Aim of the study Excessive inflammation can lead to tissue damage and dysfunction of vital organs. Hence, regulating inflammatory response is a viable therapeutic approach. In Asian countries, various inflammatory diseases have often effectively been treated with herbal remedies including the root extract of Aralia continentalis Kitagawa (Araliaceae). Here, we investigated the effect of kaurenoic acid (ent-kaur-16-en-19-oic acid: KA), a diterpenoid that is extracted from Aralia continentalis Kitagawa root, on inflammation. Results Western blot and RT-PCR analyses show that KA induced the nuclear localization of Nrf2 as low as 1 nM in concentration and that KA treatment induced the expression of Nrf2 dependent genes such as GCLC and HO-1. On the other hand, KA did not affect the degradation of cytoplasmic IκB-α, the nuclear localization of RelA (p65), and NF-κB transcriptional activity in RAW 264.7 cells treated with endotoxin. Consistent with these data, KA treatment failed to suppress gene expression of representative pro-inflammatory mediators including COX-2, nitric oxide, IL-1β, TNF-α, and IL-12, indicating that KA did not have an important impact on NF-κB activation. Conclusion Together, these results show that KA was an effective activator of Nrf2, and suggest that the beneficial effects of A. continentalis Kitagawa root extract are, at least in part, mediated by activating Nrf2.

Objectives: This study investigates the mechanism of SCE-induced apoptosis in AGS human gastric cancer cells. Materials and methods: SCE concentrations from 100 to 400 mg/ml were used. Cell viabilities were determined using MTT assay. Members of the Bcl-2 family and Bax were detected by Western blotting. RT-PCR was performed to measure the expression level of the Fas/FasL pro-apoptotic genes.Results: SCE inhibited the proliferation AGS cells for 24 or 72 h (inhibition by 3.1% ± 5.2% at 100 mg/ml and 87.3% ± 7.6% at 400 mg/ml at 24 h and by 40.2% ± 5.3% 100 mg/ml and 95.3% ± 1.3% 400 mg/ml at 72 h) and increased the sub-G1 phase (25.3% ± 5.2% at 100 mg/ml and 370.2% ± 7.2% at 400 mg/ml) and the mitochondrial membrane depolarization (11.2% ± 2.1% at 100 mg/ml and 311.5% ± 6.1% at 400 mg/ml). The SCE-induced apoptotic cell death showed the down-regulation of Bcl-2, but up-regulation of Bax. Subsequently, SCE increased the expression level of Fas/FasL, activated caspase-9 and -3, and increased reactive oxygen species generation. Also, JNK II inhibitor or a p38 MAPK inhibitor inhibited SCE-induced cell death. Discussion and conclusion: These results indicate that SCE might be an effective chemotherapeutic for the treatment of human gastric cancer.