title: Arctigenic acid, the key substance responsible for the hypoglycemic activity of Fructus Arctii.
abstract: We have reported the antidiabetic activity of the total lignans from Fructus arctii (TLFA) against alloxan-induced diabetes in mice and rats. In this study, arctigenic acid was found to be the main metabolite in rat plasma detected by UPLC/MS and HPLC/MS/MS after oral administration of TLFA. For the first time, its hypoglycemic activity and acute oral toxicity were evaluated in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and ICR mice respectively. GK rats were orally given arctigenic acid (50 mg/kg) twice daily before each meal for 12 weeks. The treatment reduced the elevated plasma glucose, glycosylated hemoglobin and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. We found that the hypoglycemic effect of arctigenic acid was partly due to the stimulation on insulin secretion, whereas the body weight was not affected by arctigenic acid administration in GK rats. Meanwhile, there was no observable acute toxicity of arctigenic acid treatment at the dosage of 280 mg/kg body weight daily in the acute 14-day toxicity study in mice. This study demonstrates that arctigenic acid may be the main metabolite in the rat serum after oral administration of TLFA, which showed significant hypoglycemic effect in GK rats, and low acute toxicity in ICR mice. The result prompts us that arctigenic acid is the key substance responsible for Fructus Arctii antidiabetic activity and it has a great potential to be further developed as a novel therapeutic agent for diabetes in humans.
authors: Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: lntcmx@163.com.
authors: Zhaohui
authors: Z
authors: Xu
authors: Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Chenchen
authors: C
authors: Gu
authors: Center for Drug Safety Evaluation, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Kai
authors: K
authors: Wang
authors: Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Jiaxing
authors: J
authors: Ju
authors: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Haiying
authors: H
authors: Wang
authors: Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Kefeng
authors: K
authors: Ruan
authors: Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Yi
authors: Y
authors: Feng
mesh_terms: D000818:Animals; D031170:Arctium / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005260:Female; D005638:Fruit / Q000737:chemistry; D005663:Furans / Q000097:blood / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D017705:Lignans / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry; D023382:Toxicity Tests, Acute
chemical_list: D005663:Furans; D005947:Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D017705:Lignans; C000596351:arctigenic acid; C071942:arctigenin
keywords: Acute oral toxicity; Arctigenic acid; Diabetes; Fructus Arctii; GK rats; Hypoglycemic activity