title: Antioxidative phytochemicals from Rhododendron oldhamii Maxim. leaf extracts reduce serum uric acid levels in potassium oxonate-induced hyperuricemic mice.
abstract: BACKGROUND
  Some of the genus Rhododendron was used in traditional medicine for arthritis, acute and chronic bronchitis, asthma, pain, inflammation, rheumatism, hypertension and metabolic diseases and many species of the genus Rhododendron contain a large number of phenolic compounds and antioxidant properties that could be developed into pharmaceutical products.
  
  
  METHODS
  In this study, the antioxidative phytochemicals of Rhododendron oldhamii Maxim. leaves were detected by an online HPLC-DPPH method. In addition, the anti-hyperuricemic effect of the active phytochemicals from R. oldhamii leaf extracts was investigated using potassium oxonate (PO)-induced acute hyperuricemia.
  
  
  RESULTS
  Six phytochemicals, including (2R, 3R)-epicatechin (1), (2R, 3R)-taxifolin (2), (2R, 3R)-astilbin (3), hyposide (4), guaijaverin (5), and quercitrin (6), were isolated using the developed screening method. Of these, compounds 3, 4, 5, and 6 were found to be major bioactive phytochemicals, and their contents were determined to be 130.8 ± 10.9, 105.5 ± 8.5, 104.1 ± 4.7, and 108.6 ± 4.0 mg per gram of EtOAc fraction, respectively. In addition, the four major bioactive phytochemicals at the same dosage (100 mmol/kg) were administered to the abdominal cavity of potassium oxonate (PO)-induced hyperuricemic mice, and the serum uric acid level was measured after 3 h of administration. H&E staining showed that PO-induced kidney injury caused renal tubular epithelium nuclear condensation in the cortex areas or the appearance of numerous hyaline casts in the medulla areas; treatment with 100 mmol/kg of EtOAc fraction, (2R, 3R)-astilbin, hyposide, guaijaverin, and quercitrin significantly reduced kidney injury. In addition, the serum uric acid level was significantly suppressed by 54.1, 35.1, 56.3, 56.3, and 53.2 %, respectively, by the administrations of 100 mmol/kg EtOAc fraction and the derived major phytochemicals, (2R, 3R)-astilbin, hyposide, guaijaverin, and quercitrin, compared to the PO group. The administration of 10 mg/kg benzbromarone, a well-known uricosuric agent, significantly reduced the serum uric acid level by 45.5 % compared to the PO group.
  
  
  CONCLUSIONS
  The in vivo decrease in uric acid was consistent with free radical scavenging activity, indicating that the major phytochemicals of R. oldhamii leave extracts and the derived phytochemicals possess potent hypouricemic effects, and they could be potential candidates for new hypouricemic agents.
authors.affiliation: Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan, 333, Taiwan.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Tung
authors.affiliation: Department of Forestry and Natural Resources, National Chiayi University, Chiayi, 600, Taiwan.
authors.forename: Lei-Chen
authors.initials: LC
authors.lastname: Lin
authors.affiliation: Department of Forestry, National Chung Hsing University, Taichung, 402, Taiwan.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Forestry, National Chung Hsing University, Taichung, 402, Taiwan.
authors.forename: Shang-Tse
authors.initials: ST
authors.lastname: Ho
authors.affiliation: Department of Forestry, National Chung Hsing University, Taichung, 402, Taiwan.
authors.forename: Chi-Yang
authors.initials: CY
authors.lastname: Lin
authors.affiliation: National Laboratory Animal Center, National Applied Research Laboratories, Taipei, 11529, Taiwan.
authors.forename: Hsiao-Li
authors.initials: HL
authors.lastname: Chuang
authors.affiliation: Division of Animal Resource, Animal Technology Laboratories, Agricultural Technology Research Institute, Hsinchu City, 30093, Taiwan.
authors.forename: Chien-Chao
authors.initials: CC
authors.lastname: Chiu
authors.affiliation: Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan, 333, Taiwan. d301090007@gmail.com.
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Forestry, National Chung Hsing University, Taichung, 402, Taiwan. eric@nchu.edu.tw.
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Wu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006074:Gout Suppressants / Q000494:pharmacology / Q000627:therapeutic use*; D033461:Hyperuricemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010094:Oxonic Acid / Q000009:adverse effects; D064209:Phytochemicals / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry; D029793:Rhododendron / Q000737:chemistry; D014527:Uric Acid / Q000097:blood*
chemical_list: D000975:Antioxidants; D006074:Gout Suppressants; D064209:Phytochemicals; D010936:Plant Extracts; D014527:Uric Acid; C489337:potassium oxonate; D010094:Oxonic Acid