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Planta Med 2020; 86(15): 1108-1117
DOI: 10.1055/a-1232-6869
Biological and Pharmacological Activity
Original Papers

A New Diterpene and Anti-inflammatory Sesquiterpene Lactones from Sigesbeckia orientalis [*]

Nora S. Engels
1   Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria
,
Barbara Gierlikowska
2   Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland
3   Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland
,
Birgit Waltenberger 
1   Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria
,
Fang-Rong Chang
4   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
5   National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan
,
Anna K. Kiss
2   Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, Poland
,
Hermann Stuppner
1   Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria
› Author AffiliationsSupported by: OeAD-GmbH PL13/2015
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Abstract

Sigesbeckia orientalis, more commonly referred to as Herba Sigesbeckiae or Xi Xian Cao in traditional Chinese medicine and hy thiêm in traditional Vietnamese medicine, is used in China and Vietnam to treat inflammatory diseases such as arthritis, rheumatism, and joint pain. In initial investigations, the dichloromethane extract from the aerial parts of S. orientalis showed distinct inhibitory effects on the release of interleukin-8 in human neutrophils. Therefore, the purpose of the present study was the phytochemical investigation of the bioactive dichloromethane extract and the in vitro analysis of the effects of the isolated compounds on interleukin-8, interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein 1 release, and surface expression of adhesion molecules (CD11a, CD11b, and CD62L) in lipopolysaccharide-stimulated human neutrophils to identify the active principle(s). The separation of the bioactive dichloromethane extract using various chromatographic techniques led to the isolation of nine compounds. Their chemical structures were elucidated from nuclear magnetic resonance and mass spectrometry data. One diterpene, 17(13 → 14)-abeo-ent-3S*,13S*,16-trihydroxystrob-8(15)-ene, was identified as a new natural product. Three germacranolide sesquiterpene lactones inhibited interleukin-8 production with IC50 values between 1.6 and 6.3 µM, respectively, and tumor necrosis factor-α production with IC50 values between 0.9 and 3.3 µM, respectively. Furthermore, they significantly inhibited interleukin-1β and monocyte chemoattractant protein 1 production and diminished the effects of lipopolysaccharide on the surface expression of the adhesion molecules CD11a, CD11b, and CD62L. These findings support the traditional use of S. orientalis in the treatment of inflammatory diseases.

Key words

Sigesbeckia orientalis - Asteraceae - inflammation - neutrophils - diterpenoids - sesquiterpene lactones

* Dedicated to Professor Dr. Wolfgang Kubelka on the occasion of his 85th birthday.


Supporting Information

    IL-8 inhibitory activity of extracts and fractions, 1H and 13C NMR spectra and NOESY correlations of 1, potential cytotoxicity of 1–9, dose-activity dependence of 2–4 in the performed pharmacological assays, data on the L-cysteine methyl ester binding test, the gradient system used for the separation of the DCM extract, and the isolation procedure for 2–9 are available as Supporting Information.

  • Supporting Information


Publication History

Received: 15 January 2020

Accepted after revision: 27 July 2020

Article published online:
21 September 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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