and 64.6g/kg of CDAE and general behavior, adverse effects and mortality were recorded for up to 14 days. In sub-chronic toxicity assays, animals received CDAE by gavage at the doses of 0, 3.0, 6.0 or 12.0g/kg/day (n=10/group/sex) for 4 weeks and then followed for a 2-week recovery period. The biochemical, hematological and morphological parameters were determined. RESULTS: In adult mice, single oral administrations of CDAE (0-64.6g/kg body weight) induced an increase in the incidence of general behavioral adverse effects. The mortality rate also increased with increasing dosage (LD50=48.2g/kg). In rats, daily single oral doses of CDAE were well tolerated behaviorally after 4 weeks and induced no significant changes in body weights. However, the absolute and relative liver weight at the end of both administration and recovery periods were significantly elevated, although the histological examination of various organs revealed no differences between the control and the treated groups. The hematological and biochemical parameters were significantly changed; lymphocytes, alanine transaminase, alkaline phosphatase levels showed a significant decrease while neutrophilic granulocyte, albumin, total cholesterol, glucose and blood ureanitrogen levels showed a significant increase, suggesting disturbances of hematopoiesis and liver and kidney functions. CONCLUSIONS: Overall, the acute toxicity of CDAE was not clearly observed. However, it is possible that CDAE has a selective toxicity considering the changes in some hematological and liver function parameters and the liver-body weight ratios in the sub-chronic oral toxicity study.
Authors: N S Njinga; A T Kola-Mustapha; A L Quadri; O Atolani; R O Ayanniyi; M O Buhari; T O Amusa; E O Ajani; O O Folaranmi; M T Bakare-Odunola; L Kambizi; A T Oladiji; P Ebong Journal: Heliyon Date: 2020-09-21
Authors: Miranda Sin-Man Tsang; Pang-Chui Shaw; Ida Miu-Ting Chu; Ling Cheng; Eric Chun-Wai Wong; David Tai-Wai Lau; Christopher Wai-Kei Lam; Chun-Kwok Wong Journal: Molecules Date: 2019-08-08 Impact factor: 4.411