Acute and chronic toxicity in Sprague–Dawley rats of orally-administered total lignans from Arctii Fructus, a potential therapeutic drug for diabetes

• Published in: Regulatory toxicology and pharmacology Vol. 146; p. 105542
• Main Authors: Mei, Jinwang, Li, Xiaobo, Xu, Zhiyong, Zhao, Haiyang, Zhang, Jingyun, Xu, Qin, Xu, Zhaohui
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2024
• Subjects: Acute toxicity; Chronic toxicity; Diabetes; Neurotoxic effects; NOAEL; Total lignans from Arctii Fructus; Total lignans from Arctii Fructus; Neurotoxic effects; Chronic toxicity; Diabetes; NOAEL; Acute toxicity
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2023.105542

Arctii Fructus is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is in the Chinese pharmacopoeia. Previous research showed that the total lignans from Arctii Fructus (TLAF) have pharmacological activities related to diabetes. This study evaluated the acute and chronic (26 weeks) toxicities associated with oral daily administration of TLAF in Sprague–Dawley (SD) rats. An acute-toxicity test showed that TLAF caused 10% mortality at 3,000 mg/kg × 2 (6-h interval), with toxic symptoms, such as dyspnea and tonic convulsions, indicating potential neurotoxicity. A chronic-toxicity study showed no mortality after administration. The no observed adverse-effect level was 1,800 mg/kg (approximately 54 times higher than the human clinical dose) for 26 weeks of TLAF oral administration in SD rats, with toxicity signs of excessive oral and nasal secretions and moist circumferential hair that recovered after TLAF discontinuation. In the toxicokinetic study, the two main components of TLAF, arctigenin plasma level was positively correlated with dose and tended to accumulate after multiple doses. At 1,800 mg/kg, arctiin plasma level increased and tended to accumulate after multiple doses. These results indicated that TLFA has relatively low toxicity and the potential for clinical treatment of diabetes. •The total lignans from Arctii Fructus (TLAF) is a product with stable quality.•TLAF have pharmacological activities related to diabetes and its complications.•TLFA could cause 10% mortality in SD rats in an acute toxicity test.•The NOAEL was 1,800 mg/kg for 26 weeks of TLAF oral administration in SD rats.•Toxicokinetic characteristics of TLAF were studied through arctiin and arctigenin.