Lycorine inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in RAW264.7 cells through suppressing P38 and STATs activation and increases the survival rate of mice after LPS challenge

• Published in: International immunopharmacology 2012, Vol.12 (1), p.249-256
• Main Authors: Kang, Jingjing, Zhang, Yushun, Cao, Xiang, Fan, Jie, Li, Guilan, Wang, Qi, Diao, Ying, Zhao, Zhihui, Luo, Lan, Yin, Zhimin
• Format: Article
• Language: English
• Subjects: Amaryllidaceae; Amaryllidaceae Alkaloids - pharmacology; Amaryllidaceae Alkaloids - therapeutic use; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Cell Line; COX-2; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase 2 Inhibitors - therapeutic use; Dinoprostone - metabolism; iNOS; Interleukin-6 - metabolism; Lipopolysaccharide; Lipopolysaccharides; Lycorine; Male; Medical sciences; Mice; Mice, Inbred ICR; Mitogen-Activated Protein Kinases - metabolism; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; P38; Pharmacology. Drug treatments; Phenanthridines - pharmacology; Phenanthridines - therapeutic use; RNA, Messenger - metabolism; Shock, Septic - chemically induced; Shock, Septic - drug therapy; Shock, Septic - metabolism; STAT1 Transcription Factor - metabolism; STAT3 Transcription Factor - metabolism; STATs; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2011.11.018

As a natural alkaloid extracted from Amaryllidaceae, lycorine shows various biological effects on tumor cells. Here we show that lycorine dose-dependently inhibited the LPS-induced up-regulation of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein level in RAW264.7 cells. Besides, it also inhibited NO, PGE 2, TNF-α and IL-6 release from LPS-treated RAW264.7 cells. RT-PCR experiments showed that lycorine suppressed LPS-induced iNOS but not COX-2 gene expression. Moreover, lycorine decreased LPS-induced mortality in mice. Mechanistically, LPS-induced activation of P38 and STATs pathways was suppressed significantly by lycorine. In addition, lycorine did not interfere with the phosphorylation of ERK1/2, JNK1/2 and NF-κB pathways. In conclusion, lycorine inhibits LPS-induced production of pro-inflammatory mediators and increases the survival rate of mice after LPS challenge, suggesting that lycorine could play an anti-inflammatory role in response to LPS. ►We found that lycorine inhibited the LPS-induced up-regulation of iNOS and COX-2 protein level. ►RT-PCR experiments showed that lycorine suppressed LPS-induced iNOS but not COX-2 gene expression. ►Lycorine decreased LPS-induced mortality in mice. ►Lycorine suppressed LPS-induced activation of P38 and STATs pathways.