No abstract

Quercetin, apigenin, and luteolin inhibited cytotoxicity in RIN cells and attenuated the decrease of glucose-stimulated insulin secretion in islets by IL-1beta and IFN-gamma.

No abstract

Cytokines produced by immune cells infiltrating pancreatic islets are important mediators of ß-cell destruction in insulin-dependent diabetes mellitus. Cytokines stimulate an inducible form of nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, leading to insulin insufficiency. In the present study, the effects of Artemisia capillaris extract (ACE) on cytokine-induced ß-cell damage were examined. Treatment of RINm5F (RIN) rat insulinoma cells with interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ) induced cell damage. ACE completely protected IL-1ß and IFN-γ-mediated cytotoxicity in a concentration-dependent manner. Incubation with ACE resulted in a significant reduction in IL-1ß and IFN-γ-induced NO production, a finding that correlated well with reduced levels of the iNOS mRNA and protein. The molecular mechanism by which ACE inhibited iNOS gene expression appeared to involve the inhibition of NF-κB activation. The IL-1ß and IFN-γstimulated RIN cells showed increases in NF-κB binding activity and p65 subunit levels in the nucleus, and IκB• degradation in cytosol compared to unstimulated cells. Furthermore, ACE restored the cytokine-induced inhibition of insulin release from isolated islets. These results suggest that ACE protects ß-cells by suppressing NF-κB activation.

Abstract. Scutellaria barbata has been used to treat cancer in Chinese medicine. The responsible anticancer mechanism, however, is not clear. Here we demonstrated an inhibitory mechanism due to a Scutellaria barbata extract (SBE) on a human promyelocytic leukemia cell line (HL-60) that has a mutation in the tumor suppressor gene p53. HL-60 cells were incubated with various concentrations of SBE. After a 24-h incubation, cytotoxicity and apoptosis were determined by MTT and DNA fragmentation assay, respectively. After treatment with SBE, cell cycle arrest was determined by measuring the cell number stained by 5'-bromo-2'-deoxyuridine (BrdU) and 7-amino-actinomycin D (7-AAD). Treatment of cells with SBE resulted in a concentration-and timedependent inhibition of growth and a G 1 phase arrest of the cell cycle. This effect was associated with a marked decrease in the protein expression of cyclin A, D1, D2, D3, and E and their activating partners, cyclin-dependent kinases (CDK) 2, 4, and 6 with concomitant upregulation of p21, cyclindependent kinase inhibitor. Downstream of the CDK inhibitory protein-CDK/cyclin cascade, SBE decreased phosphorylation level of retinoblastoma protein. SBE treatment also resulted in apoptosis evidenced by an increase of sub-G 1 phase cells, DNA fragmentation and degradation of the inhibitory protein for the caspase-activated deoxyribonuclease. The molecular mechanism during SBE-mediated growth inhibition in HL-60 cells may be due to modulation of the cell-cycle machinery and the induction of apoptosis.