Mayuri Napagoda1, Jana Gerstmeier2, Sandra Wesely2, Sven Popella2, Sybille Lorenz1, Kerstin Scheubert3, Aleš Svatoš4, Oliver Werz5. 1. Research Group Mass Spectrometry and Proteomics, Max Planck Institute for Chemical Ecology, Hans-Knoell-Strasse 8, D-07745 Jena, Germany. 2. Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, D-07743 Jena, Germany. 3. Chair for Bioinformatics, Friedrich-Schiller-University Jena, Ernst-Abbe-Platz 2, D-07743 Jena, Germany. 4. Research Group Mass Spectrometry and Proteomics, Max Planck Institute for Chemical Ecology, Hans-Knoell-Strasse 8, D-07745 Jena, Germany. Electronic address: svatos@ice.mpg.de. 5. Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, D-07743 Jena, Germany. Electronic address: oliver.werz@uni-jena.de.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The perennial herb Plectranthus zeylanicus Benth is extensively used in traditional medicine in Sri Lanka and South India for treating inflammatory conditions, but pharmacological features of Plectranthus zeylanicus are hardly explored in order to understand and rationalize its use in ethnomedicine. As 5-lipoxygenase (5-LO) is a key enzyme in inflammatory disorders such as asthma or atherosclerosis, we investigated 5-LO inhibition by Plectranthus zeylanicus extracts and analyzed relevant constituents. MATERIALS AND METHODS: We applied cell-free and cell-based assays to investigate suppression of 5-LO activity. Cell viability, radical scavenger activities, and inhibition of reactive oxygen species formation (ROS) in neutrophils were analysed to exclude unspecific cytotoxic or antioxidant effects. Constituents of the extracts were characterized by bioassay-guided fractionation and by analysis using gas or liquid chromatography coupled to mass spectrometric (Orbitrap) analysis. RESULTS: Extracts of Plectranthus zeylanicus prepared with n-hexane or dichloromethane potently suppressed 5-LO activity in stimulated human neutrophils (IC50=6.6 and 12µg/ml, respectively) and inhibited isolated human recombinant 5-LO (IC50=0.7 and 1.2µg/ml, respectively). In contrast, no significant radical scavenging activity or suppression of ROS formation was observed, and neutrophil viability was unaffected. Besides ubiquitously occurring ingredients, coleone P, cinncassiol A and C, and callistric acid were identified as constituents in the most active fraction. CONCLUSIONS: Together, potent inhibition of 5-LO activity, without concomitant anti-oxidant activity and cytotoxic effects, rationalizes the ethnopharmacological use of Plectranthus zeylanicus as anti-inflammatory remedy. Modern chromatographic/mass spectrometric analysis reveals discrete chemical structures of relevant constituents.
ETHNOPHARMACOLOGICAL RELEVANCE: The perennial herb Plectranthus zeylanicus Benth is extensively used in traditional medicine in Sri Lanka and South India for treating inflammatory conditions, but pharmacological features of Plectranthus zeylanicus are hardly explored in order to understand and rationalize its use in ethnomedicine. As 5-lipoxygenase (5-LO) is a key enzyme in inflammatory disorders such as asthma or atherosclerosis, we investigated 5-LO inhibition by Plectranthus zeylanicus extracts and analyzed relevant constituents. MATERIALS AND METHODS: We applied cell-free and cell-based assays to investigate suppression of 5-LO activity. Cell viability, radical scavenger activities, and inhibition of reactive oxygen species formation (ROS) in neutrophils were analysed to exclude unspecific cytotoxic or antioxidant effects. Constituents of the extracts were characterized by bioassay-guided fractionation and by analysis using gas or liquid chromatography coupled to mass spectrometric (Orbitrap) analysis. RESULTS: Extracts of Plectranthus zeylanicus prepared with n-hexane or dichloromethane potently suppressed 5-LO activity in stimulated human neutrophils (IC50=6.6 and 12µg/ml, respectively) and inhibited isolated human recombinant 5-LO (IC50=0.7 and 1.2µg/ml, respectively). In contrast, no significant radical scavenging activity or suppression of ROS formation was observed, and neutrophil viability was unaffected. Besides ubiquitously occurring ingredients, coleone P, cinncassiol A and C, and callistric acid were identified as constituents in the most active fraction. CONCLUSIONS: Together, potent inhibition of 5-LO activity, without concomitant anti-oxidant activity and cytotoxic effects, rationalizes the ethnopharmacological use of Plectranthus zeylanicus as anti-inflammatory remedy. Modern chromatographic/mass spectrometric analysis reveals discrete chemical structures of relevant constituents.
Authors: Qing Liu; Jianping Li; Adam Hartstone-Rose; Jing Wang; Jiqiang Li; Joseph S Janicki; Daping Fan Journal: Evid Based Complement Alternat Med Date: 2015-05-18 Impact factor: 2.629
Authors: Eva María Domínguez-Martín; Mariana Magalhães; Ana María Díaz-Lanza; Mário P Marques; Salvatore Princiotto; Ana M Gómez; Thomas Efferth; Célia Cabral; Patricia Rijo Journal: Molecules Date: 2022-06-14 Impact factor: 4.927