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DOI: 10.1055/a-2440-5166
Anti-Inflammatory Activity of Labdane and Norlabdane Diterpenoids from Leonurus sibiricus Related to Modulation of MAPKs Signaling Pathway
This 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.

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.
Supporting Information
- 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.
Publication History
Received: 16 May 2024
Accepted after revision: 12 October 2024
Accepted Manuscript online:
12 October 2024
Article published online:
04 November 2024
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