While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amylo...While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide(Aβ)were used to treat rat pheochromocytoma cells(P12)and human neuroblastoma cells(SH-SY5Y).Cell morphological changes were observed to determine the in vitro cell damage.Cell Counting Kit(CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively.Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress(ERS)-related proteins(GRP78 and CHOP),p-IRE1α,IRE1α,ASK1,p-JNK,JNK,Bax,Bcl-2,XBP-1,and Bim.Fura 2-acetoxymethyl ester(Fura-2/AM)was used to determine the intracellular calcium(Ca^(2+))concentration.Also,an AD model was constructed by injecting Aβinto the CA1 area of the hippocampus in Sprague Dawley rats.AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days.The Morris water maze experiment was conducted to test the learning and memory of rats.Hematoxylin&Eosin(H&E)and Terminal-deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick-End Labeling(TUNEL)staining were done to determine histopathological changes in the brain.Results:Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury,decreased viability,increased apoptosis,G0/G1 phase cell cycle arrest,upregulation of GRP78,CHOP,p-IRE1α,p-JNK,Bax,XBP-1 and Bim,as well as down-regulation of Bcl-2.These results were also seen with IRE1αsilencing.While Aβsuppressed the learning and memory abilities of rats,the Bushen Yizhi Formula alleviated these effects of Aβ.Brain nerve cell injury induced by Aβcould also be treated with Bushen Yizhi Formula.Conclusion:Bushen Yizhi Formula could influence ERS through the IRE1αsignaling pathway to achieve its therapeutic effects on AD.展开更多
OBJECTIVE Bushen Yizhi formula,constructed by Prof LIAO Shi-long′research group(Guangzhou University of chinese medicine),is the combination of clinical experience and modern pharmacological research,and mainly focus...OBJECTIVE Bushen Yizhi formula,constructed by Prof LIAO Shi-long′research group(Guangzhou University of chinese medicine),is the combination of clinical experience and modern pharmacological research,and mainly focuses on the etiology and pathogenesis of AD for treating both cause and symptoms.In this research,the pharmacodynamic study protocol of Bushen Yizhi formula was designed according to the characteristics and indications function of herbs in the formula,and was conformed to preclinical pharmacological research of traditional Chinese medicine for AD,The Technical Requirements of Pharmacology and Toxicology Research in New Drug Development Enacted by State Food and Drug administration also was guiding principle.METHODS A preliminary randomized double-blind clinical trail with 141 cases of AD showed that the efficiency of Bushen Yizhi formula was 61.9%and the increased mean of MMSE was 3.17,but the specific mechanism remains unclear.This study was aimed to reveal the preventive and therapeutic effect of Bushen Yizhi formula on AD rats and its related mechanism.In this research,forebrain-injected IBO-induced AD rats(cholinergic neuron lesion),senescence accelerated mouse,scopolamineinduced learning and memory deficiency rats(mild cognitive impairment)were all established.The learning and memory ability was tested with Morris water maze.Then formation of age pigment,extent of neuronal loss,activation of astrocytes,content of NTFs and degree of oxidized stress damage were determined by morphology,mmunohistochemical and molecular biology methods.RESULTS As the application of Bushen Yizhi formula,the learning and memory ability in all three groups were significantly improved,the formation of age pigment and the content of ACH in cortex and hippocampus were reduced,the activation of astrocytes and release of inflammatory factor(TNF-αand IL-1β)were inhibited,and the antioxidases(CAT,SOD,GSH-PX)were up-regulated and MDA was down-regulated.CONCLUSION Bushen Yizhi formula can prevent and treat AD rats,which might be achieved by anti-inflammatory,antioxidant and protecting cholinergic neuron.展开更多
目的分析补肾益智方联合针灸对阿尔兹海默症(AD)患者氧化应激指标水平的干预作用。方法选取我院2013年8月-2016年7月收治的86例AD患者,随机分为两组,均为43例。治疗组采取补肾益智方联合针灸治疗,对照组仅予针灸治疗。比较两组治疗前后...目的分析补肾益智方联合针灸对阿尔兹海默症(AD)患者氧化应激指标水平的干预作用。方法选取我院2013年8月-2016年7月收治的86例AD患者,随机分为两组,均为43例。治疗组采取补肾益智方联合针灸治疗,对照组仅予针灸治疗。比较两组治疗前后简易精神量表(mini-mental state examination,MMSE)评分、日常生活能力量表(Activities of Daily Living,ADL)评分、AD行为病理评定量表(behavioral pathology in Alzheimer's disease,BEHAVE-AD)评分,并测定血清谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)、超氧化物歧化酶(Superoxide Dismutase,SOD)及丙二醛(malondialdehyde,MDA)水平变化。结果治疗后两组MMSE评分明显提高,ADL、BEHAVE-AD评分明显降低(P<0.01),但治疗组改善程度较对照组显著更优(P<0.01)。治疗后两组患者血清GSH-Px、SOD水平均明显上升,MDA水平明显下降(P<0.01),但治疗组改善幅度较对照组更明显(P<0.01);两组患者不良反应比较,差异无统计学意义(χ2=0.230,P=0.632)。结论补肾益智方联合针灸能提高AD患者机体抗氧化应激能力,显著改善认知功能、生活自理能力及精神行为症状,值得进一步深入研究。展开更多
基金supported by the National Natural Science Foundation of China[81904266,82004309].
文摘While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide(Aβ)were used to treat rat pheochromocytoma cells(P12)and human neuroblastoma cells(SH-SY5Y).Cell morphological changes were observed to determine the in vitro cell damage.Cell Counting Kit(CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively.Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress(ERS)-related proteins(GRP78 and CHOP),p-IRE1α,IRE1α,ASK1,p-JNK,JNK,Bax,Bcl-2,XBP-1,and Bim.Fura 2-acetoxymethyl ester(Fura-2/AM)was used to determine the intracellular calcium(Ca^(2+))concentration.Also,an AD model was constructed by injecting Aβinto the CA1 area of the hippocampus in Sprague Dawley rats.AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days.The Morris water maze experiment was conducted to test the learning and memory of rats.Hematoxylin&Eosin(H&E)and Terminal-deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick-End Labeling(TUNEL)staining were done to determine histopathological changes in the brain.Results:Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury,decreased viability,increased apoptosis,G0/G1 phase cell cycle arrest,upregulation of GRP78,CHOP,p-IRE1α,p-JNK,Bax,XBP-1 and Bim,as well as down-regulation of Bcl-2.These results were also seen with IRE1αsilencing.While Aβsuppressed the learning and memory abilities of rats,the Bushen Yizhi Formula alleviated these effects of Aβ.Brain nerve cell injury induced by Aβcould also be treated with Bushen Yizhi Formula.Conclusion:Bushen Yizhi Formula could influence ERS through the IRE1αsignaling pathway to achieve its therapeutic effects on AD.
基金The project supported by National Natural Science Foundation of China(81273817)Shandong Province Natural Science Foundation of China(ZR2013HL062)by Foundation of Overseas Distinguished Taishan Scholars of Shandong Province
文摘OBJECTIVE Bushen Yizhi formula,constructed by Prof LIAO Shi-long′research group(Guangzhou University of chinese medicine),is the combination of clinical experience and modern pharmacological research,and mainly focuses on the etiology and pathogenesis of AD for treating both cause and symptoms.In this research,the pharmacodynamic study protocol of Bushen Yizhi formula was designed according to the characteristics and indications function of herbs in the formula,and was conformed to preclinical pharmacological research of traditional Chinese medicine for AD,The Technical Requirements of Pharmacology and Toxicology Research in New Drug Development Enacted by State Food and Drug administration also was guiding principle.METHODS A preliminary randomized double-blind clinical trail with 141 cases of AD showed that the efficiency of Bushen Yizhi formula was 61.9%and the increased mean of MMSE was 3.17,but the specific mechanism remains unclear.This study was aimed to reveal the preventive and therapeutic effect of Bushen Yizhi formula on AD rats and its related mechanism.In this research,forebrain-injected IBO-induced AD rats(cholinergic neuron lesion),senescence accelerated mouse,scopolamineinduced learning and memory deficiency rats(mild cognitive impairment)were all established.The learning and memory ability was tested with Morris water maze.Then formation of age pigment,extent of neuronal loss,activation of astrocytes,content of NTFs and degree of oxidized stress damage were determined by morphology,mmunohistochemical and molecular biology methods.RESULTS As the application of Bushen Yizhi formula,the learning and memory ability in all three groups were significantly improved,the formation of age pigment and the content of ACH in cortex and hippocampus were reduced,the activation of astrocytes and release of inflammatory factor(TNF-αand IL-1β)were inhibited,and the antioxidases(CAT,SOD,GSH-PX)were up-regulated and MDA was down-regulated.CONCLUSION Bushen Yizhi formula can prevent and treat AD rats,which might be achieved by anti-inflammatory,antioxidant and protecting cholinergic neuron.
文摘目的分析补肾益智方联合针灸对阿尔兹海默症(AD)患者氧化应激指标水平的干预作用。方法选取我院2013年8月-2016年7月收治的86例AD患者,随机分为两组,均为43例。治疗组采取补肾益智方联合针灸治疗,对照组仅予针灸治疗。比较两组治疗前后简易精神量表(mini-mental state examination,MMSE)评分、日常生活能力量表(Activities of Daily Living,ADL)评分、AD行为病理评定量表(behavioral pathology in Alzheimer's disease,BEHAVE-AD)评分,并测定血清谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)、超氧化物歧化酶(Superoxide Dismutase,SOD)及丙二醛(malondialdehyde,MDA)水平变化。结果治疗后两组MMSE评分明显提高,ADL、BEHAVE-AD评分明显降低(P<0.01),但治疗组改善程度较对照组显著更优(P<0.01)。治疗后两组患者血清GSH-Px、SOD水平均明显上升,MDA水平明显下降(P<0.01),但治疗组改善幅度较对照组更明显(P<0.01);两组患者不良反应比较,差异无统计学意义(χ2=0.230,P=0.632)。结论补肾益智方联合针灸能提高AD患者机体抗氧化应激能力,显著改善认知功能、生活自理能力及精神行为症状,值得进一步深入研究。
