Dimeric sesquiterpenoids with anti-inflammatory activities from Inula britannica.
10.1016/S1875-5364(25)60931-9
- Author:
Juan ZHANG
1
;
Jiankun YAN
2
;
Hongjun DONG
3
;
Rui ZHANG
1
;
Jing CHANG
1
;
Yanli FENG
1
;
Xinrong XU
1
;
Wei LI
4
;
Feng QIU
5
,
6
;
Chengpeng SUN
6
,
7
Author Information
1. School of Chinese Materia Medica, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
2. School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
3. Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China.
4. Faculty of Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan.
5. School of Chinese Materia Medica, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address: fengqiu20070118@
6. com.
7. School of Chinese Materia Medica, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address: suncp146@
- Publication Type:Journal Article
- Keywords:
Anti-inflammatory effects;
Inula britannica;
Keap1-Nrf2;
Mechanism;
Sesquiterpenoid dimers
- MeSH:
Mice;
Animals;
Sesquiterpenes/isolation & purification*;
Anti-Inflammatory Agents/isolation & purification*;
Inula/chemistry*;
RAW 264.7 Cells;
Nitric Oxide;
Molecular Structure;
NF-kappa B/immunology*;
NF-E2-Related Factor 2/immunology*;
Macrophages/immunology*;
Nitric Oxide Synthase Type II/immunology*;
Plant Extracts/pharmacology*;
Lipopolysaccharides;
Tumor Necrosis Factor-alpha/immunology*;
I-kappa B Kinase/genetics*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(8):961-971
- CountryChina
- Language:English
-
Abstract:
In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A-G (1-7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10-27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC50 values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L-1, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
