Inhibition of TNF-α/IFN-γ induced RANTES expression in HaCaT cell by naringin.

CONTEXT: Naringin is a bioflavonoid derivative and is predominantly found in Citrus paradisi Macf., Citrus sinensis (Linn.) Osbeck, Citrus unshiu Marc., Citrus reticulata Blanco cv. Nobilis, Citrus tachibana (Makino) Tanaka, Citrus junos Sieb. ex Tanaka (Rutaceae), and related citrus species. It has anti-inflammatory effects that have been well-documented, but the mechanism is poorly characterized. OBJECTIVE: The effect of naringin on production of RANTES (regulated upon activation normal T-cell expressed and secreted) in human HaCaT cells was investigated here for the first time. MATERIALS AND METHODS: The HaCaT cells were cultured in Dulbecco's modified Eagle's medium (DMEM) and the proliferation of cell was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The cells were divided into three groups including control group, tumor necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ)-stimulated group, and naringin pretreatment group (first incubated in the presence of naringin and then exposed to TNF-α/IFN-γ). The concentration of RANTES in the supernatants was determined by enzyme-linked immunosorbent assay (ELISA). The expression of RANTES mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-κB) P65 protein was detected with immunocytochemical method and western blot method. RESULTS: Naringin hardly inhibits HaCaT cells growth at concentrations rising from 0.25 to 1 mmol/L. However, RANTES expression detected in supernatant stimulated with TNF-α/IFN-γ reduced 15 and 16%, respectively, when cultured with 0.25, 0.5 mmol/L naringin. Furthermore, 1 mmol/L naringin significantly decreased RANTES mRNA level. Finally, naringin decreased the expression of NF-κB P65 protein in nuclei. DISCUSSION AND CONCLUSION: Naringin can inhibit the increased production of RANTES, which is partially via NF-κB-dependent signal pathway.

The role of adenine nucleotide and its metabolites in regulating the homeostasis of glucose and lipid metabolism / 生理学报

Glucose and lipid metabolism is the most fundamental metabolic activity of higher organisms. This process is affected by both genetic polymorphisms and environmental factors. Excessive uptake and accumulation of lipids lead to obesity and disorder of glucose metabolic homeostasis characterized by insulin resistance and hyperglycemia, suggesting that the cross-regulation between lipid and glucose metabolism happens precisely at organ, cellular and molecular levels by known mechanisms. Adenine nucleotides and their metabolites have emerged as mediators in the mutual regulation of glucose and lipid metabolism. This review summarizes the roles of purinergic signaling induced by fatty acids in glucose metabolism and the development of type 2 diabetes.

In vitro release study, in vivo evaluation of biodistribution and antitumor activity of HPMA copolymer-5-fluorouracil conjugates / 药学学报

The in vitro release behavior, in vivo biodistribution and antitumor activity of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-5-fluorouracil conjugates (P-FU) were studied. The in vitro release behavior was evaluated by determining the amount of 5-fluorouracil (5-FU) released from P-FU in mice plasma at 37 degrees C. The in vivo biodistribution and therapeutic evaluation were investigated with Kunming mice bearing hepatoma 22 (H22). The in vitro half-life (t1/2) of P-FU in mice plasma was 32.4 h. It appeared that the circulation life time of the conjugates were 166 times longer than that of 5-FU. The AUC and t1/2 of P-FU in tumor were 3.3 times and 2.3 times more than those of 5-FU, respectively. Therapeutic evaluation also demonstrated that the treatment with P-FU displayed stronger inhibition of the tumor growth when compared with that of 5-FU (P < 0.05). HPMA copolymer is a potential carrier for 5-FU for effective treatment of cancer.