黄芩苷的抗肿瘤作用及机制研究进展
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摘要
黄芩(Scutellaria baicalensis Georgi)是我国重要的大宗中药之一,产量大且用途广泛,黄芩苷(baicalin)是其中最主要的有效成分,属于黄酮类化合物。在中国传统医学中认为黄芩苷具有清热解毒、降压、抗病毒等功能。随着近年来的研究发现,黄芩苷在抗肿瘤等方面同样存在着诸多积极作用。对黄芩苷在抗肿瘤方面的作用进行了重点概述,以期扩展对黄芩苷药效的认识,为未来癌症的治疗提供新的思路。
Scutellaria baicalensis Georgi is one of the most important Chinese herbal medicines in China. It has a large production and a wide range of uses. Baicalin is one of the most important active ingredients and belongs to flavonoids. In traditional Chinese medicine,baicalin has the functions of clearing away heat,detoxifying,reducing blood pressure and antivirus. In recent years,it has been found that baicalin also plays an active role in antitumor. This article focused on the role of baicalin in the antitumor aspects,which was expected to expand the understanding of the efficacy of baicalin,and provide new ideas for the future treatment of cancer.
Scutellaria baicalensis Georgi is one of the most important Chinese herbal medicines in China. It has a large production and a wide range of uses. Baicalin is one of the most important active ingredients and belongs to flavonoids. In traditional Chinese medicine,baicalin has the functions of clearing away heat,detoxifying,reducing blood pressure and antivirus. In recent years,it has been found that baicalin also plays an active role in antitumor. This article focused on the role of baicalin in the antitumor aspects,which was expected to expand the understanding of the efficacy of baicalin,and provide new ideas for the future treatment of cancer.
引文
[1] Kim S J,Lee S M. Effect of baicalin on toll-like receptor 4-mediatedischemia/reperfusion inflammatory responses in alcoholic fatty liver condition[J]. Tocicol. Appl. Pharmacol.,2012,258(1):43-50.
[2] Kumari S,Puneet,Prasad S B,et al.. Cyclin D1 and cyclin E2are differentially expressed in gastric cancer[J]. Med. Oncol.,2016,33(5):40.
[3] Otto T,Sicinski P. Cell cycle proteins as promising targets in cancer therapy[J]. Nat. Rev. Cancer,2017,17(2):93-115.
[4] Gao J,Morgan W A,Sanchezmedina A,et al.. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells[J]. Toxicol. Appl.Pharmacol.,2011,254(3):221-228.
[5] Chao J I,Su W H. Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kirase and survivin associated with opposite role of p38 mitogen-activated protein kinase and AKT[J]. Mol. Cancer Therap.,2007,6(11):3039-3042.
[6] Wall N R,O’Connor D S,Plescia J,et al.. Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis[J]. Cancer Res.,2003,63(1):230-235.
[7] Bai Z,Wang H,Wang H. The effects of baicalin on the expression of TLR8,HIF-1α,PDGFβand pten of gastric cancer SGC-7901 cells[J]. Western J. Trad. Chin. Med.,2017,30(8):12-16.
[8] Wu H,Goel V,Haluska F G. PTEN signaling pathways in melanoma[J]. Oncogene,2003,22(20):3113-3122.
[9] Kong D,Zhang Y,Yamori T,et al.. Inhibitory activity of flavonoids against ClassⅠphosphatidylinositol 3-kinase isoforms[J]. Molecules,2011,16(6):5159-5167.
[10] Zhang H B,Lu P, Guo Q Y, et al.. Baicalein induces apoptosis in esophageal squamous cell carcinoma cells through modulation of the PI3K/Akt pathway[J]. Oncol. Lett.,2013,5(2):722-728.
[11]董明,侯俊明,高美花,等.黄芩苷对肝癌细胞株SMMC-7721裸鼠移植瘤生长抑制作用及其机制[J].现代肿瘤医学,2014,22(2):256-258.
[12]郭昱,霍瑞静,姚金峰.黄芩苷对肝癌细胞SMMC-7721 JAKSTAT信号通路STAT3的影响[J].世界华人消化杂志,2011,19(22):2363-2367.
[13] Booz G W,Day J N,Baker K M.Interplay between the cardiac renin angiotensin system and JAK-STAT signaling:role in cardiac hypertrophy,ischemia/reperfusion dysfunction, and heart failure[J]. J. Mol. Cell. Cardiol.,2002,34(11):1443-1453.
[14] Fletcher S,Turkson J,Gunning P T. Molecular approaches towards the inhibition of the signal transducer and activator of transcription 3(Stat3)protein[J]. ChemMedChem,2008,39(45):1159-1168.
[15] Elmore S. Apoptosis:A review of programmed cell death[J].Toxicol. Pathol.,2007,35(4):495-516.
[16]赵瑞杰,李引乾,王会,等.Caspase家族与细胞凋亡的关系[J].中国畜牧杂志,2010,46(17):73-78.
[17] Shieh D E,Cheng H Y,Yen M H,et al.. Baicalin-induced apoptosis is mediated by Bcl-2-dependent, but not p53-dependent,pathway in human leukemia cell lines[J]. Am. J.Chin. Med.,2006,34(02):245-261.
[18] Lu H F,Hsueh S C,Ho Y T,et al.. ROS mediates baicalin-induced apoptosis in human promyelocytic leukemia HL-60 cells through the expression of the Gadd153 and mitochondrial-dependent pathway[J]. Anticancer Res.,2007,27(1A):117-125.
[19] Chen F Q. Baicalin induces apoptosis of gastric cancer MGC-803 and BGC-823 cells through death receptor pathway[J].China Med. Abstr.(Int. Med.),2016,33(1):39-40.
[20] Duan D,Qin J,Liu J,et al.. The effects and molecular mechanisms of baicali on tumor proliferation and apoptosis of MG-63cell[J]. J. Modern Oncol.,2015,23(23):3391-3394.
[21]陈华江.基质金属蛋白酶及其抑制物与肿瘤侵袭转移的关系[J].国际肿瘤学杂志,2001,28(1):23-26.
[22] Itoh Y,Takamura A,Ito N, et al.. Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion[J]. EMBO J.,2014,20(17):4782-4793.
[23] Barun P Y,Mi L D,Ki K. DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-κB pathway[J]. Acta Biochim. Biophys. Sin.,2015,47(4):292-298.
[24] Kanayama H,Yokota K,Kurokawa Y,et al.. Prognostic values of matrix metalloproteinase-2 and tissue inhibitor of metalloprotienase-2 expression in bladder cancer[J]. Cancer,2015,82(7):1359-1366.
[25] Chetty C,Lakka S S,Praveen B,et al.. TIMP-3 suppresses tumor angiogenesis in MMP-2 downregulated lung cancer[J].Cancer Res.,2008,68(12):4736-4745.
[26] Ramos-Desimone N,Hahn-Dantona E, Sipley J, et al..Activation of matrix metalloproteinase-9(MMP-9)via a converging plasmin/stromelysin-1 cascade enhances tumor cell invasion[J]. J. Biol. Chem.,1999,274(19):13066-13076.
[27] Bhoopathi P,Chetty C,Kunigal S,et al.. Blockade of tumor growth due to MMP-9 inhibition is mediated by sequential activation ofβ1 integrin,ERK and NF-κB[J]. Eighth Intern. Confer. Intell. Syst. Design,2008,1(11):327-332.
[28] Chen Y J,Wei Y Y,Chen H T,et al.. Osteopontin increases migration and MMP-9 up-regulation viaαvβ3 integrin,FAK,ERK,and NF-κB-dependent pathway in human chondrosarcoma cells[J]. J. Cell. Physiol.,2010,221(1):98-108.
[29] Lakka S S,Gondi C N,Olivero W C,et al.. Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion,tumor growth and angiogenesis[J]. Oncogene,2004,23(27):4681-4689.
[30]张悦,符乔珊,刘韡,等.黄芩苷对宫颈癌He La细胞侵袭转移的抑制作用及其机制[J].西安交通大学学报,2016,37(4):599-603.
[31] Kumar B,Koul S,Petersen J,et al.. p38 mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity[J].Cancer Res.,2010,70(2):832-841.
[32]王熙熙.黄芩苷对人卵巢癌SKOV3细胞的抑制作用及其机制研究[D].北京:北京中医药大学,硕士学位论文,2017.
[33] Sebolt-Leopold J S,Herrera R. Targeting th mitogen-activated protein kinase cascade to treat cancer[J]. Nature Rev. Cancer,2004,4(12):937-947.
[34]孔卫平,孙冬霞,时志民,等.p-ERK-1及相关因子在子宫内膜癌中的表达及意义[J].中国热带医学,2013,13(3):270-272.
[35] Piette C,Depre Z,Roger T,et al.. The Dexamethasone-induced inhibition of proliferation,migration,and invasion in glioma cell lines is antagonized by macrophage migration inhibitory factor(MIF)and can be enhanced by specific MIF inhibitors[J]. J.Biol. Chem.,2009,284(47):32483-32492.
[36] Jing Y,Han Z,Zhang S,et al.. Epithelial-mesenchymal transition in tumor microenvironment[J]. Cell Biosci.,2011,1(1):29-29.
[37] Kalluri R,Weinberg R A.The basics of epithelial-mesenchymal transition[J]. J. Clin. Invest.,2009,119(6):1420-1428.
[38] Chung H,Choi H S,Seo E K,et al.. Baicalin and baicalein inhibit transforming growth factorβ1-mediated epithelial-mesenchymal transition in human breast epithelial cells[J]. Biochem. Biophys. Res. Commun.,2015,458(3):707-713.
[39] Wang Y,Wang H,Zhou R,et al.. Baicalin inhibits human osteosarcoma cells invasion,metastasis,and anoikis resistance by suppressing the transforming growth factor-β1-induced epithelial-to-mesenchymal transition[J]. Anti-cancer Drugs,2017,28(6):581-587.
[40] Mathew J L,Sirghi S.Vimentin induces changes in cell shape,moyility,and adhesion during the epithelial to mesenchymal transition[J]. FASEB J.,2010,24(6):1838-1851.
[41] Mansoorali K P, Prakash T, Kotresha D, et al..Cerebroprotective effect of Eclipta alba against global model of cerebral ischemia induced oxidative stress in rats[J].Phytomed. Intern. J. Phytother. Phytopharmacol.,2012,19(12):1108-1116.
[42] Xiong S S,Shi Y Y,Shi H P,et al.. Research status of reactive oxygen species and tumor[J]. Chin. J. Cancer Prevent.Treat.,2014,21(13):1045-1048.
[43] Ng T B,Liu F,Wang Z T. Antioxidative activity of natural products from plants[J]. Life Sci.,2000,66(8):709-723.
[44] Gao Z,Huang K,Yang X,et al.. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baocalensis Georgi[J]. Biochim. Biophys. Acta,1999,1472(3):643-650.
[45]谭廷华,刘爱芳.黄芩甙和芸香甙对·OH的清除作用[J].西安交通大学学报,1997,18(1):41-43.
[46] Cao Y,Mao X,Sun C,et al.. Baicalin attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-oxidative and anti-apoptotic pathway[J]. Brain Res. Bull.,2011,85(6):396-402.
[47] Zheng W X,Wang F,Cao X L,et al.. Baicalin protects PC-12cells from oxidative stress induced by hydrogen peroxide via anti-apoptotic effects[J]. Brain Injury,2014,28(2):227-234.
[48]李佳腊,张亚婷,谢飞.氢分子在癌症防治中的应用进展[J].生物技术进展,2016,6(3):174-178.
[49]夏娟,李冬,郑伟萍,等.炎症与肿瘤的关系研究进展[J].国际检验医学杂志,2013,34(1):63-65.
[50] Wang Y,Li Y,Shen B F,et al.. Inflammation:A driver for tumor development[J]. J. Intern. Parm. Res.,2014,41(1):63-67.
[51] Gao M,Zhang N,Li D,et al.. Baicalin plays an anti-inflammatory role through reducing nuclear factor-κB and p38 phosphorylation in Saureus-induced mastitis[J]. Intern. Immunopharmacol.,2013,16(2):125-130.
[52] Greten F R,Karin M. The IKK/NF-κB activation pathway——a target for prevention and treatment of cancer[J]. Cancer Lett.,2004,206(2):193-199.
[53] Yu Z,Zhang W,Kone B C. Signal transducers and activators of transcription 3(STAT3)inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factorκB[J]. Biochem. J.,2002,367(1):97-105.
[54] Lim H A,Lee E K,Ji M K,et al.. PPARγactivation by baicalin suppresses NF-κB-mediated inflammation in aged rat kidney[J]. Biogerontology,2012,13(2); 133-145.
[55]王倩,别玉龙,范文涛.加味黄芩汤对TNBS诱导的结肠炎大鼠肠道菌群结构及IL-6/STAT3信号通路的影响[J].陕西中医,2017,38(4):528-530.
[56] Li B Q,Fu T,Gong W H,et al.. The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines[J]. Immunopharmacology,2000,49(3):295-306.
[57] Luo W, Wang C Y, Jin L. Baicalin downregulates porphyromonas gingivalis lipopolysaccharide-upregulated IL-6and IL-8 expression in human oral keratinocytes by negative regulation of TLR signaling[J]. PLoS ONE,2012,7(12):e51008.
[58] Hoshino K,Takeuchi O,Kawai T,et al.. Toll-like receptor 4(TLR4)-deficient mice are hyporesponsive to lipopolysaccharide:Evidence for TLR4 as the Lps gene product[J]. J. Immunol.,1999,162(7):3749-3752.
[59] Feng J,Guo C,Zhu Y,et al.. Baicalin down regulates the expression of TLR4 and NFκB-p65 in colon tissue in mice with colitis induced by dextran sulfate sodium[J]. Int. J. Clin. Exp.Med.,2014,7(11):4063-4072.
[2] Kumari S,Puneet,Prasad S B,et al.. Cyclin D1 and cyclin E2are differentially expressed in gastric cancer[J]. Med. Oncol.,2016,33(5):40.
[3] Otto T,Sicinski P. Cell cycle proteins as promising targets in cancer therapy[J]. Nat. Rev. Cancer,2017,17(2):93-115.
[4] Gao J,Morgan W A,Sanchezmedina A,et al.. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells[J]. Toxicol. Appl.Pharmacol.,2011,254(3):221-228.
[5] Chao J I,Su W H. Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kirase and survivin associated with opposite role of p38 mitogen-activated protein kinase and AKT[J]. Mol. Cancer Therap.,2007,6(11):3039-3042.
[6] Wall N R,O’Connor D S,Plescia J,et al.. Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis[J]. Cancer Res.,2003,63(1):230-235.
[7] Bai Z,Wang H,Wang H. The effects of baicalin on the expression of TLR8,HIF-1α,PDGFβand pten of gastric cancer SGC-7901 cells[J]. Western J. Trad. Chin. Med.,2017,30(8):12-16.
[8] Wu H,Goel V,Haluska F G. PTEN signaling pathways in melanoma[J]. Oncogene,2003,22(20):3113-3122.
[9] Kong D,Zhang Y,Yamori T,et al.. Inhibitory activity of flavonoids against ClassⅠphosphatidylinositol 3-kinase isoforms[J]. Molecules,2011,16(6):5159-5167.
[10] Zhang H B,Lu P, Guo Q Y, et al.. Baicalein induces apoptosis in esophageal squamous cell carcinoma cells through modulation of the PI3K/Akt pathway[J]. Oncol. Lett.,2013,5(2):722-728.
[11]董明,侯俊明,高美花,等.黄芩苷对肝癌细胞株SMMC-7721裸鼠移植瘤生长抑制作用及其机制[J].现代肿瘤医学,2014,22(2):256-258.
[12]郭昱,霍瑞静,姚金峰.黄芩苷对肝癌细胞SMMC-7721 JAKSTAT信号通路STAT3的影响[J].世界华人消化杂志,2011,19(22):2363-2367.
[13] Booz G W,Day J N,Baker K M.Interplay between the cardiac renin angiotensin system and JAK-STAT signaling:role in cardiac hypertrophy,ischemia/reperfusion dysfunction, and heart failure[J]. J. Mol. Cell. Cardiol.,2002,34(11):1443-1453.
[14] Fletcher S,Turkson J,Gunning P T. Molecular approaches towards the inhibition of the signal transducer and activator of transcription 3(Stat3)protein[J]. ChemMedChem,2008,39(45):1159-1168.
[15] Elmore S. Apoptosis:A review of programmed cell death[J].Toxicol. Pathol.,2007,35(4):495-516.
[16]赵瑞杰,李引乾,王会,等.Caspase家族与细胞凋亡的关系[J].中国畜牧杂志,2010,46(17):73-78.
[17] Shieh D E,Cheng H Y,Yen M H,et al.. Baicalin-induced apoptosis is mediated by Bcl-2-dependent, but not p53-dependent,pathway in human leukemia cell lines[J]. Am. J.Chin. Med.,2006,34(02):245-261.
[18] Lu H F,Hsueh S C,Ho Y T,et al.. ROS mediates baicalin-induced apoptosis in human promyelocytic leukemia HL-60 cells through the expression of the Gadd153 and mitochondrial-dependent pathway[J]. Anticancer Res.,2007,27(1A):117-125.
[19] Chen F Q. Baicalin induces apoptosis of gastric cancer MGC-803 and BGC-823 cells through death receptor pathway[J].China Med. Abstr.(Int. Med.),2016,33(1):39-40.
[20] Duan D,Qin J,Liu J,et al.. The effects and molecular mechanisms of baicali on tumor proliferation and apoptosis of MG-63cell[J]. J. Modern Oncol.,2015,23(23):3391-3394.
[21]陈华江.基质金属蛋白酶及其抑制物与肿瘤侵袭转移的关系[J].国际肿瘤学杂志,2001,28(1):23-26.
[22] Itoh Y,Takamura A,Ito N, et al.. Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion[J]. EMBO J.,2014,20(17):4782-4793.
[23] Barun P Y,Mi L D,Ki K. DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-κB pathway[J]. Acta Biochim. Biophys. Sin.,2015,47(4):292-298.
[24] Kanayama H,Yokota K,Kurokawa Y,et al.. Prognostic values of matrix metalloproteinase-2 and tissue inhibitor of metalloprotienase-2 expression in bladder cancer[J]. Cancer,2015,82(7):1359-1366.
[25] Chetty C,Lakka S S,Praveen B,et al.. TIMP-3 suppresses tumor angiogenesis in MMP-2 downregulated lung cancer[J].Cancer Res.,2008,68(12):4736-4745.
[26] Ramos-Desimone N,Hahn-Dantona E, Sipley J, et al..Activation of matrix metalloproteinase-9(MMP-9)via a converging plasmin/stromelysin-1 cascade enhances tumor cell invasion[J]. J. Biol. Chem.,1999,274(19):13066-13076.
[27] Bhoopathi P,Chetty C,Kunigal S,et al.. Blockade of tumor growth due to MMP-9 inhibition is mediated by sequential activation ofβ1 integrin,ERK and NF-κB[J]. Eighth Intern. Confer. Intell. Syst. Design,2008,1(11):327-332.
[28] Chen Y J,Wei Y Y,Chen H T,et al.. Osteopontin increases migration and MMP-9 up-regulation viaαvβ3 integrin,FAK,ERK,and NF-κB-dependent pathway in human chondrosarcoma cells[J]. J. Cell. Physiol.,2010,221(1):98-108.
[29] Lakka S S,Gondi C N,Olivero W C,et al.. Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion,tumor growth and angiogenesis[J]. Oncogene,2004,23(27):4681-4689.
[30]张悦,符乔珊,刘韡,等.黄芩苷对宫颈癌He La细胞侵袭转移的抑制作用及其机制[J].西安交通大学学报,2016,37(4):599-603.
[31] Kumar B,Koul S,Petersen J,et al.. p38 mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity[J].Cancer Res.,2010,70(2):832-841.
[32]王熙熙.黄芩苷对人卵巢癌SKOV3细胞的抑制作用及其机制研究[D].北京:北京中医药大学,硕士学位论文,2017.
[33] Sebolt-Leopold J S,Herrera R. Targeting th mitogen-activated protein kinase cascade to treat cancer[J]. Nature Rev. Cancer,2004,4(12):937-947.
[34]孔卫平,孙冬霞,时志民,等.p-ERK-1及相关因子在子宫内膜癌中的表达及意义[J].中国热带医学,2013,13(3):270-272.
[35] Piette C,Depre Z,Roger T,et al.. The Dexamethasone-induced inhibition of proliferation,migration,and invasion in glioma cell lines is antagonized by macrophage migration inhibitory factor(MIF)and can be enhanced by specific MIF inhibitors[J]. J.Biol. Chem.,2009,284(47):32483-32492.
[36] Jing Y,Han Z,Zhang S,et al.. Epithelial-mesenchymal transition in tumor microenvironment[J]. Cell Biosci.,2011,1(1):29-29.
[37] Kalluri R,Weinberg R A.The basics of epithelial-mesenchymal transition[J]. J. Clin. Invest.,2009,119(6):1420-1428.
[38] Chung H,Choi H S,Seo E K,et al.. Baicalin and baicalein inhibit transforming growth factorβ1-mediated epithelial-mesenchymal transition in human breast epithelial cells[J]. Biochem. Biophys. Res. Commun.,2015,458(3):707-713.
[39] Wang Y,Wang H,Zhou R,et al.. Baicalin inhibits human osteosarcoma cells invasion,metastasis,and anoikis resistance by suppressing the transforming growth factor-β1-induced epithelial-to-mesenchymal transition[J]. Anti-cancer Drugs,2017,28(6):581-587.
[40] Mathew J L,Sirghi S.Vimentin induces changes in cell shape,moyility,and adhesion during the epithelial to mesenchymal transition[J]. FASEB J.,2010,24(6):1838-1851.
[41] Mansoorali K P, Prakash T, Kotresha D, et al..Cerebroprotective effect of Eclipta alba against global model of cerebral ischemia induced oxidative stress in rats[J].Phytomed. Intern. J. Phytother. Phytopharmacol.,2012,19(12):1108-1116.
[42] Xiong S S,Shi Y Y,Shi H P,et al.. Research status of reactive oxygen species and tumor[J]. Chin. J. Cancer Prevent.Treat.,2014,21(13):1045-1048.
[43] Ng T B,Liu F,Wang Z T. Antioxidative activity of natural products from plants[J]. Life Sci.,2000,66(8):709-723.
[44] Gao Z,Huang K,Yang X,et al.. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baocalensis Georgi[J]. Biochim. Biophys. Acta,1999,1472(3):643-650.
[45]谭廷华,刘爱芳.黄芩甙和芸香甙对·OH的清除作用[J].西安交通大学学报,1997,18(1):41-43.
[46] Cao Y,Mao X,Sun C,et al.. Baicalin attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-oxidative and anti-apoptotic pathway[J]. Brain Res. Bull.,2011,85(6):396-402.
[47] Zheng W X,Wang F,Cao X L,et al.. Baicalin protects PC-12cells from oxidative stress induced by hydrogen peroxide via anti-apoptotic effects[J]. Brain Injury,2014,28(2):227-234.
[48]李佳腊,张亚婷,谢飞.氢分子在癌症防治中的应用进展[J].生物技术进展,2016,6(3):174-178.
[49]夏娟,李冬,郑伟萍,等.炎症与肿瘤的关系研究进展[J].国际检验医学杂志,2013,34(1):63-65.
[50] Wang Y,Li Y,Shen B F,et al.. Inflammation:A driver for tumor development[J]. J. Intern. Parm. Res.,2014,41(1):63-67.
[51] Gao M,Zhang N,Li D,et al.. Baicalin plays an anti-inflammatory role through reducing nuclear factor-κB and p38 phosphorylation in Saureus-induced mastitis[J]. Intern. Immunopharmacol.,2013,16(2):125-130.
[52] Greten F R,Karin M. The IKK/NF-κB activation pathway——a target for prevention and treatment of cancer[J]. Cancer Lett.,2004,206(2):193-199.
[53] Yu Z,Zhang W,Kone B C. Signal transducers and activators of transcription 3(STAT3)inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factorκB[J]. Biochem. J.,2002,367(1):97-105.
[54] Lim H A,Lee E K,Ji M K,et al.. PPARγactivation by baicalin suppresses NF-κB-mediated inflammation in aged rat kidney[J]. Biogerontology,2012,13(2); 133-145.
[55]王倩,别玉龙,范文涛.加味黄芩汤对TNBS诱导的结肠炎大鼠肠道菌群结构及IL-6/STAT3信号通路的影响[J].陕西中医,2017,38(4):528-530.
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