黄芩抗阿尔茨海默病研究概况
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摘要
阿尔茨海默病(Alzheimer's disease)是一种以认知功能障碍为主要病症的神经退行性疾病,病理特征以老年斑(senile plaques,SP)的形成、神经纤维缠结(neurofibrillary tangles,NFT)和神经元的丢失为主,其发病机制复杂,且目前尚无有效治疗手段。黄芩活性成分以黄酮类化合物为主,除具有广泛的如抗炎、抗氧化、抗肿瘤和免疫调节等多种药理作用外,还可以用于神经系统疾病,因而被纳入抗阿尔茨海默病研究。研究表明黄芩有效活性成分可对抗阿尔茨海默病相关炎症、氧化应激、神经毒性并保护神经元,从而改善阿尔茨海默病模型动物病况,逆转其行为认知功能,为阿尔茨海默病的治疗提供新思路。本文就阿尔茨海默病相关发病机制,阐述黄芩抗阿尔茨海默病作用机制。
Alzheimer's disease( AD) is a neurodegenerative disease with cognitive dysfunction. The main pathological features of the disease are the SP,the NFT and the loss of neurons.The mechanism of the disease is complex,and there is no effective treatment.The main active ingredient of Scutellaria baicalensis Georgi is flavonoids,which has good effect on inflammation,oxidation,tumor and immune regulation,and it can be used as an anti-AD drug.Many study show that the active ingredient of Scutellaria baicalensis Georgi can resist AD related inflammation,oxidative stress,neurotoxicity and protect the neurons,thus improving the pathological condition of AD model,reversing their cognitive dysfunction,and providing new idea for the treatment of AD.In this paper,the mechanism of Scutellaria baicalensis Georgi resisting AD was discussed on the pathogenesis of AD.
Alzheimer's disease( AD) is a neurodegenerative disease with cognitive dysfunction. The main pathological features of the disease are the SP,the NFT and the loss of neurons.The mechanism of the disease is complex,and there is no effective treatment.The main active ingredient of Scutellaria baicalensis Georgi is flavonoids,which has good effect on inflammation,oxidation,tumor and immune regulation,and it can be used as an anti-AD drug.Many study show that the active ingredient of Scutellaria baicalensis Georgi can resist AD related inflammation,oxidative stress,neurotoxicity and protect the neurons,thus improving the pathological condition of AD model,reversing their cognitive dysfunction,and providing new idea for the treatment of AD.In this paper,the mechanism of Scutellaria baicalensis Georgi resisting AD was discussed on the pathogenesis of AD.
引文
[1]MCDADE E,BATEMAN R J.Stop Alzheimer's before it starts[J].Nature,2017,547(7662):153.
[2]陈阳,郑柳明,韦英海.中医药治疗老年痴呆研究进展[J].当代医学,2015,21(7):8-9.
[3]王丛笑,宋军营,张振强.VEGF在阿尔茨海默病中相关作用机制的研究[J].中医学报,2015,30(1):109-113.
[4]徐丹洋,陈佩东,张丽,等.黄芩的化学成分研究[J].中国实验方剂学杂志,2011,17(1):78-80.
[5]钟金宝,王丽丽.黄芩的现代药理活性及安全性研究[J].九江学院学报(自然科学版),2015,30(1):67-71.
[6]张琳琳,宋宛珊,王凯,等.阿尔茨海默病发病机制及药物治疗研究进展[J].世界中医药,2017,12(5):1200-1203.
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[8]ARMSTRONG R A.The pathogenesis of Alzheimer's disease:a reevaluation of the"amyloid cascade hypothesis"[J].Int J Alzheimers Dis,2011,2011(2011):630865.
[9]陶长秀,杨文明,汪美霞,等.阿尔茨海默病发病机制研究概览[J].中医药临床杂志,2015,27(10):1370-1372.
[10]艾伟鹏,谢利霞,刘宏乐,等.黄芩素对β-淀粉样蛋白纤维化及其细胞毒性的影响[J].医药导报,2013,32(3):303-306.
[11]ZHU Y,WANG J.Wogonin increasesβ-amyloid clearance and inhibits tau phosphorylation via inhibition of mammalian target of rapamycin:potential drug to treat Alzheimer's disease[J].Neurological Sciences,2015,36(7):1181-1188.
[12]赵宇红,黄韧,徐杰,等.芹黄素对Aβ25-35诱导损伤的海马神经元的保护作用[J].中国药理学通报,2005,21(8):996-998.
[13]王玲,朱鸣峰.阿尔茨海默病发病机制的研究进展[J].吉林医学,2013,34(3):531-532.
[14]李振华,承欧梅,蒋青松,等.黄芩苷抑制beta淀粉样蛋白诱导的海马COX-2蛋白表达[J].中国中西医结合杂志,2011,31(5):676-679.
[15]CHONG C,LI X,GAO P,et al.Baicalin attenuates Alzheimer-like pathological changes and memory deficits induced by amyloidβ1–42,protein[J].Metabolic Brain Disease,2015,30(2):537-544.
[16]PIAO H Z,JIN S A,CHUN H S,et al.Neuroprotective effect of wogonin:potential roles of inflammatory cytokines[J].Arch Pharm Res,2004,27(9):930-936.
[17]YEH C H,SHIH H C,HONG H M,et al.Protective effect of wogonin on proinflammatory cytokine generation via Jak1/3-STAT1/3 pathway in lipopolysaccharide stimulated BV2 microglial cells[J].Toxicol Ind Health,2015,31(10):960-966.
[18]TANG W,SUN X,FANG J S,et al.Flavonoids from Radix Scutellariae as potential stroke therapeutic agents by targeting the second postsynaptic density 95(PSD-95)/disc large/zonula occludens-1(PDZ)domain of PSD-95[J].Phytomedicine,2004,11(4):277-284.
[19]杨欢,杨滢霖,程笑,等.黄芩提取物对脂多糖诱导BV2细胞炎症反应作用及机制探讨[J].中国药学杂志,2018,53(4):268-272.
[20]李明,陈伟强,李岩,等.黄芩苷对脂多糖诱导的巨噬细胞NF-κB活化和炎症因子表达的影响[J].现代生物医学进展,2009,9(22):4219-4221,4278.
[21]PATIL C S,SINGH V P,Satyanarayan P S,et al.Protective effect of flavonoids against aging-and lipopolysaccharide-induced cognitive impairment in mice[J].Pharmacology,2003,69(2):59-67.
[22]HA S K,MOON E,KIM S Y.Chrysin suppresses LPSstimulated proinflammatory responses by blocking NF-κB and JNK activations in microglia cells[J].Neurosci Lett,2010,485(3):143-147.
[23]CARMELIET P,JAIN R K.Angiogenesis in cancer and other diseases[J].Nature,2000,407(6801):249.
[24]CHENG R,LI C,LI C,et al.The artemisinin derivative artesunate inhibits corneal neovascularization by inducing ROS-dependent apoptosis in vascular endothelial cells[J].Invest Ophthalmol Vis Sci,2013,54(5):3400-3409.
[25]DING H,WANG H,ZHAO Y,et al.Protective Effects of Baicalin on Aβ1-42-Induced Learning and Memory Deficit,Oxidative Stress,and Apoptosis in Rat[J].Cell Mol Neurobiol,2015,35(5):623-632.
[26]GAO Z,HUANG K,XU H.Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells[J].Pharmacological Research,2001,43(2):173-178.
[27]王雅芳,李婷,唐正海,等.中药黄芩的化学成分及药理研究进展[J].中华中医药学刊,2015,33(1):206-211.
[28]辛文妤,宋俊科,何国荣,等.黄芩素和黄芩苷的药理作用及机制研究进展[J].中国新药杂志,2013,22(6):647-653.
[29]VENIGALLA M,GYENGESI E,SHARMAN M J,et al.Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease[J].Neurochem Int,2015,95(8):63-74.
[30]ANDORN A C,BRITTON R S,BACON B R,et al.Ascorbate-stimulated lipid peroxidation and non-heme iron concentrations in Alzheimer disease[J].Mol Chem Neuropathol,1998,33(1):15-26.
[31]SUGIHARA N,ARAKAWA T,OHNISHI M,et al.Antiand pro-oxidative effects of flavonoids on metal-induced lipid hydroperoxide-dependent lipid peroxidation in cultured hepatocytes loaded with alpha-linolenic acid[J].Free Radical Biol Med,1999,27(11-12):1313.
[32]SOUZA L C,ANTUNES M S,FILHO C B,et al.Flavonoid Chrysin prevents age-related cognitive decline via attenuation of oxidative stress and modulation of BDNF levels in aged mouse brain[J].Pharmacol Biochem Be,2015(134):22-30.
[33]MORITA A,SOGA K,NAKAYAMA H,et al.Neuronal differentiation of human IPS cells induced by baicalin via regulation of b HLH gene expression[J].Biochem Bioph Res Co,2015,465(3):458-463.
[34]VENIGALLA M,GYENGESI E,SHARMAN M J,et al.Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease[J].Neurochem Int,2015,95(8):63-74.
[35]JEON S J,RHEE S Y,SEO J E,et al.Oroxylin A increases BDNF production by activation of MAPK-CREB pathway in rat primary cortical neuronal culture[J].Neurosci Res,2011,69(3):214.
[36]JEON S J,BAK H,SEO J,et al.Oroxylin A Induces BDNF Expression on Cortical Neurons through Adenosine A2A Receptor Stimulation:A Possible Role in Neuroprotection[J].Biomol Ther,2012,20(1):27.
[37]刘树玲,刘梅芳,朱宝亮.中草药活性成分治疗阿尔茨海默病的研究进展[J].医学综述,2010,16(18):107-109.
[38]赵宇红,李芳芳,曾宇.芹黄素对SAMP8小鼠学习记忆及突触可塑性的影响[J].中国老年学杂志,2015,35(15):4113-4116.
[39]CHO J,LEE H K.Wogonin inhibits excitotoxic and oxidative neuronal damage in primary cultured rat cortical cells[J].Eur J Pharmacol,2004,485(1-3):105-110.
[40]LOSI G,PUIA G,GARZON G,et al.Apigenin modulates GABAergic and glutamatergic transmission in cultured cortical neurons[J].Eur J Pharmacol,2004,502(1-2):41-46.
[41]GRESAARRIBAS N,SERRATOSA J,SAURA J,et al.Inhibition of CCAAT/enhancer binding proteinδexpression by chrysin in microglial cells Results in anti-inflammatory and neuroprotective effects[J].J Neurochem,2010,115(2):526-536.
[2]陈阳,郑柳明,韦英海.中医药治疗老年痴呆研究进展[J].当代医学,2015,21(7):8-9.
[3]王丛笑,宋军营,张振强.VEGF在阿尔茨海默病中相关作用机制的研究[J].中医学报,2015,30(1):109-113.
[4]徐丹洋,陈佩东,张丽,等.黄芩的化学成分研究[J].中国实验方剂学杂志,2011,17(1):78-80.
[5]钟金宝,王丽丽.黄芩的现代药理活性及安全性研究[J].九江学院学报(自然科学版),2015,30(1):67-71.
[6]张琳琳,宋宛珊,王凯,等.阿尔茨海默病发病机制及药物治疗研究进展[J].世界中医药,2017,12(5):1200-1203.
[7]QUERFURTH H W,LAFERLA F M.Alzheimer's disease[J].New Engl J Med,2010,362(4):329.
[8]ARMSTRONG R A.The pathogenesis of Alzheimer's disease:a reevaluation of the"amyloid cascade hypothesis"[J].Int J Alzheimers Dis,2011,2011(2011):630865.
[9]陶长秀,杨文明,汪美霞,等.阿尔茨海默病发病机制研究概览[J].中医药临床杂志,2015,27(10):1370-1372.
[10]艾伟鹏,谢利霞,刘宏乐,等.黄芩素对β-淀粉样蛋白纤维化及其细胞毒性的影响[J].医药导报,2013,32(3):303-306.
[11]ZHU Y,WANG J.Wogonin increasesβ-amyloid clearance and inhibits tau phosphorylation via inhibition of mammalian target of rapamycin:potential drug to treat Alzheimer's disease[J].Neurological Sciences,2015,36(7):1181-1188.
[12]赵宇红,黄韧,徐杰,等.芹黄素对Aβ25-35诱导损伤的海马神经元的保护作用[J].中国药理学通报,2005,21(8):996-998.
[13]王玲,朱鸣峰.阿尔茨海默病发病机制的研究进展[J].吉林医学,2013,34(3):531-532.
[14]李振华,承欧梅,蒋青松,等.黄芩苷抑制beta淀粉样蛋白诱导的海马COX-2蛋白表达[J].中国中西医结合杂志,2011,31(5):676-679.
[15]CHONG C,LI X,GAO P,et al.Baicalin attenuates Alzheimer-like pathological changes and memory deficits induced by amyloidβ1–42,protein[J].Metabolic Brain Disease,2015,30(2):537-544.
[16]PIAO H Z,JIN S A,CHUN H S,et al.Neuroprotective effect of wogonin:potential roles of inflammatory cytokines[J].Arch Pharm Res,2004,27(9):930-936.
[17]YEH C H,SHIH H C,HONG H M,et al.Protective effect of wogonin on proinflammatory cytokine generation via Jak1/3-STAT1/3 pathway in lipopolysaccharide stimulated BV2 microglial cells[J].Toxicol Ind Health,2015,31(10):960-966.
[18]TANG W,SUN X,FANG J S,et al.Flavonoids from Radix Scutellariae as potential stroke therapeutic agents by targeting the second postsynaptic density 95(PSD-95)/disc large/zonula occludens-1(PDZ)domain of PSD-95[J].Phytomedicine,2004,11(4):277-284.
[19]杨欢,杨滢霖,程笑,等.黄芩提取物对脂多糖诱导BV2细胞炎症反应作用及机制探讨[J].中国药学杂志,2018,53(4):268-272.
[20]李明,陈伟强,李岩,等.黄芩苷对脂多糖诱导的巨噬细胞NF-κB活化和炎症因子表达的影响[J].现代生物医学进展,2009,9(22):4219-4221,4278.
[21]PATIL C S,SINGH V P,Satyanarayan P S,et al.Protective effect of flavonoids against aging-and lipopolysaccharide-induced cognitive impairment in mice[J].Pharmacology,2003,69(2):59-67.
[22]HA S K,MOON E,KIM S Y.Chrysin suppresses LPSstimulated proinflammatory responses by blocking NF-κB and JNK activations in microglia cells[J].Neurosci Lett,2010,485(3):143-147.
[23]CARMELIET P,JAIN R K.Angiogenesis in cancer and other diseases[J].Nature,2000,407(6801):249.
[24]CHENG R,LI C,LI C,et al.The artemisinin derivative artesunate inhibits corneal neovascularization by inducing ROS-dependent apoptosis in vascular endothelial cells[J].Invest Ophthalmol Vis Sci,2013,54(5):3400-3409.
[25]DING H,WANG H,ZHAO Y,et al.Protective Effects of Baicalin on Aβ1-42-Induced Learning and Memory Deficit,Oxidative Stress,and Apoptosis in Rat[J].Cell Mol Neurobiol,2015,35(5):623-632.
[26]GAO Z,HUANG K,XU H.Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells[J].Pharmacological Research,2001,43(2):173-178.
[27]王雅芳,李婷,唐正海,等.中药黄芩的化学成分及药理研究进展[J].中华中医药学刊,2015,33(1):206-211.
[28]辛文妤,宋俊科,何国荣,等.黄芩素和黄芩苷的药理作用及机制研究进展[J].中国新药杂志,2013,22(6):647-653.
[29]VENIGALLA M,GYENGESI E,SHARMAN M J,et al.Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease[J].Neurochem Int,2015,95(8):63-74.
[30]ANDORN A C,BRITTON R S,BACON B R,et al.Ascorbate-stimulated lipid peroxidation and non-heme iron concentrations in Alzheimer disease[J].Mol Chem Neuropathol,1998,33(1):15-26.
[31]SUGIHARA N,ARAKAWA T,OHNISHI M,et al.Antiand pro-oxidative effects of flavonoids on metal-induced lipid hydroperoxide-dependent lipid peroxidation in cultured hepatocytes loaded with alpha-linolenic acid[J].Free Radical Biol Med,1999,27(11-12):1313.
[32]SOUZA L C,ANTUNES M S,FILHO C B,et al.Flavonoid Chrysin prevents age-related cognitive decline via attenuation of oxidative stress and modulation of BDNF levels in aged mouse brain[J].Pharmacol Biochem Be,2015(134):22-30.
[33]MORITA A,SOGA K,NAKAYAMA H,et al.Neuronal differentiation of human IPS cells induced by baicalin via regulation of b HLH gene expression[J].Biochem Bioph Res Co,2015,465(3):458-463.
[34]VENIGALLA M,GYENGESI E,SHARMAN M J,et al.Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease[J].Neurochem Int,2015,95(8):63-74.
[35]JEON S J,RHEE S Y,SEO J E,et al.Oroxylin A increases BDNF production by activation of MAPK-CREB pathway in rat primary cortical neuronal culture[J].Neurosci Res,2011,69(3):214.
[36]JEON S J,BAK H,SEO J,et al.Oroxylin A Induces BDNF Expression on Cortical Neurons through Adenosine A2A Receptor Stimulation:A Possible Role in Neuroprotection[J].Biomol Ther,2012,20(1):27.
[37]刘树玲,刘梅芳,朱宝亮.中草药活性成分治疗阿尔茨海默病的研究进展[J].医学综述,2010,16(18):107-109.
[38]赵宇红,李芳芳,曾宇.芹黄素对SAMP8小鼠学习记忆及突触可塑性的影响[J].中国老年学杂志,2015,35(15):4113-4116.
[39]CHO J,LEE H K.Wogonin inhibits excitotoxic and oxidative neuronal damage in primary cultured rat cortical cells[J].Eur J Pharmacol,2004,485(1-3):105-110.
[40]LOSI G,PUIA G,GARZON G,et al.Apigenin modulates GABAergic and glutamatergic transmission in cultured cortical neurons[J].Eur J Pharmacol,2004,502(1-2):41-46.
[41]GRESAARRIBAS N,SERRATOSA J,SAURA J,et al.Inhibition of CCAAT/enhancer binding proteinδexpression by chrysin in microglial cells Results in anti-inflammatory and neuroprotective effects[J].J Neurochem,2010,115(2):526-536.