Anti-inflammatory Mechanisms of Sage Explored Interview with:

PD Dr. Andreas Koeberle Lehrstuhl für Pharmazeutische/Medizinische Chemie Institut für Pharmazie Biologisch-Pharmazeutische Fakultät Friedrich-Schiller-Universität Jena Philosophenweg Jena

Dr. Koeberle

PD Dr. Andreas Koeberle
Lehrstuhl für Pharmazeutische/Medizinische Chemie Institut für Pharmazie Biologisch-Pharmazeutische Fakultät
Jena Philosophenweg Jena What is the background for this study? What are the main findings?

Response: Natural products from plants used in traditional medicine are valuable sources for identifying novel strategies as well as lead structures for drug development. The diterpenoids carnosol and carnosic acids from Salvia spp. (sage) represent such candidate compounds. They exert prominent anti-inflammatory activities though their molecular mechanisms are incompletely understood, which hampers their pharmacological use.

Our study investigated the potential of carnosol and carnosic acid in inflammatory pain and addressed the cellular consequences and the molecular interactions with key targets. We demonstrate that the two diterpenoids have anti-inflammatory and anti-nociceptive effects in established mouse models of inflammation, and describe 5-lipoxygenase and microsomal prostaglandin E2 synthase-1, two key enzymes of inflammation, as primary targets. Moreover, we characterized the functional consequences of enzyme inhibition in a cellular context and investigated structural aspects of ligand/target interactions. What should readers take away from your report?

Response: Our study provides a solid basis for the molecular mechanisms of two major ingredients of sage, which is used as spice and in traditional medicine. Understanding both the molecular basis and physiological relevance of natural products is essential to fully exploit the power of nature for human health. What recommendations do you have for future research as a result of this study?

Response: Dual inhibitors of 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 are considered as alternative to classical anti-inflammatory and analgetic drugs that inhibit cyclooxygenase isoenzymes due to reduced side effects. Despite encouraging findings from knock-out studies and enormous efforts in drug development within the last decade, only few mPGES-1 inhibitors recently entered clinical trials. By revealing 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 as key targets of carnosol and carnosic acid, our study encourages successive steps of the drug discovery process, leaded by in silico techniques and structure-activity relationship studies based on semisynthetic derivatives. Hit compounds are then to be investigated in diverse animal models of inflammation and cancer to elucidate their efficacy and safety for clinical application. We are very interested in this process and will promote and accompany further drug development efforts. Is there anything else you would like to add?

Response: Our study demonstrates the need for comprehensive, interdisciplinary approaches unraveling the complex mechanisms of natural products. Carnosol and carnosic acid have been intensively investigated during the last decades, and dozens of molecular targets have been reported. However, the relevance of many of these interactions have not been confirmed under physiological conditions, and it is unlikely that the multitude of low-affinity targets reaches effective plasma and tissue concentrations. Hence, studies in artificial test systems without considering physiological plasma concentrations might rather confuse than contribute to the understanding of the molecular mechanisms of natural products. Thank you for your contribution to the community.


n vivo and in vitro biological evaluation of the anti-inflammatory and analgesic response of carnosol and carnosic acid and in silico analysis of their target interactions.” Francesco Maione, Vincenza Cantone, Simona Pace, Maria Giovanna Chini, Angela Bisio, Giovanni Romussi, Stefano Pieretti, Oliver Werz, Andreas Koeberle, Nicola Mascolo, and Giuseppe Bifulco. British Journal of Pharmacology; Published Online: July 28, 2016 (DOI: 10.1111/bph.13545)

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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