RESUMO
Salidroside (SAL), a major bioactive compound of Rhodiola crenulata, has significant anti-hypoxia effect, however, its underlying molecular mechanism has not been elucidated. In order to explore the protective mechanism of SAL, the lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide dismutase (SOD) and hypoxia-induced factor 1α (HIF-1α) were measured to establish the PC12 cell hypoxic model. Cell staining and cell viability analyses were performed to evaluate the protective effects of SAL. The metabolomics and bioinformatics methods were used to explore the protective effects of salidroside under hypoxia condition. The metabolite-protein interaction networks were further established and the protein expression level was examined by Western blotting. The results showed that 59 endogenous metabolites changed and the expression of the hub proteins of CK2, p-PTEN/PTEN, PI3K, p-Akt/Akt, NF-κB p65 and Bcl-2 were increased, suggesting that SAL could increase the expression of CK2, which induced the phosphorylation and inactivation of PTEN, reduced the inhibitory effect on PI3K signaling pathways and activated the PI3K/Akt/NF-κB survival signaling pathway. Our study provided an important insight to reveal the protective molecular mechanism of SAL as a novel drug candidate.
RESUMO
OBJECTIVE: To clarify the effect of total glucosides from paeony(PTG) on irritable bowel syndrome (IBS), and to explore the molecular mechanism of PTG on alleviating diarrhea symptoms and abdominal pain.METHODS: The diarrhea model was conducted by exposing rat to restraint stress stimulation and bellyache model was conducted by subcutaneous injection of neostigmine to mice. Based on these two models, the curative effect of PTG on IBS was investigated. To investigate the regulative effects of PTG on Caco-2 cells, the Caco-2 monolayer cell model with barrier dysfunction was established by trypsin stimulation, and the inflammatory Caco-2 cell model was established by interleukin-1β (IL-1β) stimulation.RESULTS: PTG could significantly reduce the frequency of defecation in diarrhea rat model (P<0.05) and relieve abnormal bowel movements in bellyache mice model (P<0.05). After PTG treatment, the TEER value of Caco-2 monolayer was significantly increased (P<0.01), the transmittance of fluorescence yellow was significantly decreased (P<0.001) and the expression of tight junction (ZO-1)protein was notably up-regulated (P<0.001). In addition, the gene and protein expression of nuclear factor profilin kappa B(IκBα)in inflammatory Caco-2 cell model was significantly improved (P<0.001) after PTG treatment.CONCLUSION: PTG significantly ameliorates IBS symptoms by protecting the barrier function of Caco-2 cell monolayer and relieving inflammation of Caco-2 cells.
RESUMO
Objectives To investigate the effect of paeoniflorin(PF)in ameliorating the irritable bowel syndrome(IBS)such as diarrhea and bellyache,and the barrier function of PF on intestinal epithelial cell and inflammation.Methods The diarrhea model was conducted by exposing rat to restraint stress stimulation and bellyache model was conducted by subcutaneous injection of neostig?mine to mice.The Caco-2 monolayer cell model with barrier dysfunction was established by trypsin stimulation and the inflammatory Caco-2 cell model was established by interleukin-1β(IL-1β)stimulation.On the basis of these models,effects of PF at different doses (low 14 mg/kg·d,medium 28 mg/kg·d,and high 56 mg/kg·d)on IBS syndromes and Caco-2 cell function were investigated. Re-sults PF could significantly reduce the frequency of defecation in diarrhea rat model(P<0.05)and relieve abnormal bowel move?ments in bellyache mice model(P<0.05).PF significantly increased TEER value(P<0.01),decreased the transmittance of fluores?cein(P<0.01)and up-regulated the expression of tight junction(ZO-1)protein(P<0.01).The gene and protein expression of nucle?ar factor profilin kappa Bα(IκBα)in inflammatory Caco-2 cell model was significantly improved(P<0.01)when treated with PF. Conclusion Our study proves for the first time that PF significantly ameliorated the diarrhea and bellyache symptoms of IBS in the di?arrhea model and bellyache model.The PF intervention effect on ZO-1 and IκBα protein might be one of the molecular mechanism of ameliorating the symptoms of IBS.
RESUMO
<p><b>OBJECTIVE</b>To examine the abilities of theanine and houpu extracts (HE) to reverse behavioral indexes (separation vocalization, stress-induced analgesia and activity).</p><p><b>METHOD</b>7-day-old chicks received IP injection of theanine and HE 30 min before being tested in the presence of three social companions or in isolation for 3-min observation period. Dependent measures were: a) Chicks were placed into an infrared ray device to calculate their spontaneous activities by a computer program b) record the separation vocalizations for every chick. c) In the experiment of stress-induced analgesia, 50 uL of formalin (0.1%) was injected into the plantar of the animal foot to index stress-induced analgesia (i. e. foot-lift frequency, foot-lift duration and peck frequency).</p><p><b>RESULT</b>In the experiments, isolated chicks exhibited more vocalizations (P < 0.01) and fewer pain-related behaviors than non-isolated chicks (P < 0.01). Theanine (12.5, 25, 50 mg x kg(-1)) and HE (25 mg x kg(-1)) decrease separately the tendency (dB) of the principal frequency (P < 0.05, P < 0.01); The stress induced analgesia can be reversed by theanine in 25, 50 mg x kg(-1). Both of the materials do not affect the spontaneous activities in this chick model without causing sedation.</p><p><b>CONCLUSION</b>These results suggest that theanine and HE in the dosages may be useful in modulating anxiety states. They are seems no synergism in the chick model.</p>