title: 5,7-dihydroxy-3,4,6-trimethoxyflavone attenuates ischemic damage and apoptosis in mouse islets.
abstract: BACKGROUND
  The transplantation of isolated pancreatic islets is a promising treatment for diabetes. 5,7-dihydroxy-3,4,6-trimethoxyflavone (Eupatilin), a pharmacologically active flavone derived from the Artemisia plant species, has been reported to have antioxidant and anti-inflammatory activities. This study examines the hypothesis that preoperative eupatilin treatment can attenuate ischemic damage and apoptosis before islet transplantation.
  
  
  METHODS
  Islets isolated from Balb/c mice were randomly divided into 2 groups, and cultured in medium supplemented with or without eupatilin. In vitro islet viability and function were assessed. After treatment with a cytokine cocktail consisting of tumor necrosis factor (TNF)-α, interferon (INF)-γ, and interleukin (IL)-1β, islet cell viability, function, and apoptotic status were determined. The glutathione (GSH) and nitrous oxide (NO) levels were also measured. Proteins related to apoptosis were analyzed using Western blotting.
  
  
  RESULTS
  There was no difference in cell viability between the 2 groups. Islets cultured in the medium supplemented with eupatilin showed 1.4-fold higher glucose-induced insulin secretion than the islets cultured in the medium without eupatilin. After treatment with a cytokine cocktail, glucose-induced insulin release and the total insulin content of the islets were significantly improved in eupatilin-pretreated islets compared with islets not treated with eupatilin. Apoptosis was significantly decreased, and GSH levels were elevated in the eupatilin-pretreated group. Cytokine-only treated islets produced significantly higher levels of NO, iNOS, and caspase-3 than islets pretreated with eupatilin before cytokine treatment.
  
  
  CONCLUSIONS
  These results suggest that preoperative eupatilin administration enhances islet function before transplantation and attenuates the cytokine-induced damage associated with NO production and apoptosis.
authors.affiliation: Department of Internal Medicine, Ulsan University College of Medicine, Gangneung Asan Hospital, South Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Anesthesia and Pain, Ulsan University College of Medicine, Gangneung Asan Hospital, South Korea.
authors.forename: S S
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Surgery, Ulsan University College of Medicine, Gangneung Asan Hospital, South Korea. Electronic address: jhj@gnah.co.kr.
authors.forename: H J
authors.initials: HJ
authors.lastname: Jang
authors.affiliation: Department of Surgery, Ulsan University College of Medicine, Gangneung Asan Hospital, South Korea.
authors.forename: M Y
authors.initials: MY
authors.lastname: Oh
authors.affiliation: Department of Surgery, Ulsan University College of Medicine, Gangneung Asan Hospital, South Korea.
authors.forename: D H
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Ulsan University College of Medicine, Gangneung Asan Hospital, South Korea.
authors.forename: D W
authors.initials: DW
authors.lastname: Eom
authors.affiliation: College of Korean Medicine, Gachon University, Seongnam, South Korea.
authors.forename: K S
authors.initials: KS
authors.lastname: Kang
authors.affiliation: Natural Medicine Center, Korea Institute of Science and Technology (KIST), Gangneung, South Korea.
authors.forename: S N
authors.initials: SN
authors.lastname: Kim
authors.affiliation: Natural Medicine Center, Korea Institute of Science and Technology (KIST), Gangneung, South Korea.
authors.forename: H C
authors.initials: HC
authors.lastname: Kwan
authors.affiliation: Natural Medicine Center, Korea Institute of Science and Technology (KIST), Gangneung, South Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Ham
authors.affiliation: Department of Internal Medicine, Ulsan University College of Medicine, Gangneung Asan Hospital, South Korea.
authors.forename: W J
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, South Korea.
authors.forename: D S
authors.initials: DS
authors.lastname: Jang
authors.affiliation: Asan Medical Center, Seoul, South Korea.
authors.forename: D J
authors.initials: DJ
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D004365:Drugs, Chinese Herbal; D005419:Flavonoids; C045325:eupatilin