Pharmacokinetic Profile and Evaluation of Acute and Subchronic Oral Toxicity of Shikimic Acid in Mice

作者：Liu-Yan Liang, Ting-Yin Lu, Long-Gen Zhong, Wenhui Su, Ziqi Ren, Meng-Ting Tao, Jian Sun, Xiao‐Ping Liao, Donghao Zhao, Yu‐Feng Zhou · 发表于：ACS Omega · 年份：2025 · DOI：10.1021/acsomega.5c03740 · 被引用次数：5 · 研究领域：Biochemical effects in animals、Tryptophan and brain disorders、Cannabis and Cannabinoid Research

High Resolution Image Download MS PowerPoint Slide Shikimic acid, a widely known hydroaromatic compound abundantly found in Illicium verum (commonly known as Chinese star anise), serves as a key intermediate in the synthesis of neuraminidase inhibitors such as oseltamivir. However, its pharmacokinetic (PK) properties and long-term safety profile remain inadequately characterized. This study systematically evaluated its PK behavior following both oral and intravenous administrations, along with its acute toxicity and 28-day subchronic oral toxicity in mice. PK analysis for shikimic acid demonstrated linear and dose-proportional behavior within the intravenous dose range of 4–16 mg/kg. Shikimic acid was rapidly eliminated from plasma, with a short terminal half-life ( T 1/2 ) of 0.76–0.85 h. Despite rapid absorption ( T max, 0.95–1.25 h) following oral administration, a low bioavailability ranging from 11.09 to 20.44% was observed in mice. Acute toxicity testing showed no mortality at oral doses of up to 10,000 mg/kg. In the 28-day subchronic oral toxicity study, mice fed diets containing high (50 g/kg), medium (16.67 g/kg), or low (5.56 g/kg) doses of shikimic acid exhibited no mortality. Hematological assessments revealed slight elevations in neutrophil counts, eosinophil counts, and hematocrit levels in the high-dose group compared to controls. Notably, a significant reduction in triglyceride levels was observed in the high-dose group, suggesting potential hypolipidemic effe...