Astragaloside IV ameliorates insulin induced insulin resistance in HepG2 cells through reactive oxygen species mediated c-Jun N-terminal kinase pathway.

OBJECTIVE: To investigate the effects and elucidate the mechanism of Astragaloside IV (AS-IV) for insulin resistance (IR) and type 2 diabet es mellitus (T2DM). METHODS: CCK8 kit was used to detect cell viability, glucose detection kit was used to detect the concentration of glucose in cell supernatant, reactive oxygen species (ROS) detection kit and Western blot were used to explore the mechanism of Astragaloside IV (AS-IV) in improving IR. A diabetic rat model was also established by feeding high sugar and fat diet and streptozotocin (STZ) injection. After treatment with AS-IV, rosiglitazone (ROZ), or normal saline, the fasting blood glucose (FBG), C peptide (C-P), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and the glucose tolerance were assessed. RESULTS: AS-IV could effectively reduce the content of ROS and increase the glucose uptake in high insulin-treated IR-type HepG2 cells. The results of molecular mechanisms indicated that AS-IV could improve insulin resistance by reducing JNK phosphorylation and regulating c-Jun N-terminal kinase (JNK) downstream protein expression. Additionally, AS-IV could significantly reduce the levels of FBG, TNF-α, IL-6 and the glucose tolerance in diabetic rats ( < 0.05 or < 0.01). The high and medium dose groups of AS-IV could significantly increase the C-P levels in diabetic rats ( < 0.05 or < 0.01). CONCLUSIONS: Our results indicated that AS-IV improve liver IR through the JNK pathway and ROS, which meant a new molecular target for the treatment of diabetes. The AS-IV also helped to prevent and improved the insulin resistance of rats.

The levels of CD4+CD25+ regulatory T cells in patients with allergic rhinitis.

BACKGROUND: The involvement of CD4+CD25+ regulatory T cells (CD4+CD25+ TRegs) in allergic diseases was reported previously. However, it remains unclear whether CD4+CD25+ TRegs are involved in allergic rhinitis (AR). METHODS: Fresh whole blood from 20 patients with AR and 16 healthy donors was used to investigate the frequency of CD4+CD25+ and CD4+CD25hi Treg cells using flow cytometry. In addition, serum total IgE (IU/mL) levels were determined using enzyme-linked immunosorbent assays. RESULTS: Patients with AR had fewer CD4+CD25+ Treg cells (2.80 ± 1.36% vs. 3.94 ± 0.97%, P < 0.01) and CD4+CD25hi TRegs (1.53 ± 0·62% vs. 2.00 ± 0.52%, P < 0.05) than control subjects. The number of CD4+CD25+ and CD4+CD25hi TRegs was correlated negatively with total immunoglobulin E levels (r = -0.79, P < 0.01 and r = -0.61, P < 0.01, respectively). CONCLUSION: Deficient regulatory T cells might play a role in the development of AR.

Down-regulation of endogenous hydrogen sulphide pathway in nasal mucosa of allergic rhinitis in guinea pigs.

BACKGROUND: The present study was designed to explore the possible changes in endogenous hydrogen sulphide (H(2)S), a novel gasotransmitter, on the pathogenesis of allergic rhinitis (AR). METHODS: AR guinea pig model was established by nasal ovalbumin sensitisation. Guinea pigs were divided into four groups: Saline control, AR sensitised, sodium hydrosulphide (NaHS) treated, and propargylglycine (PPG) treated group. The frequency of sneezing and nose rubbing was recorded. Leukocyte infiltration in nasal lavage fluid (NLF) and plasma H(2)S level were measured. Expression of Cystathionine-beta-synthase (CBS) and Cystathionine-gamma-lyase (CSE) mRNA as H(2)S-producing enzymes in nasal mucosa was determined by real time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). RESULTS: The frequency of sneezing and nose rubbing, and levels of leukocyte infiltration in NLF were higher than those of control (P<0.01), but plasma H(2)S in sensitised guinea pigs was lower than those of control (P<0.05). From the results of RT-PCR, it was found that the expression of CSE was higher than CBS in nasal mucosa, and in sensitised guinea pigs it was lower than that of control (P<0.05). NaHS successfully increased the level of H(2)S and alleviated the symptoms of AR accompanied by up-regulation of CSE as compared with AR group (P<0.05). PPG significantly suppressed the expression of CSE and decreased the H(2)S level, yet also aggravated the symptoms of AR. CONCLUSION: H(2)S level may be negatively correlated with the process of inflammation and positively correlated with expression of CSE in nasal mucosa. The endogenous H(2)S pathway is down-regulated in AR.

Down-regulation of endogenous hydrogen sulphide pathway in nasal mucosa of allergic rhinitis in guinea pigs

Background The present study was designed to explore the possible changes in endogenous hydrogen sulphide (H2S), a novel gasotransmitter, on the pathogenesis of allergic rhinitis (AR). Methods AR guinea pig model was established by nasal ovalbumin sensitisation. Guinea pigs were divided into four groups: Saline control, AR sensitised, sodium hydrosulphide (NaHS) treated, and propargylglycine (PPG) treated group. The frequency of sneezing and nose rubbing was recorded. Leukocyte infiltration in nasal lavage fluid (NLF) and plasma H2S level were measured. Expression of Cystathionine-â-synthase (CBS) and Cystathionine-ã-lyase (CSE) mRNA as H2S-producing enzymes in nasal mucosa was determined by real time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Results The frequency of sneezing and nose rubbing, and levels of leukocyte infiltration in NLF were higher than those of control (P<0.01), but plasma H2S in sensitised guinea pigs was lower than those of control (P<0.05). From the results of RT-PCR, it was found that the expression of CSE was higher than CBS in nasal mucosa, and in sensitised guinea pigs it was lower than that of control (P<0.05). NaHS successfully increased the level of H2S and alleviated the symptoms of AR accompanied by up-regulation of CSE as compared with AR group (P<0.05). PPG significantly suppressed the expression of CSE and decreased the H2S level, yet also aggravated the symptoms of AR. Conclusion H2S level may be negatively correlated with the process of inflammation and positively correlated with expression of CSE in nasal mucosa. The endogenous H2S pathway is down-regulated in AR (AU)