首页|期刊导航|世界中医药杂志（英文版）|Safety Assessment of Aconitum-Derived Bulleyaconitine A: A 91-Day Oral Toxicity Study and a Tissue Accumulation Study in Rats
世界中医药杂志（英文版）2021，Vol.7Issue(2)：217-226,10.DOI:10.4103/wjtcm.wjtcm_77_20
Safety Assessment of Aconitum-Derived Bulleyaconitine A: A 91-Day Oral Toxicity Study and a Tissue Accumulation Study in Rats
Safety Assessment of Aconitum?Derived Bulleyaconitine A: A 91?Day Oral Toxicity Study and a Tissue Accumulation Study in Rats
摘要
Abstract
Background: Bulleyaconitine A (BLA) is a diterpenoid alkaloid from the rhizomes of Aconitum bulleyanum Diels and has been clinically used for chronic pain treatment in China for many years. However, the newly reported adverse events of BLA indicated that BLA still has potential safety issues. Materials and Methods: To assess the safety of BLA, analgesic tests, acute toxicity studies, repeated?dose oral toxicity studies, and tissue distribution studies after single and repeated administration of BLA were carried out. Results: Administration of 0.14 mg/kg BLA showed potent analgesic effects in both analgesic tests. In acute toxicity study, the LD50 value of BLA was calculated to be 3.4434 mg/kg. In the subchronic toxicity study, the no observed adverse effect level was 0.25 mg/kg, and the lowest observed adverse effect level was 0.5 mg/kg. The spleen, liver, and kidneys are newly identified target organs of BLA toxicity after long?term administration. Moreover, unlike a single BLA administration, repeated administration showed BLA redistribution from organs with an abundant blood supply to immune and metabolic organs. Conclusions: These results suggested that BLA itself would be nontoxic at a dosage of 0.25 mg/kg in rats and should be carefully used when combining BLA with medications that can cause spleen, liver, or kidney injury.关键词
Adverse reaction/bulleyaconitine A/repeated‑dose (91‑day) toxicity/tissue distributionKey words
Adverse reaction/bulleyaconitine A/repeated‑dose (91‑day) toxicity/tissue distribution引用本文复制引用
Shi-Liang Yin,Peter Breslin,Chun-Fu Wu,Hong Zhang,Feng Xu,Hao Wu,Fei Li,Ge Jin,Zu-Qian Wu,Ran Meng,Si-Man Ma,Fan Zhou..Safety Assessment of Aconitum-Derived Bulleyaconitine A: A 91-Day Oral Toxicity Study and a Tissue Accumulation Study in Rats[J].世界中医药杂志（英文版）,2021,7(2):217-226,10.基金项目
This work was supported by Liao Ning Education Office(No.2019 LQN10)and Shenyang Young and middle?aged science and technology innovation program(RC180308).The author also wishes to thank Professor Bo Yuan for giving us advice on HPLC?MS/MS analysis. （No.2019 LQN10）
