期刊
ANTIOXIDANTS
卷 10, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/antiox10091430
关键词
Ergosta-7,9(11),22-trien-3 beta-ol (EK100); Cordyceps militaris; anti-inflammatory response; MAPK/AP-1 signaling pathways; IL-6/JAK/STAT signaling pathways; Nrf2/ HO-1 signaling pathway; atomic force microscopy (AFM)
资金
- Chinese Medicine Research Center, China Medical University
- Ministry of Education (MOE) in Taiwan [CMRC-CHM-4]
- China Medical University [CMU107-ASIA-24, CMU103-ASIA-21]
The study demonstrated that EK100 exhibited anti-inflammatory properties by activating antioxidative Nrf2/HO-1 signaling and inhibiting TLR4-related MAPK/AP-1 induced IL-6/JAK/STAT pathways in LPS-stimulated cells in vitro.
Chronic inflammation induces autoimmune disorders and chronic diseases. Several natural products activate nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, attenuating inflammatory responses. Ergosta-7,9(11),22-trien-3 beta-ol (EK100) isolated from Cordyceps militaris showed antiinflammatory and antioxidative activity, but those mechanisms are still unclear. This study is the first to investigate EK100 on antioxidant Nrf2 relative genes expression in LPS-stimulated macrophage-like cell lines. The results showed that EK100 reduced IL-6 (interleukin-6) and tumor necrosis factor-alpha production. EK100 also attenuated a mitogen-activated protein kinase/activator protein-1 (MAPK/AP-1) pathway and interleukin-6/Janus kinase/signal transducer and activator of transcription (IL-6/JAK/STAT) pathway in LPS-stimulated cells. Toll-like receptor 4 (TLR4) inhibitor CLI-095 and MAPK inhibitors can synergize the anti-inflammatory response of EK100 in LPS-stimulated cells. Moreover, EK100 activated Nrf2/HO-1 (heme oxygenase-1) signaling in LPS-stimulated murine macrophage-like RAW264.7 cells, murine microglial BV2 cells, and human monocytic leukemia THP-1 cells. However, Nrf2 small interfering RNA (Nrf2 siRNA) reversed EK100-induced antioxidative proteins expressions. In conclusion, EK100 showed anti-inflammatory responses via activating the antioxidative Nrf2/HO-1 signaling and inhibiting TLR4 relatedMAPK/AP-1 induced IL-6/JAK/STAT pathways in the LPS-stimulated cells in vitro. The results suggest EK100 acts as a novel antioxidant with multiple therapeutic targets that can potentially be developed to treat chronic inflammation-related diseases.
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