title: Actions of water extract from Cordyceps militaris in hyperuricemic mice induced by potassium oxonate combined with hypoxanthine.
abstract: BACKGROUND
  Cordyceps militaris was recorded in the classic traditional Chinese medicine book with the main functions of "protecting liver and enhancing kidney functions", influencing serum uric acid levels.
  
  
  OBJECTIVE
  The aim is to investigate the hypouricemic effects and possible mechanism of C. militaris in hyperuricemic mice.
  
  
  METHODS
  A water extract (WECM) was prepared by decocting C. militaris directly at 80 °C in water bath, followed by lyophilization. WECM at 50, 100 and 200mg/kg was orally administered to hyperuricemic mice induced by potassium oxonate and hypoxanthine combinedly and allopurinol (5mg/kg) was served as a positive control.
  
  
  RESULTS
  WECM exhibited excellent hypouricemic activity, which could decrease the serum uric acid levels of the hyperuricemic mice (306μmol/L) to 189, 184 and 162μmol/L at different doses respectively (P<0.01), approaching the levels of normal mice (184μmol/L). The urate transporter 1 (URAT1) protein levels of kidney at different doses of WECM were 28.15, 17.43, 9.03pg/mL respectively, much lower than that in the hyperuricemia group (93.45pg/mL, P<0.01); and suggested WECM may interact with URAT1. Docking simulations using modeled structure of URAT1 suggested that LYS145, ARG325, ARG477 and ASP168 of URAT1 are key functional residues of URAT1. Four active compounds in C. militaris were identified and their interaction energies with target were estimated between -200 and -400kcal/mol.
  
  
  CONCLUSIONS
  These findings suggested that C. militaris produced significant hypouricemic actions and the hypouricemic effects of WECM may be attributed to the inhibitive effect of WECM on URAT1 protein levels. The results of blood urine nitrogen and serum creatinine levels and liver, kidney and spleen coefficients showed that WECM have no negative impacts on liver, renal and spleen functions. The screened four active compounds using molecular docking method deserve further investigation in other work.
authors.affiliation: State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou 510070, China; Guangdong Yuewei Edible Fungi Technology Co., Guangzhou 510663, China. Electronic address: tianqiao@mail.ustc.edu.cn.
authors.forename: Tianqiao
authors.initials: T
authors.lastname: Yong
authors.affiliation: Guangdong Yuewei Edible Fungi Technology Co., Guangzhou 510663, China.
authors.forename: Minglong
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou 510070, China.
authors.forename: Diling
authors.initials: D
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou 510070, China.
authors.forename: Ou
authors.initials: O
authors.lastname: Shuai
authors.affiliation: State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou 510070, China.
authors.forename: Shaodan
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou 510070, China.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Su
authors.affiliation: Guangdong Yuewei Edible Fungi Technology Co., Guangzhou 510663, China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Jiao
authors.affiliation: State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou 510070, China.
authors.forename: Delong
authors.initials: D
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou 510070, China; Guangdong Yuewei Edible Fungi Technology Co., Guangzhou 510663, China.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D032661:Cordyceps / Q000737:chemistry*; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D033461:Hyperuricemia / Q000139:chemically induced / Q000517:prevention & control*; D019271:Hypoxanthine / Q000008:administration & dosage / Q000009:adverse effects*; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D010936:Plant Extracts / Q000494:pharmacology*; D014867:Water
chemical_list: D010936:Plant Extracts; D014867:Water; D019271:Hypoxanthine; C489337:potassium oxonate; D010094:Oxonic Acid; D003404:Creatinine
keywords: Cordyceps militaris; Homology modelling; Hyperuricemia; Molecular docking; Urate transporter 1