title: Munronia pinnata (Wall.) Theob.: unveiling phytochemistry and dual inhibition of 5-lipoxygenase and microsomal prostaglandin E2 synthase (mPGES)-1.
abstract: BACKGROUND
  Preparations from Munronia pinnata (Wall.) Theob. are extensively used in traditional medicine in Sri Lanka for the treatment of inflammatory conditions. However, neither the pharmacological features nor the phytochemistry of this plant are explored in order to understand and rationalize the reported ethnobotanical significance. As 5-lipoxygenase (5-LO) and microsomal prostaglandin E2 synthase (mPGES)-1 are crucial enzymes in inflammatory disorders, we evaluated their inhibition by M. pinnata extracts and studied the chemical profile of the plant for the identification of relevant constituents.
  
  
  METHODS
  Cell-free and cell-based assays were employed in order to investigate the suppression of 5-LO and mPGES-1 activity. Cell viability, radical scavenger activities, and inhibition of reactive oxygen species formation (ROS) in neutrophils were studied to assess cytotoxic and antioxidant effects. Gas and liquid chromatography coupled to mass spectrometric analysis enabled the characterization of secondary metabolites.
  
  
  RESULTS
  The n-hexane extract of M. pinnata efficiently suppressed 5-LO activity in stimulated human neutrophils (IC50 =8.7µg/ml) and potently inhibited isolated human recombinant 5-LO (IC50 =0.48µg/ml) and mPGES-1 (IC50 =1.0µg/ml). In contrast, no significant radical scavenging activity or suppression of ROS formation was observed, and neutrophil viability was unaffected. The phytochemistry of the plant was unveiled for the first time and phytosterols, fatty acids, sesquiterpenes and several other types of secondary metabolites were identified.
  
  
  CONCLUSIONS
  Together, potent inhibition of 5-LO and mPGES-1 activity, without concomitant antioxidant activity and cytotoxic effects, rationalizes the ethnopharmacological use of M. pinnata as anti-inflammatory remedy. Detailed chromatographic/mass spectrometric analysis reveals discrete chemical structures of relevant constituents.
authors: Research Group Mass Spectrometry and Proteomics, Max Planck Institute for Chemical Ecology, Hans-Knoell-Strasse 8, 07745 Jena, Germany.
authors: Mayuri
authors: M
authors: Napagoda
authors: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, 07743 Jena, Germany.
authors: Jana
authors: J
authors: Gerstmeier
authors: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, 07743 Jena, Germany.
authors: Andreas
authors: A
authors: Koeberle
authors: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, 07743 Jena, Germany.
authors: Sandra
authors: S
authors: Wesely
authors: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, 07743 Jena, Germany.
authors: Sven
authors: S
authors: Popella
authors: Research Group Mass Spectrometry and Proteomics, Max Planck Institute for Chemical Ecology, Hans-Knoell-Strasse 8, 07745 Jena, Germany.
authors: Sybille
authors: S
authors: Lorenz
authors: Chair for Bioinformatics, Friedrich-Schiller-University Jena, Ernst-Abbe-Platz 2, 07743 Jena, Germany.
authors: Kerstin
authors: K
authors: Scheubert
authors: Chair for Bioinformatics, Friedrich-Schiller-University Jena, Ernst-Abbe-Platz 2, 07743 Jena, Germany.
authors: Sebastian
authors: S
authors: Böcker
authors: Research Group Mass Spectrometry and Proteomics, Max Planck Institute for Chemical Ecology, Hans-Knoell-Strasse 8, 07745 Jena, Germany. Electronic address: svatos@ice.mpg.de.
authors: Aleš
authors: A
authors: Svatoš
authors: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, 07743 Jena, Germany. Electronic address: oliver.werz@uni-jena.de.
authors: Oliver
authors: O
authors: Werz
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D029582:Meliaceae; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D000071876:Prostaglandin-E Synthases; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D001094:Arachidonate 5-Lipoxygenase; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases
keywords: 5-Lipoxygenase; Inflammation; Mass spectrometry; Microsomal prostaglandin E2 synthase-1; Munronia pinnata; Radical scavenger