College of Food Science and Engineering, Kunming University of Science and Technology, Yunnan, 650504, China.
Application Technology of Biological Control for Tobacco Diseases and Insect Pests Engineering Research Center of China Tobacco, Yunnan Tobacco Company, Yuxi Branch, Yuxi, 653100, Yunnan, China.
J Ethnopharmacol. 2024 Dec 5;335:118635. doi: 10.1016/j.jep.2024.118635. Epub 2024 Jul 27.
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.
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.
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.
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.
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.
Elsholtizia bodinieri Vaniot，属于唇形科，在中国云南省具有重要的药用价值。传统上，其地上部分被用作民族药物治疗出汗、头痛、发热、咳嗽、咽炎、消化不良和肝炎。然而，E. bodinieri 的安全性评估仍未得到探索。
本研究旨在探讨 Elsholtizia bodinieri（HEEB）热水提取物的化学成分，并通过口服给药在 Sprague-Dawley（SD）大鼠中评估其 14 天急性、28 天亚急性和 90 天亚慢性毒性。
采用 UHPLC-ESI-HRMS/MS 分析 HEEB 的化学成分。首先，选择 SD 大鼠进行单次口服最大剂量 5000mg/kg，以评估毒性。随后，对 Sprague-Dawley（SD）大鼠进行连续 28 天亚急性和 90 天亚慢性毒性评估，前者给予 2500、1250、625 和 312.5mg/kg 的重复剂量，后者给予 1500、1000 和 500mg/kg 的重复剂量。对于毒性评估，测定血液学和血清生化指标，并收集大鼠的主要器官计算器官系数。此外，对收集的组织进行苏木精-伊红（H&E）染色，以评估重复口服 HEEB 引起的组织病理学变化。
通过 UHPLC-ESI-HRMS/MS 分析鉴定出 23 种化合物。急性毒性评估表明，在 14 天内，雌鼠口服 HEEB 未引起死亡和异常行为改变，提示近似致死剂量（ALD）高于 5000mg/kg。在连续 28 天和 90 天的毒性评估中，2500mg/kg 和 1500mg/kg 的 HEEB 剂量导致雌、雄大鼠的肝、肾组织损伤，AST、ALT、BUN、Na 和 Cl 的升高证实了这一点。
在急性、28 天亚急性和 90 天亚慢性毒性评估后，确定无观察不良效应水平（NOAEL）为 1000mg/kg/天。这些发现不仅为其药用和食用应用提供了安全性信息，也促进了该植物的进一步综合开发。
