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Molecules 2018, 23(3), 653; https://doi.org/10.3390/molecules23030653

Identification of the NADPH Oxidase 4 Inhibiting Principle of Lycopus europaeus

1
Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria
2
Institute for Biomedical Aging Research and CMBI, University of Innsbruck, 6020 Innsbruck, Austria
3
Cura Marketing GmbH, 6020 Innsbruck, Austria
4
Institute of Botany, University of Innsbruck, 6020 Innsbruck, Austria
*
Authors to whom correspondence should be addressed.
Received: 31 January 2018 / Revised: 5 March 2018 / Accepted: 9 March 2018 / Published: 14 March 2018
(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)
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Abstract

NADPH oxidase 4 (Nox4) has recently been implicated as driving force in cellular senescence. Thus, there is growing interest to develop Nox4 inhibitors, which might be valuable agents for cosmeceutical applications. Alpine plants represent a valuable source for the identification of novel bioactive natural products with anti-ageing effects, especially substances that protect plants against UV radiation, which is also known to contribute to the ageing of human skin. Therefore, the aim of this study was to identify novel Nox4 inhibitors from alpine plants. Within an initial screening of extracts of alpine plants on their ability to inhibit Nox4 activity in HEK cells, the methanolic extract of the subaerial parts of Lycopus europaeus showed a strong inhibition of Nox4 (81% chemiluminescence quenching) and a simultaneously high cell viability (91% vitality). Rosmarinic acid was isolated and identified as the major compound in this bioactive extract. It showed a dose dependent inhibitory activity on Nox4 with an IC50 of 1 µM. Moreover, it also showed a significant inhibitory activity on Nox2 in the low micromolar range, whereas no inhibition of Nox5 was detected. Further investigations confirmed that the observed effects of rosmarinic acid on Nox2 and Nox4 are real inhibitory activities, and not due to ROS scavenging effects. Therefore, L. europaeus, which we demonstrated to be a good source of rosmarinic acid, has great potential for usage in cosmeceutical products with anti-ageing activity. View Full-Text
Keywords: Lycopus europaeus; NADPH oxidase 4; rosmarinic acid; anti-ageing; ROS Lycopus europaeus; NADPH oxidase 4; rosmarinic acid; anti-ageing; ROS
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Revoltella, S.; Baraldo, G.; Waltenberger, B.; Schwaiger, S.; Kofler, P.; Moesslacher, J.; Huber-Seidel, A.; Pagitz, K.; Kohl, R.; Jansen-Duerr, P.; Stuppner, H. Identification of the NADPH Oxidase 4 Inhibiting Principle of Lycopus europaeus. Molecules 2018, 23, 653.

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