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Objective To investigate the effect of sodium houttuyfonate on the expression of PI3K and AKT1 and mTOR mRNA in the lung of rats with chronic obstructive pulmonary disease(COPD),and reveal the possible mechanism of the COPD treated with sodium houttuyfonate. Methods Twenty-four male Wistar rats were randomly divided into normal control group,model control group,dexamethasone group and sodium houttuyfonate group(n=6 for each). The rat models of COPD were established by intratracheal instillation of lipopolysaccharide and smudging. The expressions of PI3K and AKT1 and mTOR mRNA were determined by real-time PCR. The morphological changes of the lung tissue was examined by histopathology. Results Compared with the normal control group,the expressions of PI3K and AKT1 were significantly in-creased and mTOR mRNA was significantly decreased in the model group(P<0.01,P<0.05). Compared with the mod-el group,the expressions of PI3K and AKT1 were significantly decreased and mTOR mRNA was significantly increased in the sodium houttuyfonate group and dexamethasone group(P<0.01,P<0.05). Compared with the dexamethasone group, the expression of mTOR mRNA was significantly increased in the sodium houttuyfonate group(P<0.05). The pathological observation indicated that there were local pulmonary consolidation and a extensive neutrophil infiltration in the alveolar cav-ity. Prominent pulmonary interstitial fibrous hyperplasia was observed in the model group. The pathological manifestations were much ameliorated than those of the model group,and only mild interstitial pneumonia and a slight fibrous hyperplasia were seen in the sodium houttuyfonate and the dexamethasone groups. Conclusions Sodium houttuyfonate reduces the in-jury of lung tissue and has protective effect on COPD rats. The mechanism is probably related to the down-regulatation of expression of PI3K and AKT1 mRNA and up-regulatation of expression of mTOR mRNA in COPD rats.
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Objective·To investigate the effects of sodium houttuyfonate (SH) on neurons in early traumatic spinal cord injury (TSCI) rats and its mechanism. Methods·Forty adult female rats were randomly divided into sham group (n=8), control group (n=8) and experimental group (n=24). The sham group only received opened laminectomy without spinal cord clamping, the spinal cords in other two groups were clamped. The experimental group was divided into low [0.06 g/(kg·d)], moderate [0.12 g/(kg·d)] and high [0.24 g/(kg·d)] dose subgroups, in which SH was administrated intragastrically 1 h after operation and next two days. The other groups were given equivalent normal saline. The best therapeutic dose of SH was screened out by the results of the BBB scores and Nissl staining. To explore the neuroprotection mechanisms of SH, 72 rats were randomly divided into sham group (n=24), model group (n=24) and SH best dose group (n=24), the postoperative interventions were as same as above. Immunofluorescence and immunohistochemistry were respectively used to detect the number of motor neurons and cleaved-caspase3 positive staining neurons, the expression of Bax, Bcl-2, NeuN and cleaved-caspase3 was detected by Western blotting. Results·The BBB scores on day 5 and day 7 after operation in low dose group were higher than those of control group (all P<0.01), but lower than those of moderate and high dose groups (all P<0.01), and the scores in the moderate and high dose groups were not different significantly. On day 7 after operation, compared with moderate and high dose groups, the dissolution of Nissl bodies in low dose group and control group increased, the number of Nissl bodies reduced, and the colour shallowed. But Nissl staining in moderate and high dose groups were similar. The optimal dose of SH was 0.12 g/(kg·d), which was judged by the results of BBB scores and Nissl staining. On day 3 and day 7 after operation, compared with control group, the number of motor neurons and the expression of NeuN and Bcl-2 in SH best dose group were increased (all P<0.01), while the number of cleaved-caspase3 positive staining neurons and the expression of Bax and cleaved-caspase3 were reduced (all P<0.01). Conclusion·SH has a certain neuroprotection on neurons in TSCI, its mechanism may be through upregulating the ratio of Bcl-2/Bax, thereby reducing the neuronal apoptosis.
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Quorum sensing of bacteria and its specific gene expression regulation have a very important role in bacterial biofilm formation. LuxS and agr are the key regulatory genes in quorum sensing of Staphylococcus epidermidis, and RNA Ⅲ is the effector molecule of agr system. In order to evaluate the effects of sodium houttuyfonate in combination with erythromycin on the transcription level of S. epidermidis, serial dilution method was used to determine the MIC of sodium houttuyfonate, erythromycin and vancomycin on S. epidermidis, and fluorescent quantitative PCR method was used to detect the transcription levels of luxS, agr/RNAⅢ in different time periods after treatment on S. epidermidis by sodium houttuyfonate in combination with erythromycin, vancomycin, and erythromycin alone. Our results showed that in treatment by 1/2MIC, 1/4MIC sodium houttuyfonate, 1/2MIC sodium houttuyfonate +1/2MIC erythromycin, 1/4MIC sodium houttuyfonate+1/4MIC erythromycin, and 1/8MIC sodium houttuyfonate+1/8MIC erythromycin for ATCC 35984, they could rapidly up-regulate the expression of luxS of S. epidermidis from the beginning as compared with negative control, with significant differences (P<0.05); furthermore, sodium houttuyfonate can still up-regulate the expression of luxS even after treatment for 6, 12 and 48 h. Sodium houttuyfonate in MIC and 1/2MIC concentration can significantly down-regulate the expression of agr (P<0.05); 1/2MIC sodium houttuyfonate+1/2MIC erythromycin, 1/4MIC sodium houttuyfonate+1/4MIC erythromycin, can also significantly down-regulate the expression of agr in 6 h, 12 h and 24 h(P<0.05). Sodium houttuyfonate in MIC, can significantly down-regulate the expression of RNA Ⅲ (P<0.05), and 1/2MIC sodium houttuyfonate+1/2MIC erythromycin can also significantly down-regulate the expression of RNAⅢ(P<0.05). Therefore, our presented results showed that sodium houttuyfonate in combination with erythromycin can rapidly up-regulate the transcription of luxS of S. epidermidis, and can down-regulate the expression of agr/RNA Ⅲ in certain concentrations, and suggested that sodium houttuyfonate in combination of erythromycin could inhibit mutual aggregation between S. epidermidis and biofilm bacteria, inhibit membrane nutrition and formation of water transport channels, prevent separation of bacterial cells in biofilm, and inhibit the formation of bacterial exotoxin of S. epidermidis.
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Objective: To investigate the mechanism of sodium houttuyfonate (SH) against Pseudomonas aeruginosa (PA) targeting quorum sensing system. Methods: The microdilution method was adopted to determine the minimal inhibitory concentration (MIC) of SH and azithromycin (AZM) for PA; The effects of SH on LasA proteases activity and pyocyanin production were detected by UV spectrophotometry; The semi-quantitative PCR and qRT-PCR were used to detect the expression changes of quorum sensing regulatory genes (lasI, rhlI, lasR, rhlR, phzM, pqsA, pslA, lasA, lasB, and toxA). Results: The MIC of P. aeruginosa for SH and AZM was 512 μg/mL and 64 μg/mL, respectively; SH could significantly inhibit the activity of LasA proteases, and pyocyanin of bacteria; The morphology of P. aeruginosa was observed by agar plates; Furthermore, semi-quantitative PCR and qRT-PCR results indicated that the expression of lasI, rhlI, lasR, lasA, pslA, and phzM was significantly impact by SH. Conclusion: The results of present study suggest that SH possesses anti-quorum sensing properties and plays a role against infection by anti-quorum sensing activity.
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Objective: To investigate the effect of sodium houttuyfonate (SH) combined with EDTA-Na2 (SH/EDTA-Na2) against biofilm bacteria, and to search for an alternative antibiotics. Methods: The microdilution method and checkboard test were adopted to determine the minimal inhibitory concentration (MIC), minimal biofilm eradication concentration (MBEC), and synergistic points of SH and EDTA-Na2 for Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), and Candida albicans (CA); Time-kill (T-K) curves of three kinds of bacteria in synergistic points were determined by dilution coating method; The morphology of PA, SA, and CA was observed by scanning electronic microscope (SEM). Results: The MIC of PA, SA, and CA for SH was 2.048, 0.064, and 0.064 mg/mL, and MBEC was 2.048, 0.256, and 0.512 mg/mL, respectively; The MIC of PA, SA, and CA for EDTA-Na2 was 3.75, 0.938, and 0.117 mg/mL, and MBEC was 15, 3.75, and 30 mg/mL, respectively; The MIC of PA, SA, and CA for SH/EDTA-Na2 was 0.256/0.938, 0.008/0.233, and 0.008/0.029 mg/mL, and MBEC was 0.512/3.722, 0.032/0.469, and 0.064/0.938 mg/mL, respectively. Combination of the two drugs could significantly inhibit the growth and eradicate the biofilm of bacteria. The number of bacteria on carriers reduced notably under SEM, with no or little biofilm on carriers, compared with the blank control group. Conclusion: EDTA-Na2 could play a synergistic role in combination with SH against pathogens, and SH could inhibit the growth and eradicate biofilm of PA, SA, and CA more powerfully in combination with EDTA-Na2.
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OBJECTIVE:To evaluate the effectiveness and safety of an aerosol inhalation of Sodium Houttuyfonate injection in accessory treatment of pneumonia.METHODS:Biomedical databases,including Medline,EMbase,The Cochrane Central Register of Controlled Trials,CBM-disk and CNKI were searched.Randomized controlled trials(RCTs) and quasi-RCTs that compare aerosol inhalation of Sodium Houttuyfonate injection with placebo or other aerosol inhalation regimens were collected.A critical quality assessment and Meta-analysis were performed for included studies.RESULTS:Six RCTs were included and all of them were carried out in China.None of the trials described the method of randomization,allocation concealment,blind,and follow-up.With Junci scales,6 trials scored C degree.Compared with the control group,aerosol inhalation of Sodium Houttuyfonate injection showed significantly higher total improvement rate.We didn't find any RCTs describing the safety of Sodium Houttuyfonate injection aerosol inhalation.CONCLUSION:Because of the low quality of RCTs on Sodium Houttuyfonate injection aerosol inhalation for pneumonia and the lack of RCTs describing the safety of Sodium Houttuyfonate injection aerosol inhalation,no reliable conclusion can be drawn from our Meta-analysis about its efficacy and safety.Well-designed RCTs are urgently needed to evaluate the value and safety of aerosol inhalation of Sodium Houttuyfonate injection in treating pneumonia.