背景:ElsholtizabodinieriVaniot,属于唇形科,在中国云南省具有重要的药用价值。传统上,它的空中部分已被用作治疗出汗的种族医学,头痛,发烧,咳嗽,咽炎,消化不良,和肝炎。然而,E.bodinieri的安全性评估仍未探索。
目的:本研究旨在研究博迪尼利(E.bodinieri)热水提取物(HEEB)的植物化学成分,Sprague-Dawley(SD)大鼠口服给药的28天亚急性和90天亚慢性毒性。
方法:用UHPLC-ESI-HRMS/MS分析HEEB的化学成分。首先,选择SD大鼠单次口服施用5000mg/kg的最大剂量以评价毒性。随后,对Sprague-Dawley(SD)大鼠进行连续28天的亚急性和90天亚慢性毒性评估,对前者重复剂量为2500、1250、625和312.5mg/kg,后者为1500、1000和500mg/kg。对于毒性评估,血液学和血清生化指标测定,收集大鼠的主要器官以计算器官系数。此外,在收集的组织上进行苏木精-伊红(H&E)染色以评估由反复口服施用HEEB诱导的组织病理学变化。
结果:通过UHPLC-ESI-HRMS/MS分析鉴定了总共23个化合物。急性毒性评估显示,在14天的时间内,口服HEEB不会导致雌性大鼠死亡和行为异常变化。表明大约致死剂量(ALD)高于5000mg/kg。在连续的28天和90天毒性评估中,2500mg/kg和1500mg/kg的HEEB剂量导致雌性和雄性大鼠的肝和肾组织损伤,这是由AST水平升高引起的,ALT,BUN,Na+,和Cl-。
结论:急性,28天亚急性和90天亚慢性毒性评估,无观察到的不良反应水平(NOAEL)被确定为1000mg/kg/天。这些发现不仅为其药用和食用应用提供了安全信息,也促进了该工厂的进一步全面发展。
BACKGROUND: Elsholtiza bodinieri Vaniot, belonging to the family Lamiaceae, has important medicinal value in Yunnan province of China. Traditionally, its aerial parts have been used as an ethnomedicine to treat diaphoresis, headache, fever, cough, pharyngitis, dyspepsia, and hepatitis. However, the safety assessment of E. bodinieri is still unexplored.
OBJECTIVE: This study aimed to investigate the phytochemical constituents of the hot water extract from E. bodinieri (HEEB) and evaluate the 14-day acute, 28-day subacute and 90-day subchronic toxicity by oral administration in Sprague-Dawley (SD) rats.
METHODS: The chemical constituents of HEEB were analyzed by UHPLC-ESI-HRMS/MS. Firstly, SD rats were chosen for a single oral administration of the maximum dose of 5000 mg/kg to evaluate toxicity. Subsequently, consecutive 28-day subacute and 90-day subchronic toxicity assessments of HEEB were conducted on Sprague-Dawley (SD) rats through repeated doses of 2500, 1250, 625, and 312.5 mg/kg for the former, and 1500, 1000, and 500 mg/kg for the latter. For toxicity evaluation, hematology and serum biochemical indicators were determined, and major organs of the rats were collected to calculate organ coefficients. Additionally, hematoxylin-eosin (H&E) staining was performed on the collected tissues to assess histopathological changes induced by repeated oral administration of HEEB.
RESULTS: A total of 23 compounds were identified by UHPLC-ESI-HRMS/MS analysis. Acute toxicity assessment revealed that oral administration of HEEB did not induce mortality and unnormal behavior changes in female rats over a 14-day period, suggesting that the approximate lethal dose (ALD) was higher than 5000 mg/kg. In consecutive 28-day and 90-day toxicity evaluations, HEEB doses of 2500 mg/kg and 1500 mg/kg resulted in hepatic and kidney tissue damage in both female and male rats, which was verified by the increased levels of AST, ALT, BUN, Na+, and Cl-.
CONCLUSIONS: After the acute, 28-day subacute and 90-day subchronic toxicity evaluation, the No Observed Adverse Effect Level (NOAEL) was determined as 1000 mg/kg/day. These findings not only provided a safety information for its medicinal and edible application, but also promoted the further comprehensive development of this plant.