title: The first cyclomegastigmane rhododendroside A from Rhododendron brachycarpum alleviates HMGB1-induced sepsis.
abstract: BACKGROUND
  Endangered plant species are a vital resource for exploring novel drug prototypes. A Korean endangered plant Rhododendron brachycarpum G. Don is a broad-leaved shrub native to northern Korea and central Japan. The high mobility group box 1 protein (HMGB1) could be a specific target for the discovery of novel antiseptic agents.
  
  
  METHODS
  Gauge-invariant atomic orbital (GIAO) NMR chemical shift calculations were applied for investigation of stereochemical details with accuracy improved by application of DP4 analysis. In vitro antiseptic mechanisms were investigated utilizing immunofluorescence staining, ELISA and cell-cell adhesion assay. Cecal ligation and puncture (CLP) operation was employed to evaluate in vivo potential alleviating severe sepsis and septic shock.
  
  
  RESULTS
  The first bicyclic megastigmane glucoside rhododendroside A (1) along with known megastigmane glucosides (2-5) were isolated from the leaves of R. brachycarpum. The structure of 1 was established by NMR analysis as well as comparison of the experimental chemical shifts with those of computed values employing DP4 application. In the CLP operation model that simulates severe sepsis, rhododendroside A (1) improved the survival rate up to 60%.
  
  
  CONCLUSIONS
  Our results exhibit that R. brachycarpum may produce a unique scaffold that is developed into a drug lead mitigating HMGB1-induced vascular pro-inflammatory stimuli and thus alleviating severe sepsis and related manifestations.
  
  
  CONCLUSIONS
  Discovery of new drug leads would warrant conservation efforts of endangered species.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Republic of Korea; College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
authors.forename: Joonseok
authors.initials: J
authors.lastname: Oh
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 and 700-422, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 702-701 and 700-422, Republic of Korea.
authors.forename: Lee
authors.initials: L
authors.lastname: Wonhwa
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 and 700-422, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Kwak
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: National Center for Natural Products Research, The University of Mississippi, University, MS 38677, USA.
authors.forename: Amar G
authors.initials: AG
authors.lastname: Chittiboyina
authors.affiliation: Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
authors.forename: Daneel
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Hamann
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Republic of Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 and 700-422, Republic of Korea. Electronic address: baejs@knu.ac.kr.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: mkna@cnu.ac.kr.
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003512:Cyclohexanones / Q000627:therapeutic use*; D055808:Drug Discovery; D005960:Glucosides / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D045792:Norisoprenoids / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D029793:Rhododendron / Q000737:chemistry*; D018805:Sepsis / Q000188:drug therapy*
chemical_list: D003512:Cyclohexanones; D005960:Glucosides; D024243:HMGB1 Protein; D045792:Norisoprenoids; C000589206:rhododendroside A
keywords: Endangered species; High mobility group box 1 protein; Nuclear magnetic resonance chemical shift calculations; Rhododendron brachycarpum; Sepsis