title: NMR metabolomics for identification of adenosine A1 receptor binding compounds from Boesenbergia rotunda rhizomes extract.
abstract: BACKGROUND
  Boesenbergia rotunda Linn. (Zingiberaceae) is traditionally used in many Asian countries as medicine for stomach pain and discomfort, viral and bacterial infection, inflammation, and as diuretic agent.
  
  
  OBJECTIVE
  The study aimed to identify adenosine A1 receptor binding compounds from Boesenbergia rotunda rhizome extract by using comprehensive extraction coupled to the NMR metabolomics method.
  
  
  METHODS
  Dried and powdered Boesenbergia rotunda rhizomes were extracted with the comprehensive extraction method to obtain several fractions with different polarity. Each fraction was divided into two: for NMR analysis and for adenosine A1 receptor binding test. Orthogonal projection to the least square analysis (OPLS) was used to study the correlation between metabolites profile and adenosine A1 receptor binding activity of the plant extracts. Based on Y-related coefficient and variable of important (VIP) value, signals in active area of OPLS loading plot were studied and the respective compounds were then elucidated
  
  
  CONCLUSIONS
  Based on OPLS Y-related coefficient plot and variable of importance value plot, several characteristic signals were found to positively correlate to the binding activity. By using 1D and 2D NMR spectra of one of the most active fraction, pinocembrine and hydroxy-panduratin were identified as the possible active compounds. Two signals from ring C of pinocembrine flavanone skeleton with negative coefficient correlations possibly overlapped with those of non-active methoxylated flavanones which were also presence in the extract. NMR based metabolomics applied in this study was able to quickly identify bioactive compounds from plant extract without necessity to purify them. Further confirmation by isolating pinocembrine and hydroxy-panduratin and testing their adenosine A1 receptor binding activity to chemically validate the method are required.
  
  
  CONCLUSIONS
  Two flavonoid derivatives, pinocembrine and hydroxy-panduratin, have been elucidated as possible active compounds bind to adenosine A1 receptor. Flavonoid was reported to be one of natural antagonist ligand for adenosine A1 receptor while antagonistic activity to the receptor is known to associate with diuretic activity. Thus, the result of this research supports the traditional use of Boesenbergia rotunda rhizome extract as diuretic agent.
authors: Natural Products Laboratory, Institute of Biology, Leiden University, 2300 RA Leiden, The Netherlands; Department of Food Science and Technology, Bogor Agricultural University, IPB Darmaga Campus, PO Box 220, Bogor 16680, Indonesia; Southeast Asian Food and Agricultural Science and Technology (SEAFAST) Center, Jalan Puspa No. 1, IPB Darmaga Kampus, Bogor 16680, Indonesia. Electronic address: nancy_dewi@ipb.ac.id.
authors: Nancy Dewi
authors: ND
authors: Yuliana
authors: Slamet
authors: S
authors: Budijanto
authors: Robert
authors: R
authors: Verpoorte
authors: Young Hae
authors: YH
authors: Choi
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D010936:Plant Extracts / Q000494:pharmacology*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D027343:Rhizome; D030521:Zingiberaceae
chemical_list: D010936:Plant Extracts; D043682:Receptor, Adenosine A1
keywords: Adenosine A1 receptor; Boesenbergia rotunda; Metabolomics; NMR; OPLS