Tandospirone prevents stress-induced anxiety-like behavior and visceral hypersensitivity by suppressing theta oscillation enhancement via 5-HT1A receptors in the anterior cingulate cortex in rats.

Tandospirone, a third-generation of antianxiety agent with fewer side effects, has been widely used in the treatment of anxiety. Moreover, it is interesting that tandospirone has been found to relieve gastrointestinal symptoms in patients with refractory irritable bowel syndrome who also have psychological dysfunctions. However, the underlying mechanism remains unclear. In this study, using a visceral hypersensitivity rat model induced by chronic water avoidance stress to mimic the symptoms of irritable bowel syndrome, we found that tandospirone relieved anxiety-like behavior and visceral hypersensitivity induced by stress. Meanwhile, stressed rats had increased 5-HT concentration, less 5-HT1A receptor expression, and enhanced theta oscillations in the anterior cingulate cortex (ACC). Furthermore, the power of the theta band in ACC is positively correlated with the level of visceral sensitivity. Activation of 5-HT1A receptors by its agonist, 8-OH-DPAT, to compensate for their effect in ACC reduced the enhancement of theta oscillations in ACC slices in stressed rats, whereas 5-HT1A receptor antagonist, WAY100135, facilitates theta oscillations in slices of normal rats. Tandospirone reduced the enhancement of theta band power in ACC in vitro and in vivo, thus alleviating anxiety-like behavior and visceral hypersensitivity through 5-HT1A receptors in stressed rats. These results suggest a novel mechanism by which tandospirone activates 5-HT1A receptors to relieve stress-induced anxiety and visceral hypersensitivity by suppressing theta oscillation enhancement in ACC.

Protective effects of quercetin against chronic mixed reflux esophagitis in rats by inhibiting the nuclear factor-κB p65 and interleukin-8 signaling pathways.

OBJECTIVE: To observe the effects of quercetin on chronic mixed reflux esophagitis (RE) in rats by inhibiting the nuclear factor-κB p65 (NF-κBp65) and interleukin-8 (IL-8) signaling pathways. METHODS: Forty-eight healthy male Sprague-Dawley rats were randomly divided into six groups, with 8 rats in each group: the normal intact group, the sham operation group, the RE control group, the RE group treated with omeprazole or 100 mg/kg and 200 mg/kg quercetin. The animals were sacrificed after 6 weeks of different interventions. The pathological characteristics of esophageal mucosa were observed according to the diagnostic criteria and the expressions of NF-κBp65 and IL-8 were assessed by immunohistochemistry and real-time polymerase chain reaction. RESULTS: Compared with the RE control group, esophageal mucosal injury was improved and the expressions of NF-κBp65 and IL-8 were significantly decreased in the RE group treated with omeprazole or quercetin (P < 0.05). Compared with the omeprazole group, the gross and microscopic scores of esophageal mucosal injury and the expressions of NF-κBp65 and IL-8 in the 100 mg/kg and 200 mg/kg quercetin groups were not increased (P > 0.05). There was no statistically significant difference between the RE groups treated with 100 mg/kg quercetin and 200 mg/kg quercetin. CONCLUSION: Quercetin can prevent esophageal mucosal injury in RE rats by suppressing the NF-κBp65 and IL- 8 signaling pathways.

[Mechanism of apoptosis induced by trichostatin A in leukemia Molt-4 cells analyzed by microarray].

BACKGROUND & OBJECTIVE: Histone deacetylase is overexpressed in a variety of cancers and is closely correlated with oncogenic factors. A histone-deacetylase inhibitor, trichostatin A (TSA), has been shown to induce apoptosis in many cancer cells at submicromolar concentrations. However, the mechanism remains unknown. This study was to investigate the underlying mechanism of trichostatin A on apoptosis of Molt-4 cells by characterizing the global gene expression profiles before and after TSA treatment. METHODS: PI single-labeled flow cytometry, MTT and DNA ladder were used to observe the effect of TSA on apoptosis of MOLT-4 cells and normal human peripheral blood mononuclear cells (PBMC). Microarray and reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the differentially expressed genes of Molt-4 cells after incubation with TSA. RESULTS: TSA could induce apoptosis in Molt-4 cells in a dose and time-dependent manner. Besides, the dose of TSA within the time duration which could induce significant apoptosis in Molt-4 cells did not demonstrate apparent cytotoxicity to PBMCs. After incubation with TSA for 9 hours, 313 genes were detected down-regulated by microarray. Proteins encoded by these genes included signal transduction molecules, transcription factors, enzymes etc., which were involved in the regulation of cell growth, differentiation and survival. STAT5A, MYC and ikaros were down-regulated by 80.4%, 77.3% and 83.1%, respectively. The changes of the three genes were confirmed by RT-PCR and the changes of STAT5A and MYC were further confirmed by Western blot. CONCLUSION: The inhibition of cell growth and induction of apoptosis by TSA in Molt-4 cells may be due to the changes of pro-proliferation genes and anti-apoptosis genes.