Inhibitory effects of herbal alkaloids on the tumor necrosis factor-α and nitric oxide production in lipopolysaccharide-stimulated RAW264 macrophages.
Chem Pharm Bull (Tokyo)
; 59(3): 388-91, 2011.
Article
em En
| MEDLINE
| ID: mdl-21372424
ABSTRACT
It is beneficial to treat chronic inflammatory condition in patients through diets that inhibit the production of proinflammatory cytokines and mediators such as tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Since less attention has been paid to alkaloids in the diets than to polyphenols in this regard, we aimed at investigating anti-inflammatory activity of herb-derived alkaloids through suppression of TNF-α and NO production in lipopolysaccharide (LPS)-stimulated mouse RAW264 and/or human THP-1 cells. A harmala alkaloid, harmine, an opium alkaloid, papaverine, and Lycoris alkaloids, lycorine and lycoricidinol, showed TNF-α suppressive activities stronger than or comparable to that of a reference polyphenol, butein, in RAW264 cells (IC(50)=4, 10, 2.1, 0.02, and 8 µM, respectively). Other alkaloids showed no or marginal to moderate inhibitory activities. Similar tendency of inhibition was found for NO production in RAW264 cells and TNF-α production in THP-1 cells. In addition, harmine was found to suppress interleukin-6 (IL-6) production in RAW264 cells. The above four inhibitory alkaloids had essentially no antioxidative property in the superoxide anion scavenging assay. Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) showed that harmine caused neither prevention of nuclear factor-κB (NF-κB) translocation into the nucleus nor inhibition of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation, while that the LPS-induced transcription of TNF-α and inducible NO synthase was dose-dependently attenuated by harmine. This result suggests that the molecular mechanism of harmine action is different from those of many other anti-inflammatory phytochemicals. In conclusion, some herbal alkaloids like harmine, in spite of lacking antioxidative property, have potential as anti-inflammatory agents that strongly suppress TNF-α and NO production by a unique mechanism.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Necrose Tumoral alfa
/
Alcaloides
/
Macrófagos
/
Anti-Inflamatórios
/
Óxido Nítrico
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Chem Pharm Bull (Tokyo)
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Japão