苓桂术甘汤药理作用及其机制研究进展
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摘要
苓桂术甘汤临床广泛应用于由脾虚饮停引起的各种疾病,是温脾化饮法的代表方。古代医家对其组方论述也多不离脾虚饮停。现代研究发现,苓桂术甘汤组成成分大多含有抗炎、抗肿瘤以及调节免疫的作用。目前关于苓桂术甘汤的药理机制研究主要涵盖β淀粉样蛋白(Aβ)清除与抗神经炎症、调控脂质代谢和胰岛素抵抗、保护心肌细胞以及调节水液代谢。苓桂术甘汤可以通过调节Aβ关键转运蛋白的表达,包括低密度脂蛋白受体相关蛋白-1和晚期糖基化终末产物受体,促进Aβ清除,并且可以通过抑制小胶质细胞分泌白细胞介素(IL)-1β,IL-6和肿瘤坏死因子-α(TNF-α)等促炎因子减轻神经细胞炎症。该方还可通过调控脂联素、胰岛素和瘦素水平影响脂质代谢和胰岛素抵抗,进而对代谢综合征和非酒精性脂肪性肝病产生治疗作用。苓桂术甘汤对心肌细胞的保护机制主要涉及抑制核转录因子-κB(NF-κB)信号通路过度激活、上调Smad7蛋白表达和下调Smad3蛋白表达、调节NF-κB抑制蛋白激酶(IKK)/NF-κB抑制蛋白(IκB)/NF-κB信号通路,抑制炎症因子产生以及下调半胱氨酸蛋白酶(Caspase)-3和Caspase-8表达。此外,苓桂术甘汤还可调控水通道蛋白以影响机体水液代谢。该方还具有显著的抗氧化作用。中药复方与中医疾病证候的网络调节密切相关,借助以"疾病-靶点-药物"为特征的网络药理学完善"病-证-方"研究,有助于阐释脾虚饮停证的科学内涵以及温脾化饮法的生物学机制。
Linggui Zhugan Tang( LGZG),a representative of warming spleen to resolve fluid retention,is widely used in various diseases caused by spleen deficiency and fluid retention( SDFR). Ancient doctors mostly focused on the theme of SDFR to analysis the composition of LGZG. Modern research has now found that most of the components of LGZG contain anti-inflammatory,anti-tumor and immune-modulating effects. At present,the pharmacological research of LGZG mainly involves clearance of β-amyloid( Aβ) and anti-neuroinflammation,regulation of lipid metabolism and insulin resistance,protection of myocardial cells and regulation of liquid metabolism as follow. LGZG can promote the clearance of Aβ by regulating the expression of Aβ transporters,including low-density lipoprotein receptor-associated protein-1 and terminal glycosylation product receptors,as well as reduce the inflammation of nerve cells by inhibiting the secretion of pro-inflammatory factors such as interleukin( IL)-1β,IL-6 and tumor necrosis factor-α( TNF-α) by microglia. The prescription can also affect the lipid metabolism and insulin resistance by regulating the levels of adiponectin,insulin and leptin,thus producing therapeutic effects on metabolic syndrome and non-alcoholic fatty liver disease. The protective mechanism of LGZG on myocardial cells mainly contains inhibition of the over-activation of nuclear transcription factor-κB( NF-κB)signaling pathway, up-regulation of Smad7 expression and down-regulation of Smad3 expression,regulation of inhibitor of nuclear factor kappa-B kinase( IKK)/NF-κB inhibitor( IκB)/NF-κB signaling pathway,inhibition of inflammatory factor production,and down-regulation of Caspase-3 and Caspase-8 expression. In addition,LGZG can also regulate aquaporins to affect water metabolism. And it also has significant antioxidant effects. As is known to all,the functional mechanism of traditional Chinese medicine( TCM) compound is closely related to the network regulation of TCM disease syndromes. Considered from this angle,it is helpful to carry out the " disease-syndromeformula" research by means of network pharmacology characterized by " disease-target-drug ",thus organically exploring the relationship between LGZG and SDFR from the microscopic perspective,and helping to explain the scientific connotation of SDFR and the biological mechanism of warming spleen to resolve fluid retention.
Linggui Zhugan Tang( LGZG),a representative of warming spleen to resolve fluid retention,is widely used in various diseases caused by spleen deficiency and fluid retention( SDFR). Ancient doctors mostly focused on the theme of SDFR to analysis the composition of LGZG. Modern research has now found that most of the components of LGZG contain anti-inflammatory,anti-tumor and immune-modulating effects. At present,the pharmacological research of LGZG mainly involves clearance of β-amyloid( Aβ) and anti-neuroinflammation,regulation of lipid metabolism and insulin resistance,protection of myocardial cells and regulation of liquid metabolism as follow. LGZG can promote the clearance of Aβ by regulating the expression of Aβ transporters,including low-density lipoprotein receptor-associated protein-1 and terminal glycosylation product receptors,as well as reduce the inflammation of nerve cells by inhibiting the secretion of pro-inflammatory factors such as interleukin( IL)-1β,IL-6 and tumor necrosis factor-α( TNF-α) by microglia. The prescription can also affect the lipid metabolism and insulin resistance by regulating the levels of adiponectin,insulin and leptin,thus producing therapeutic effects on metabolic syndrome and non-alcoholic fatty liver disease. The protective mechanism of LGZG on myocardial cells mainly contains inhibition of the over-activation of nuclear transcription factor-κB( NF-κB)signaling pathway, up-regulation of Smad7 expression and down-regulation of Smad3 expression,regulation of inhibitor of nuclear factor kappa-B kinase( IKK)/NF-κB inhibitor( IκB)/NF-κB signaling pathway,inhibition of inflammatory factor production,and down-regulation of Caspase-3 and Caspase-8 expression. In addition,LGZG can also regulate aquaporins to affect water metabolism. And it also has significant antioxidant effects. As is known to all,the functional mechanism of traditional Chinese medicine( TCM) compound is closely related to the network regulation of TCM disease syndromes. Considered from this angle,it is helpful to carry out the " disease-syndromeformula" research by means of network pharmacology characterized by " disease-target-drug ",thus organically exploring the relationship between LGZG and SDFR from the microscopic perspective,and helping to explain the scientific connotation of SDFR and the biological mechanism of warming spleen to resolve fluid retention.
引文
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[2]陈亦人.伤寒论译释[M].上海科学技术出版社,2010:424-428.
[3] YU B,ZHOU C,ZHANG J,et al. Latest study on the relationship between pathological process of inflammatory injury and the syndrome of spleen deficiency and Fluid retention in Alzheimer's disease[J]. Evid Based Complement Alternat Med,2014,2014(4):743541.
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[5] HU Q,YU B,CHEN Q,et al. Effect of Linguizhugan decoction on neuro inflammation and expression disorder of the amyloid betarelated transporters RAGE and LRP-1in a rat model of Alzheimer's disease[J]. Mol Med Rep,2018,17(1):827-834.
[6]宋宗华,戴舒佳,黎辉琴,等.苓桂术甘汤配伍机制研究[J].中国中药杂志,2002,(10):43-45.
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[9]赵玉娇,高耀,周玉枝,等.白术在神经精神系统疾病中的药理作用及机制研究进展[J].中草药,2017,48(21):4546-4551.
[10]姜雪,孙森凤,王悦,等.甘草药理作用研究进展[J].化工时刊,2017,31(7):25-28.
[11]李兰兰,王昕钰,任建功.代谢综合征各组分与炎症因子相关性研究进展[J].世界最新医学信息文摘,2019,19(11):33-34.
[12]黄江荣,杜亚明,鄢进,等.加味苓桂术甘汤对代谢综合征大鼠血清抵抗素、脂联素、胰岛素、胰岛素抵抗的影响[J].中国实验方剂学杂志,2013,19(6):227-230.
[13]卢文艺,刘莲,黄蔚,等.加味苓桂术甘汤对代谢综合征大鼠抗氧化作用及脂联素表达的影响[J].中国实验方剂学杂志,2016,22(10):97-101.
[14] YAO L,WEI J,SHI S,et al. Modified Lingguizhugan decoction incorporated with dietary restriction and exercise ameliorates hyperglycemia,hyperlipidemia and hypertension in a rat model of the metabolic syndrome[J]. BMC Complement Altern Med,2017,17(1):132.
[15]郭亮,汤其群.非酒精性脂肪肝发病机制和治疗的研究进展[J].生命科学,2018,30(11):1165-1172.
[16] ZHU M,HAO S,LIU T,et al. Lingguizhugan decoction improves non-alcoholic fatty liver disease by altering insulin resistance and lipid metabolism related genes:a whole trancriptome study by RNA-Seq[J]. Oncotarget,2017,8(47):82621-82631.
[17] YANG L,LIN W,Nugent C A,et al. Lingguizhugan decoction protects against high-fat-diet-induced nonalcoholic fatty liver disease by alleviating oxidative stress and activating cholesterol secretion[J]. Int J Genomics,2017,2017(9):1-12.
[18]毛堂友,韩海啸,赵唯含,等.苓桂术甘汤对NASH大鼠肝组织DGAT2、PKCε的作用研究[J].中国中西医结合消化杂志,2016,24(2):87-91.
[19]郭一,李军祥,毛堂友,等.苓桂术甘汤与茵陈蒿汤合方对非酒精性脂肪性肝炎大鼠Nrf2/ARE信号通路的影响[J].中国实验方剂学杂志,2017,23(16):108-113.
[20]刘立萍,李然,张立德,等.苓桂术甘汤对瘦素基因缺陷ob/ob小鼠肝FXR/FGF15/SHP途径的影响[J].中国实验方剂学杂志,2018,24(22):107-111.
[21]王延博,李宇球,王蓓,等.心力衰竭炎症标志物研究进展[J].心血管病学进展,2018,39(6):983-987.
[22] HUANG J,WANG L, SHI H,et al. Effect of Lingguizhugan decoction on myocardial nuclear factor kappa B protein expression in rats with chronic heart failure[J]. J Tradit Chin Med,2013,33(3):343-348.
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