Suppression of tumour necrosis factor-alpha by Schizonepeta tenuifolia water extract via inhibition of IkappaBalpha degradation and Jun N-terminal kinase/stress-activated protein kinase activation.

OBJECTIVES: The anti-inflammatory effects of an aqueous extract of Schizonepeta tenuifolia on lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in vivo and in vitro have been investigated.
METHODS: C57BL/6 mice were orally administered phosphate-buffered saline (control) or S. tenuifolia water extract (50, 200, 500 or 1000 mg/kg) for 10 days before intraperitoneal administration of LPS (1.3 mg/kg). Blood samples were obtained 1 h after LPS challenge, followed by determination of TNF-alpha and IL-6 levels. Peritoneal macrophages from thioglycollate-injected mice were obtained and stimulated with LPS and S. tenuifolia water extract for viability assay, cytokine analysis, real-time RT PCR and Western blotting. KEY
FINDINGS: Oral administration of S. tenuifolia water extract to mice significantly reduced LPS-induced serum levels of TNF-alpha, but not IL-6. When peritoneal macrophages were treated in vitro with S. tenuifolia water extract, the inhibition of LPS-induced TNF-alpha was more pronounced than that of IL-6 at the level of secreted protein and mRNA. S. tenuifolia water extract reduced the degradation of IkappaBalpha and the nuclear relocation of p65 NF-kappaB, but the phosphorylation of IkappaBalpha was not affected. Inhibition of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) by S. tenuifolia water extract led secondarily to the inhibition of phospho-c-Jun and phospho-ATF-2.
CONCLUSIONS: These results indicated that the downregulation of TNF-alpha by S. tenuifolia water extract may have involved the inhibition of both IkappaBalpha degradation and activation of c-Jun and ATF-2 involving suppression of JNK/SAPK.