Berberine （BBR） has a variety of pharmacological activities. Studies have reported that BBR not only reduces heat stress-induced fever but also inhibits lower body temperatures due to cold stress. Heat stress can be...Berberine （BBR） has a variety of pharmacological activities. Studies have reported that BBR not only reduces heat stress-induced fever but also inhibits lower body temperatures due to cold stress. Heat stress can be reduced via BBR treatment, which antagonizes HSP70-TNFa to regulate the body temperature alteration. In cold stress, however, the molecular mechanism of BBR-induced inhibition of hypothermia remains unclear. Therefore, we studied whether BBR promoted uncoupling protein 1 （UCP1, a crucial protein of thermogenesis） expression and its mechanism under cold stress. Wild type mice and Ucpl-/- mice were used for the in vivo experiments, and primary brown adipocytes and brown adipocytes HIB-1B were used for the in vitro studies. The cold stress was set at 4℃. The results showed that at 4℃, the body temperature of mice was decreased. BBR effectively inhibited this hypothermia. Simultaneously, Ucpl expression in brown adipose tissue （BAT） cells was significantly increased, and BBR promoted Ucpl expression. However, in Ucpl-knockout mice, the effect of BBR on hypothermia disappeared during cold stress, indicating that the main target for BBR regulation of body temperature was Ucpl. Further studies showed that the transcriptional response element NFE2 （nuclear factor erythroid-derived 2） in the upstream of the Ucpl promoter region contributed to the positive regulatory role on Ucpl expression at lower temperature. BBR could bind to the sequence of NFE2 response element in a temperature-dependent manner. Increased affinity of BBR binding to NFE2 response element in cold stress significantly strengthened and enhanced the expression of Ucpl. This work was important for understanding the role of BBR on thermogenesis in BAT, body temperature regulation and temperature tolerance under cold conditions.展开更多
Cerebral ischemia has higher incidence and causes irreversible damage to people. As a traditional drug for anti-inflammation, berberine（BBR） has recently been reported to have protective effect against cerebral isch...Cerebral ischemia has higher incidence and causes irreversible damage to people. As a traditional drug for anti-inflammation, berberine（BBR） has recently been reported to have protective effect against cerebral ischemia. However, the mechanism has not been explored thoroughly. By employing in vivo and in vitro models for cerebral ischemia and reperfusion, we studied the mechanism of BBR against the ischemia-reperfusion. We found that BBR regulated the expression of peroxisome proliferator-activated receptor（PPARγ） in a specific way upon ischemia-reperfusion injury. BBR enhanced the PPARγ expression during cerebral ischemia-reperfusion. By inhibiting PPARγ activity uisng GW9662, a PPARγ inhibitor, we confirmed that BBR protected the mouse brain against the ischemia in a PPARγ-dependent mechanism. In addition, we found that BBR reduced the overall global methylation, declined the expressions of DNMT1（DNA methyltransferases 1） and DNMT3a（DNA methyltransferases 3a） in the ischemia-reperfusion and reduced the methylation of PPARγ promoter region. Therefore, our data suggested that PPARγ was one of major targets of BBR, and such BBR-induced PPARγ expression during cerebral ischemia and reperfusion might be correlated to the reduced methylation of PPARγ promoter.展开更多
Depression is a psychological disease with no particularly effective therapy currently available.In the present study,we aimed to examine the antidepressive activity of a pharmaceutical Chinese medicine called TaiZi(T...Depression is a psychological disease with no particularly effective therapy currently available.In the present study,we aimed to examine the antidepressive activity of a pharmaceutical Chinese medicine called TaiZi(TZ)capsule,consisting of total polysaccharides of Radix Pseudostellariae and total flavonoids of both Radix Pueraria and Herba Epimedii.A tail suspension test and forced swimming test were performed to assess the effect of TZ in vivo.A plasmid of TPH2(tryptophan hydroxylase-2)was constructed to determine the exact target of TZ in vitro.In addition,mRNA expression was detected using a real-time PCR assay,and the protein expression was investigated using a Western blotting analysis.The results showed that TZ had an anti-depression effect in mouse and rat models with increased serotonin in the brain,and in the upregulation of mRNA and protein expression of TPH2 in the brain simultaneously by inhibition of NRSF(neuron restrictive silencer factor)expression because NRSF could bind to NRSE(neuron restrictive silencer element)to repress TPH2 transcription during the depression conditions.Icariin could bind to NRSE directly and block NRSF protein toward to NRSE for TPH2 inhibition.Therefore,we concluded that TZ had potential antidepressive effects because it could ameliorat the depression-like behavior in the animals,and the underlying mechanism of the effect was involved in NRSF/NRSE-TPH2 signaling.Icariin was identified as the active component of TZ.This study provided a new perspective for the development of antidepression drugs(Chinese medicines)based on NRSF/NRSE-TPH2 signaling.展开更多
基金National Natural Science Foundation of China(Grant No.81374006,81073092 and 90713043)
文摘Berberine （BBR） has a variety of pharmacological activities. Studies have reported that BBR not only reduces heat stress-induced fever but also inhibits lower body temperatures due to cold stress. Heat stress can be reduced via BBR treatment, which antagonizes HSP70-TNFa to regulate the body temperature alteration. In cold stress, however, the molecular mechanism of BBR-induced inhibition of hypothermia remains unclear. Therefore, we studied whether BBR promoted uncoupling protein 1 （UCP1, a crucial protein of thermogenesis） expression and its mechanism under cold stress. Wild type mice and Ucpl-/- mice were used for the in vivo experiments, and primary brown adipocytes and brown adipocytes HIB-1B were used for the in vitro studies. The cold stress was set at 4℃. The results showed that at 4℃, the body temperature of mice was decreased. BBR effectively inhibited this hypothermia. Simultaneously, Ucpl expression in brown adipose tissue （BAT） cells was significantly increased, and BBR promoted Ucpl expression. However, in Ucpl-knockout mice, the effect of BBR on hypothermia disappeared during cold stress, indicating that the main target for BBR regulation of body temperature was Ucpl. Further studies showed that the transcriptional response element NFE2 （nuclear factor erythroid-derived 2） in the upstream of the Ucpl promoter region contributed to the positive regulatory role on Ucpl expression at lower temperature. BBR could bind to the sequence of NFE2 response element in a temperature-dependent manner. Increased affinity of BBR binding to NFE2 response element in cold stress significantly strengthened and enhanced the expression of Ucpl. This work was important for understanding the role of BBR on thermogenesis in BAT, body temperature regulation and temperature tolerance under cold conditions.
基金The National Natural Science Foundation of China(81374006,90713043 and 81073092)
文摘Cerebral ischemia has higher incidence and causes irreversible damage to people. As a traditional drug for anti-inflammation, berberine（BBR） has recently been reported to have protective effect against cerebral ischemia. However, the mechanism has not been explored thoroughly. By employing in vivo and in vitro models for cerebral ischemia and reperfusion, we studied the mechanism of BBR against the ischemia-reperfusion. We found that BBR regulated the expression of peroxisome proliferator-activated receptor（PPARγ） in a specific way upon ischemia-reperfusion injury. BBR enhanced the PPARγ expression during cerebral ischemia-reperfusion. By inhibiting PPARγ activity uisng GW9662, a PPARγ inhibitor, we confirmed that BBR protected the mouse brain against the ischemia in a PPARγ-dependent mechanism. In addition, we found that BBR reduced the overall global methylation, declined the expressions of DNMT1（DNA methyltransferases 1） and DNMT3a（DNA methyltransferases 3a） in the ischemia-reperfusion and reduced the methylation of PPARγ promoter region. Therefore, our data suggested that PPARγ was one of major targets of BBR, and such BBR-induced PPARγ expression during cerebral ischemia and reperfusion might be correlated to the reduced methylation of PPARγ promoter.
基金The Student Research Training(SRT)Program of Tsinghua University(Grant No.1522T0221)the National Natural Science Foundation of China(Grant No.81374006 and 81073092)。
文摘Depression is a psychological disease with no particularly effective therapy currently available.In the present study,we aimed to examine the antidepressive activity of a pharmaceutical Chinese medicine called TaiZi(TZ)capsule,consisting of total polysaccharides of Radix Pseudostellariae and total flavonoids of both Radix Pueraria and Herba Epimedii.A tail suspension test and forced swimming test were performed to assess the effect of TZ in vivo.A plasmid of TPH2(tryptophan hydroxylase-2)was constructed to determine the exact target of TZ in vitro.In addition,mRNA expression was detected using a real-time PCR assay,and the protein expression was investigated using a Western blotting analysis.The results showed that TZ had an anti-depression effect in mouse and rat models with increased serotonin in the brain,and in the upregulation of mRNA and protein expression of TPH2 in the brain simultaneously by inhibition of NRSF(neuron restrictive silencer factor)expression because NRSF could bind to NRSE(neuron restrictive silencer element)to repress TPH2 transcription during the depression conditions.Icariin could bind to NRSE directly and block NRSF protein toward to NRSE for TPH2 inhibition.Therefore,we concluded that TZ had potential antidepressive effects because it could ameliorat the depression-like behavior in the animals,and the underlying mechanism of the effect was involved in NRSF/NRSE-TPH2 signaling.Icariin was identified as the active component of TZ.This study provided a new perspective for the development of antidepression drugs(Chinese medicines)based on NRSF/NRSE-TPH2 signaling.
