Two new sterols, 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5,22-diene (1), 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5-ene (2), were isolated together with six known compounds, ergosta-5, 24(28)-dien-3 beta, 7...Two new sterols, 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5,22-diene (1), 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5-ene (2), were isolated together with six known compounds, ergosta-5, 24(28)-dien-3 beta, 7 alpha -diol (3), ergosta-5,24(28)-dien-3 beta, 7 beta, 16 beta -triol (4), beta -amyrone (5), beta -amyrin (6), 11 alpha, 12 alpha -epoxy-14-taraxeren-3-one (7), and 6-guaiene-4 alpha, 10 alpha -diol (8) from the EtOH extract of the bark of Amoora yunnanensis (H. L. Li) C. Y. Wu. Their structures were deduced on the basis of spectral data.展开更多
Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats....Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment （intravenous injection） re- duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-a in brain tissue. Pretreatment with puerarin （intravenous injection） attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 （JAK2） and signal transducers and activators of transcription 3 （STAT3） activation and nuclear factor kappa B （NF-KB） inhibition. These observa- tions were inhibited by the alpha7 nicotinic acetylcholine receptor （a7nAchR） antagonist a-bungarotoxin （a-BGT）. In addition, puerarin pretreatment increased the expression of a7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re- sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi- ated through the activation of the cholinergic anti-inflammatory pathway.展开更多
目的:探讨散发性阿尔茨海默病(Spord ic alzhe im er d isease,SAD)患者神经型尼古丁受体α7亚单位(CHRNA7)基因多态性情况。方法:用聚合酶链式反应-温度梯度凝胶电泳(PCR-TGGE)和DNA测序技术,分析12例SAD病人CHRNA7基因全部10个外显子...目的:探讨散发性阿尔茨海默病(Spord ic alzhe im er d isease,SAD)患者神经型尼古丁受体α7亚单位(CHRNA7)基因多态性情况。方法:用聚合酶链式反应-温度梯度凝胶电泳(PCR-TGGE)和DNA测序技术,分析12例SAD病人CHRNA7基因全部10个外显子及其两侧的部分内含子基因序列。结果:在CHRNA7基因上发现1个新的突变位点,即在外显子7附近的内含子7上的117 643+GTG三碱基插入突变,未发现任何已报道的多态性位点。结论:SAD患者的CHRNA7基因多态性与其它人群可能有差异。展开更多
Berberine（BBR） is an isoquinoline alkaloid extracted from Rhizoma coptidis and has been used for treating type 2 diabetes mellitus（T2DM） in China. The development of T2 DM is often associated with insulin resistan...Berberine（BBR） is an isoquinoline alkaloid extracted from Rhizoma coptidis and has been used for treating type 2 diabetes mellitus（T2DM） in China. The development of T2 DM is often associated with insulin resistance and impaired glucose uptake in peripheral tissues. In this study, we examined whether BBR attenuated glucose uptake dysfunction through the cholinergic anti-inflammatory pathway in Hep G2 cells. Cellular glucose uptake, quantified by the 2-[N-（7-Nitrobenz-2-oxa-1,3-diazol-4-yl）-amino]-2-deoxy-D-glucose（2-NBDG）, was inhibited by 21% after Hep G2 cells were incubated with insulin（10-6 mol/L） for 36 h. Meanwhile, the expression of alpha7 nicotinic acetylcholine receptor（α7n ACh R） protein was reduced without the change of acetylcholinesterase（ACh E） activity. The level of interleukin-6（IL-6） in the culture supernatant, the ratio of phosphorylated I-kappa-B kinase-β（IKKβ） Ser181/IKKβ and the expression of nuclear factor-kappa B（NF-κB） p65 protein were also increased. However, the treatment with BBR enhanced the glucose uptake, increased the expression of α7n ACh R protein and inhibited ACh E activity. These changes were also accompanied with the decrease of the ratio of p IKKβ Ser181/IKKβ, NF-κB p65 expression and IL-6 level. Taken together, these results suggest that BBR could enhance glucose uptake, and relieve insulin resistance and inflammation in Hep G2 cells. The mechanism may be related to the cholinergic anti-inflammatory pathway and the inhibition of ACh E activity.展开更多
Aim Alpha7 nicotinic acetylcholine receptor （α7nAChR）, a subtype of nAChR regulating neurotrans- mission in central nervous system, is an essential regulator of cholinergic antiinflammatory pathway in periphery. Th...Aim Alpha7 nicotinic acetylcholine receptor （α7nAChR）, a subtype of nAChR regulating neurotrans- mission in central nervous system, is an essential regulator of cholinergic antiinflammatory pathway in periphery. The present study was to determine the effects of activation of α7nAChR on oxidant stress-induced injury in endo- thelial cells. Methods Cultured human umbilical vein endothelial cells were treated with H202 （400 μmol · L^-1） or H202plus PNU-282987 （ 10 μmol · L^-1 ）. Cell viability and membrane integrity were measured. AnnexinV ＋ PI assay, immunoblotting of bcl-2, bax and cleaved caspase-3, and immunofluorescence of apoptosis inducing factor （AIF） were performed to evaluate apoptosis. Protein expression of vascular peroxidase-1 （ VPO-1 ） and phosphor- JNK were measured by immunoblotting. Results Activation of α7nAChR by a selective agonist PNU-282987 pre-vented H202-indced decrease of cell viability and increase of lactate dehydrogenase release. Activation of α7nAChR markedly reduced cell apoptosis and intracellular oxidative stress level. Moreover, activation of α7nAChR reduced H2 02 -induced VPO-1 protein upregulation and JNK1/2 phosphorylation. The inhibitory effect of α7nAChR activa- tion on VPO-1 was blocked by JNK inhibitor SP600125. In addition, pretreatment of α7nAChR antagonist methyl- lycaconitine blocked the cytoprotective effect of PNU-282987. Conclusion These results provide the first evidence that activation of α7nAChR protects against oxidant stress-induced damage by suppressing VPO-1 in a JNK signa- ling pathway-dependent manner in endothelial cells.展开更多
Background: Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Bladder dysfunction is the common non-motor symptom of PD, most often presenting with ...Background: Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Bladder dysfunction is the common non-motor symptom of PD, most often presenting with detrusor overactivity (DO). Treatment of DO is currently limited, poorly tolerated and sometimes ineffective. Bladder responses are not only mediated by muscarinic cholinergic receptors (mAChR) but also by nicotinic cholinergic receptors (nAChR). However, nicotinic receptor subtypes and functions in the bladder are not clearly identified. Purpose: This study aimed at investigating the effect of varenicline, an alpha7 full agonist and alpha4beta2/alpha3 partial agonist, on detrusor strips in rat PD model induced by substantia nigra injection of 6-hydroxydopamine. Method: The detrusor activity was studied in an isolated organ bath system. Results: In PD group, the detrusor activity was increased, whereas varenicline decreased the DO. Conclusion: Alpha7 nAChR agonists may have therapeutic potential in treatment of bladder overactivity in PD.展开更多
Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor（α7 n ACh R） activations by a potent ag...Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor（α7 n ACh R） activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons.To further investigate the underlying mechanism,we established rat models of early-stage Huntington＇s disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water,twice a day during 4 days.Western blot assay results showed that the expression of heme oxygenase-1（HO-1）,the key component of the cholinergic anti-inflammatory pathway,in the right striatum of rat models of Huntington＇s disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water,and that the increase in HO-1 expression was independent of change in α7 n ACh R expression.These findings suggest that HO-1 expression is unrelated to α7 n ACh R density and the increase in HO-1 expression likely contributes to α7 n ACh R activation-related neuroprotective effect in early-stage Huntington＇s disease.展开更多
Alzheimer’s disease（AD）is a progressive cognitive disorder that develops predominantly in elderly patients and is characterized by cognitive impairments affecting memory,learning,and attention（Selkoe,2002）.
Two new sterols. 3 beta,7 alpha, 16 beta-trihydroxy-stigmast-5,22-diene 1,3 beta,7 alpha,16 beta-trihydroxy-stigmast-5-ene 2. were isolated together with two known ergosterols, ergosta-5,24(28)-diene-3 beta.7 alpha-di...Two new sterols. 3 beta,7 alpha, 16 beta-trihydroxy-stigmast-5,22-diene 1,3 beta,7 alpha,16 beta-trihydroxy-stigmast-5-ene 2. were isolated together with two known ergosterols, ergosta-5,24(28)-diene-3 beta.7 alpha-diol, ergosta-5,24(28)-diene-3 beta,7 beta,16 beta-triol from the bark of Amoora yunnanensis (H. L. Li) C. Y. Wu. Their structures were deduced on the basis of spectral data.展开更多
文摘Two new sterols, 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5,22-diene (1), 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5-ene (2), were isolated together with six known compounds, ergosta-5, 24(28)-dien-3 beta, 7 alpha -diol (3), ergosta-5,24(28)-dien-3 beta, 7 beta, 16 beta -triol (4), beta -amyrone (5), beta -amyrin (6), 11 alpha, 12 alpha -epoxy-14-taraxeren-3-one (7), and 6-guaiene-4 alpha, 10 alpha -diol (8) from the EtOH extract of the bark of Amoora yunnanensis (H. L. Li) C. Y. Wu. Their structures were deduced on the basis of spectral data.
基金supported by the Young Scientists Foundation of Hubei Provincial Health Department,No.QJX2012-16
文摘Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment （intravenous injection） re- duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-a in brain tissue. Pretreatment with puerarin （intravenous injection） attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 （JAK2） and signal transducers and activators of transcription 3 （STAT3） activation and nuclear factor kappa B （NF-KB） inhibition. These observa- tions were inhibited by the alpha7 nicotinic acetylcholine receptor （a7nAchR） antagonist a-bungarotoxin （a-BGT）. In addition, puerarin pretreatment increased the expression of a7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re- sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi- ated through the activation of the cholinergic anti-inflammatory pathway.
文摘目的:探讨散发性阿尔茨海默病(Spord ic alzhe im er d isease,SAD)患者神经型尼古丁受体α7亚单位(CHRNA7)基因多态性情况。方法:用聚合酶链式反应-温度梯度凝胶电泳(PCR-TGGE)和DNA测序技术,分析12例SAD病人CHRNA7基因全部10个外显子及其两侧的部分内含子基因序列。结果:在CHRNA7基因上发现1个新的突变位点,即在外显子7附近的内含子7上的117 643+GTG三碱基插入突变,未发现任何已报道的多态性位点。结论:SAD患者的CHRNA7基因多态性与其它人群可能有差异。
基金supported by the National Natural Science Foundation of China(No.81373872)
文摘Berberine（BBR） is an isoquinoline alkaloid extracted from Rhizoma coptidis and has been used for treating type 2 diabetes mellitus（T2DM） in China. The development of T2 DM is often associated with insulin resistance and impaired glucose uptake in peripheral tissues. In this study, we examined whether BBR attenuated glucose uptake dysfunction through the cholinergic anti-inflammatory pathway in Hep G2 cells. Cellular glucose uptake, quantified by the 2-[N-（7-Nitrobenz-2-oxa-1,3-diazol-4-yl）-amino]-2-deoxy-D-glucose（2-NBDG）, was inhibited by 21% after Hep G2 cells were incubated with insulin（10-6 mol/L） for 36 h. Meanwhile, the expression of alpha7 nicotinic acetylcholine receptor（α7n ACh R） protein was reduced without the change of acetylcholinesterase（ACh E） activity. The level of interleukin-6（IL-6） in the culture supernatant, the ratio of phosphorylated I-kappa-B kinase-β（IKKβ） Ser181/IKKβ and the expression of nuclear factor-kappa B（NF-κB） p65 protein were also increased. However, the treatment with BBR enhanced the glucose uptake, increased the expression of α7n ACh R protein and inhibited ACh E activity. These changes were also accompanied with the decrease of the ratio of p IKKβ Ser181/IKKβ, NF-κB p65 expression and IL-6 level. Taken together, these results suggest that BBR could enhance glucose uptake, and relieve insulin resistance and inflammation in Hep G2 cells. The mechanism may be related to the cholinergic anti-inflammatory pathway and the inhibition of ACh E activity.
文摘Aim Alpha7 nicotinic acetylcholine receptor （α7nAChR）, a subtype of nAChR regulating neurotrans- mission in central nervous system, is an essential regulator of cholinergic antiinflammatory pathway in periphery. The present study was to determine the effects of activation of α7nAChR on oxidant stress-induced injury in endo- thelial cells. Methods Cultured human umbilical vein endothelial cells were treated with H202 （400 μmol · L^-1） or H202plus PNU-282987 （ 10 μmol · L^-1 ）. Cell viability and membrane integrity were measured. AnnexinV ＋ PI assay, immunoblotting of bcl-2, bax and cleaved caspase-3, and immunofluorescence of apoptosis inducing factor （AIF） were performed to evaluate apoptosis. Protein expression of vascular peroxidase-1 （ VPO-1 ） and phosphor- JNK were measured by immunoblotting. Results Activation of α7nAChR by a selective agonist PNU-282987 pre-vented H202-indced decrease of cell viability and increase of lactate dehydrogenase release. Activation of α7nAChR markedly reduced cell apoptosis and intracellular oxidative stress level. Moreover, activation of α7nAChR reduced H2 02 -induced VPO-1 protein upregulation and JNK1/2 phosphorylation. The inhibitory effect of α7nAChR activa- tion on VPO-1 was blocked by JNK inhibitor SP600125. In addition, pretreatment of α7nAChR antagonist methyl- lycaconitine blocked the cytoprotective effect of PNU-282987. Conclusion These results provide the first evidence that activation of α7nAChR protects against oxidant stress-induced damage by suppressing VPO-1 in a JNK signa- ling pathway-dependent manner in endothelial cells.
文摘Background: Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Bladder dysfunction is the common non-motor symptom of PD, most often presenting with detrusor overactivity (DO). Treatment of DO is currently limited, poorly tolerated and sometimes ineffective. Bladder responses are not only mediated by muscarinic cholinergic receptors (mAChR) but also by nicotinic cholinergic receptors (nAChR). However, nicotinic receptor subtypes and functions in the bladder are not clearly identified. Purpose: This study aimed at investigating the effect of varenicline, an alpha7 full agonist and alpha4beta2/alpha3 partial agonist, on detrusor strips in rat PD model induced by substantia nigra injection of 6-hydroxydopamine. Method: The detrusor activity was studied in an isolated organ bath system. Results: In PD group, the detrusor activity was increased, whereas varenicline decreased the DO. Conclusion: Alpha7 nAChR agonists may have therapeutic potential in treatment of bladder overactivity in PD.
基金supported by the Région Centre-Val de Loire(2014 00094049–AP 2014-850)the European Union’s Seventh Framework Programme(FP7/2007-2013)under grant agreement n°278850(INMiND)
文摘Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor（α7 n ACh R） activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons.To further investigate the underlying mechanism,we established rat models of early-stage Huntington＇s disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water,twice a day during 4 days.Western blot assay results showed that the expression of heme oxygenase-1（HO-1）,the key component of the cholinergic anti-inflammatory pathway,in the right striatum of rat models of Huntington＇s disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water,and that the increase in HO-1 expression was independent of change in α7 n ACh R expression.These findings suggest that HO-1 expression is unrelated to α7 n ACh R density and the increase in HO-1 expression likely contributes to α7 n ACh R activation-related neuroprotective effect in early-stage Huntington＇s disease.
基金supported by a grant KAKENHI 15K06786the Center of Innovation Science and Technology based Radical Innovation and Entrepreneurship Program(COI STREAM)of the Ministry of Education,Culture,Sports,Science and Technology(MEXT),Japan
文摘Alzheimer’s disease（AD）is a progressive cognitive disorder that develops predominantly in elderly patients and is characterized by cognitive impairments affecting memory,learning,and attention（Selkoe,2002）.
文摘Two new sterols. 3 beta,7 alpha, 16 beta-trihydroxy-stigmast-5,22-diene 1,3 beta,7 alpha,16 beta-trihydroxy-stigmast-5-ene 2. were isolated together with two known ergosterols, ergosta-5,24(28)-diene-3 beta.7 alpha-diol, ergosta-5,24(28)-diene-3 beta,7 beta,16 beta-triol from the bark of Amoora yunnanensis (H. L. Li) C. Y. Wu. Their structures were deduced on the basis of spectral data.
