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Planta Med 2025; 91(01/02): 29-39
DOI: 10.1055/a-2440-5166
Biological and Pharmacological Activity
Original Papers

Anti-Inflammatory Activity of Labdane and Norlabdane Diterpenoids from Leonurus sibiricus Related to Modulation of MAPKs Signaling Pathway

Nguyen Minh Trang
1   College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea
,
Le Ba Vinh 
2   Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology, Hanoi, Vietnam
,
Nguyen Viet Phong 
3   Department of Biology Education, Teachers College and Institute for Phylogenomics and Evolution, Kyungpook National University, Daegu, Republic of Korea
,
Seo Young Yang
3   Department of Biology Education, Teachers College and Institute for Phylogenomics and Evolution, Kyungpook National University, Daegu, Republic of Korea
› Author AffiliationsThis research was supported by the National Research Foundation of Korea (NRF) and funded by the Korea government (MSIT) (No. NRF- 2022R1C1 C1004636). The authors would like to thank the Institute of Chemistry, VAST, for NMR measurement services and the Institute of Marine Biochemistry, VAST, for HR-MS and ECD measurement services.
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Abstract

Leonurus sibiricus, a widely cultivated herbaceous plant in Asian countries, exhibits diverse medicinal applications. Recent studies emphasize its pharmacological properties and efficacy in promoting bone health. In addition to the known compounds and their pharmacological activities, in this study, we isolated and elucidated two new labdane-type diterpenoids, (3R,5R,6S,10S)-3,6-dihydroxy-15-ethoxy-7-oxolabden-8(9),13(14)-dien-15,16-olide (1) and (4R,5R,10S)-18-hydroxy-14,15-bisnorlabda-8-en-7,13-dione (2), a new natural phenolic compound, and a known compound from L. sibiricus using advanced spectroscopic techniques, including circular dichroism spectroscopy, high-resolution mass spectrometry, and 1- and 2-dimensional NMR. Among these, compound 1 demonstrated potent inhibition of nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA expression levels, followed by compound 2. Whereas compounds 3 and 4 did not exhibit effectiveness in RAW264.7 macrophages. Moreover, compound 1 suppressed pro-inflammatory markers induced by lipopolysaccharide (LPS) stimulation. Compound 1 also suppressed iNOS and cyclooxygenase-2 (COX-2) protein levels and downregulated pro-inflammatory cytokines. Additionally, compound 1 showed inhibition of the phosphorylation of p38, JNK, and ERK, key mediators of the MAPK signaling pathway. These findings indicate that a natural-derived product, compound 1, might be a potential candidate as an anti-inflammation mediator.

Keywords

Leonurus sibiricus - labdane diterpenoid - anti-inflammation - MAPKs

Supporting Information

    NMR and HR-MS spectra of compounds 1–3, uncropped full-length image of Western blot membrane, and the details of primer sequences are available as Supporting Information.

  • Supporting Information


Publication History

Received: 16 May 2024

Accepted after revision: 12 October 2024

Accepted Manuscript online:
12 October 2024

Article published online:
04 November 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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