Saikosaponin a, an active compound of Radix Bupleuri, attenuates inflammation in hypertrophied 3T3-L1 adipocytes via ERK/NF-κB signaling pathways

Bupleurum falcatum L. is employed in oriental medicine in Korea. This root has been used for antiinflam-matory, anti-pyretic, and anti-hepatotoxic effects in the treatments of common cold, fever, and hepatitis. One of major bioactive compounds of Radix Bupleuri is the saikosaponin a (SSNa). However, little is known concerning the effects of SSNa on obesity associated with a state of low-grade inflammation. Consequently, this study was conducted to determine the inhibition of the inflammation pathway of SSNa in obesity. MTT assay was conducted for cytotoxicity and viability; nuclear and cytoplasmic fractions were extracted from adipocytes for translocation of nuclear factor-kappa B cells (NF-kappa B); nitric oxide (NO) production and secretion using Griess reagent; reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting for mRNA and protein levels associated with inflammation in the hypertrophied adipocytes. The results revealed that SSNa significantly decreased the expression of tumor necrosis factor-alpha (TNF alpha), interleukin (IL) -1 beta and IL-6 as proinflammatory cytokines, compared to that of non-treated control cells. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as inflammatory factors were reduced by treatment of these cells with SSNa and also suppressed NO production. Phosphorylation of I kappa B alpha was inhibited and translocation of NF-kappa B was suppressed via the ERK pathway in response to SSNa treatment. In conclusion, the results demonstrated that SSNa can inhibit the expression of inflammatory-associatied genes in hypertrophied 3T3-L1 adipocytes and is a potent inhibitor of NF-kappa B activation. Thus these results suggest that SSNa is a novel therapeutic agent against that can be used against obesity-associated inflammation.