Bee venom suppresses LPS-mediated NO/iNOS induction through inhibition of PKC-α expression

Ethnopharmacological relevance: Bee venom (BV) is a traditional Korean medicine that has been widely used with satisfactory results in the treatment of some immune-related diseases, especially rheumatoid arthritis. Aim of the study: The purpose of this study is to elucidate the molecular mechanism underlying the anti-inflammatory effects of BV, which is used in the treatment of various inflammatory diseases in traditional Korean medicine. We evaluated the anti-inflammatory effect of BV on NO generation and iNOS expression by LPS in rat C6 glioma cells. Material and methods: BV was obtained from the National Institute of Agricultural Science and Technology (NIAST) of Korea. Nitrite measurement, Immuno blot analysis, Reverse transcriptase-PCR and Electrophoretic mobility shift assay (EMSA) were used for assessment. Results: BV suppressed the LPS-induced NO generation and iNOS expression, and it also inhibited the expressions of LPS-induced pro-inflammatory molecules including Cox-2 and IL-1β in rat C6 glioma cells. Then, BV inhibited LPS-induced expression of PKC-α and MEK/ERK, not p38 and JNK. Moreover, inhibition of LPS-induced iNOS expression by BV was dependent on transcriptional activities of AP-1/NF-κB through MEK/ERK pathway. Conclusion: These results indicate that BV suppresses LPS-induced iNOS activation through regulation of PKC-α. Accordingly, BV exerts a potent suppressive effect on pro-inflammatory responses in rat C6 glioma cells. Crown