Affiliation:
1. Department of Pharmacy, Medical School, Huanghe Science and Technology College, Zhengzhou, People's Republic of China
2. State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
3. Marine Sugar Engineering Drug R & D Lab., Marine Biomedical Research Institute of Qingdao, Qingdao, People's Republic of China
Abstract
The extract of Gnaphalium affine has been reported to have antihyperuricemic and renal protective effects in vivo. The plant could alleviate acute hyperuricemia by inhibiting the activity of xanthine oxidase (XOD). 3,4,5-Tri-O-caffeoylquinic acid (3,4,5-triCQA), 4,4',6'-trihydroxy-2'-methoxychalcone (Chal), and caffeic acid (CA) were identified as the main ingredients of the plant attributed to the potential to retard XOD activity. However, whether the compounds were the effective ingredient of the plant exerting antihyperuricemic activity remained largely unknown. In this study, an experimental mouse model of hyperuricemia was induced by potassium oxonate and hypoxanthine, and orally administered with 3,4,5-triCQA (10 and 20 mg/kg/d), Chal (20 and 40 mg/kg/d), and CA (40 and 80 mg/kg/d) for 6 consecutive days, respectively. Then, serum urate levels and liver XOD activities were assessed. The liver- or kidney-to body weight ratio was calculated. Allopurinol (AP, 50 mg/kg/d) and benzbromarone (BBR, 10 mg/kg/d) were used as controls. Our data showed that there were 52.7 to 81.0% inhibitions in XOD activities in mice treated with 3,4,5-TriCQA (10 and 20 mg/kg/d), Chal (20 and 40 mg/kg/d), and CA (80 mg/kg/d), and 38.8 to 72.5% reduction in uric acid levels in mice treated with 3,4,5-TriCQA (20 mg/kg/d), Chal (20 and 40 mg/kg/d), and CA (40 and 80 mg/kg/d). A larger kidney-to-body weight ratio was observed in hyperuricemic mice and further enhanced by AP treatment. However, the increasing trend was significantly reversed by additional treatment of 3,4,5-triCQA (10 and 20 mg/kg/d) and CA (40 mg/kg/d). Given the above fundings, 3,4,5-triCQA, Chal, and CA may be the key component responsible for the in vivo activities of G. affine for urate-lowering therapy and even promising agents for the treatment of hyperuricemia.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Shanghai
Subject
General Earth and Planetary Sciences,General Environmental Science
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