Isosteroid alkaloids with different chemical structures from Fritillariae cirrhosae bulbus alleviate LPS-induced inflammatory response in RAW 264.7 cells by MAPK signaling pathway

• Published in: International immunopharmacology 2020-01, Vol.78, p.106047-106047, Article 106047
• Main Authors: Liu, Simei, Yang, Tiechui, Ming, Tse Wai, Gaun, Tse Kathy Wai, Zhou, Ting, Wang, Shu, Ye, Bengui
• Format: Article
• Language: English
• Subjects: Alkaloids; Anti-inflammatory; Anti-inflammatory agents; Asthma; c-Jun protein; Cytokines; Extracellular signal-regulated kinase; Fritillariae Cirrhosae Bulbus; Inflammatory diseases; Inflammatory mediators; Inflammatory response; Interleukin 6; Isosteroid alkaloids; JNK protein; Kinases; Lipopolysaccharides; Macrophages; MAP kinase; Medical treatment; Mitogen activated protein kinases; mRNA; Natural products; Nitric oxide; Organic chemistry; Phosphorylation; Proteins; Reagents; Signal transduction; Signaling; Transcription factors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Western blotting
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.106047

[Display omitted] •The anti-flammatory activity and underlying mechanism of imperialine (A), verticinone (B), verticine (C), delavine (D) and peimisine (E) were investigated for the first time.•The five isosteroid alkaloids from Fritillariae Cirrhosae Bulbus all inhibited the production of inflammatory meditators and suppressed the TNF-α and IL-6 mRNA levels on LPS-stimulated RAW 264.7 macrophages.•The phosphorylation of MAPKs signaling pathway was downregulated by the five isosteroid alkaloids.•The important differences of the structure-activity relationships for five isosteroid alkaloids were preliminarily elucidated. Isosteroid alkaloids, natural products from Fritillariae Cirrhosae Bulbus, are well known for its antitussive, expectorant, anti-asthmatic and anti-inflammatory properties. However, the anti-inflammatory effect and its mechanism have not been fully explored. In this study, the anti-inflammatory activitives and the potential mechanisms of five isosteroid alkaloids from F. Cirrhosae Bulbus were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. The pro-inflammatory mediators and cytokines were measured by Griess reagent, ELISA and qRT-PCR. The expression of MAPKs was investigated by western blotting. Treatment with the five isosteroid alkaloids in appropriate concentrations could reduce the production of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in supernatant, and suppressed the mRNA expressions of TNF-α and IL-6. Meanwhile, the five isosteroid alkaloids significantly inhibited the phosphorylated activation of mitogen activated protein kinase (MAPK) signaling pathways, including extracellular signal-regulated kinase (ERK1/2), p38 MAPK and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK). These results demonstrated that isosteroid alkaloids from F. Cirrhosae Bulbus exert anti-inflammatory effects by down-regulating the level of inflammatory mediators via mediation of MAPK phosphorylation in LPS-induced RAW264.7 macrophages, thus could be candidates for the prevention and treatment of inflammatory diseases.