

浏览全部资源
扫码关注微信
中国药科大学 中药学院,南京 211198
Received:18 March 2020,
Published Online:25 July 2020,
Published:20 November 2020
移动端阅览
孙宁远,朱雪林,陈君.丹参化学成分抗纤维化药理作用及机制研究进展[J].中国实验方剂学杂志,2020,26(22):201-208.
SUN Ning-yuan,ZHU Xue-lin,CHEN Jun.Research Progress of Anti-fibrosis Pharmacological Effect and Mechanisms of Chemical Components in Salviae Miltiorrhizae Radix et Rhizoma[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(22):201-208.
孙宁远,朱雪林,陈君.丹参化学成分抗纤维化药理作用及机制研究进展[J].中国实验方剂学杂志,2020,26(22):201-208. DOI: 10.13422/j.cnki.syfjx.20201870.
SUN Ning-yuan,ZHU Xue-lin,CHEN Jun.Research Progress of Anti-fibrosis Pharmacological Effect and Mechanisms of Chemical Components in Salviae Miltiorrhizae Radix et Rhizoma[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(22):201-208. DOI: 10.13422/j.cnki.syfjx.20201870.
纤维化是以成纤维细胞活化与细胞外基质异常增多和过度沉积为特征的病理过程,可发生于多种器官,持续进展可致器官结构破坏和功能减退乃至衰竭,严重威胁人类健康和生命。由于纤维化病理机制的复杂性,目前临床上仍缺乏有效的治疗药物。中药丹参为唇形科植物丹参的干燥根及根茎,是常用的活血化瘀药。现代药理学研究表明,丹参中的丹参酮类和丹酚酸类成分具有抗氧化、抗炎、抑制胶原纤维产生和促进纤维蛋白降解、抑制细胞增殖等多方面作用,在防治组织器官纤维化方面具有良好的应用前景。该文结合最新研究进展,对丹参中主要成分的抗纤维化药效和作用机制进行综述,以期为丹参的进一步研究和应用提供参考。
Fibrosis is a pathological feature of most chronic inflammatory diseases, which is pathologically characterized by activation of fibroblasts and deposition of extracellular matrix components. Fibrosis affects nearly every tissue in the body. If highly progressive, the fibrotic process eventually leads to organ malfunction and even death. Due to the complexity of the pathological mechanism of fibrosis, there is still a lack of effective therapeutic drugs. Salviae Miltiorrhizae Radix et Rhizoma, dry roots and rhizomes of
Salvia miltiorrhiza
, is a kind of traditional Chinese medicines for activating blood and removing stasis. Modern pharmacological studies have shown that the tanshinones and salvianolic acids in Salviae Miltiorrhizae Radix et Rhizoma have a wide range of anti-fibrosis effects, such as inhibiting the production of collagen fibers, promoting the degradation of fibrin, and inhibiting cell proliferation. In this review, pharmacological actions and mechanisms of active ingredients of Salviae Miltiorrhizae Radix et Rhizoma were summarized to provide references for the further development and utilization of Salviae Miltiorrhizae Radix et Rhizoma.
刘欣梦 , 刘伟丽 , 钱令嘉 . 重要脏器纤维化病变治疗药物的研究进展 [J]. 中国药理学与毒理学杂志 , 2014 ,( 4 ): 587 - 593 .
KENDALL R T , FEGHALI-BOSTWICK C A . Fibroblasts in fibrosis:novel roles and mediators [J]. Front Pharmacol , 2014 , 5 : 123 .
WANG L , LU W , GAO Y H , et al . Anluohuaxianwan Alleviates carbon tetrachloride-induced hepatic fibrosis in rats through upregulation of peroxisome proliferator‑activated receptor-gamma and downregulation of nuclear factor-kappa B/I κ B α signaling pathway [J]. World J Tradit Chin Med , 2019 , 5 ( 2 ): 95 - 103 .
ROCKEY D C , BELL P D , HILL J A , et al . Fibrosis-a common pathway to organ injury and failure [J]. N Engl J Med , 2015 , 372 ( 12 ): 1138 - 1149 .
程苗苗 , 赵雅楠 , 刘雪艳 , 等 . 转化生长因子 β (TGF- β )对CD4 + T细胞的调节作用及与免疫相关疾病的关系 [J]. 细胞与分子免疫学杂志 , 2016 , 32 ( 9 ): 1288 - 1291 .
SHI M , ZHU J , WANG R , et al . Latent TGF- β structure and activation [J]. Nature , 2011 , 474 ( 7351 ): 343 - 349 .
杜冠华 , 王月华 , 张冉 , 等 . 多成分多靶点是对中药作用机制的表面认识 [J]. 世界科学技术―中医药现代化) , 2009 , 11 ( 4 ): 480 - 484 .
张美军 , 杨胜辉 . 中医药治疗肝纤维化研究进展 [J]. 湖南中医杂志 , 2019 , 35 ( 10 ): 173 - 176 .
郑琦 , 樊慧婷 , 张英 , 等 . 丹参化学成分分析及其抗肿瘤药理作用的研究进展 [J]. 中华中医药学刊 , 2020 , 38 ( 4 ): 112 - 116 .
HIGASHI T , FRIEDMAN S L , HOSHIDA Y . Hepatic stellate cells as key target in liver fibrosis [J]. Adv Drug Deliv Rev , 2017 , 121 : 27 - 42 .
SHU M , HU X R , HUNG Z A , et al . Effects of tanshinone Ⅱ A on fibrosis in a rat model of cirrhosis through heme oxygenase-1,inflammation,oxidative stress and apoptosis [J]. Mol Med Rep , 2016 , 13 ( 4 ): 3036 - 3042 .
WANG R , WANG J , SONG F , et al . Tanshinol ameliorates ccl 4 -induced liver fibrosis in rats through the regulation of Nrf2/HO-1 and NF- κ B/I κ B α signaling pathway [J]. Drug Des Devel Ther , 2018 , 12 : 1281 - 1292 .
ZHANG X , MA Z , LIANG Q , et al . Tanshinone Ⅱ A exerts protective effects in a LCA-induced cholestatic liver model associated with participation of pregnane X receptor [J]. J Ethnopharmacol , 2015 , 164 : 357 - 367 .
PENG R , WANG S , WANG R , et al . Antifibrotic effects of tanshinol in experimental hepatic fibrosis by targeting PI3K/Akt/mTOR/p70S6K1 signaling pathways [J]. Discov Med , 2017 , 23 ( 125 ): 81 - 94 .
刘永刚 , 陈厚昌 , 蒋毅萍 . 丹参酮Ⅱ A 对四氯化碳致大鼠肝纤维化的实验研究 [J]. 中药材 , 2002 ,( 1 ): 31 - 33 .
张卫平 . 中医药抗脏器纤维化实验研究进展 [J]. 中国中医急症 , 2011 , 20 ( 6 ): 946 - 948 .
GE M , LIU H , ZHANG Y , et al . The anti-hepatic fibrosis effects of dihydrotanshinone I are mediated by disrupting the yes-associated protein and transcriptional enhancer factor D2 complex and stimulating autophagy [J]. Br J Pharmacol , 2017 , 174 ( 10 ): 1147 - 1160 .
HIGASHI T , FRIEDMAN S L , HOSHIDA Y . Hepatic stellate cells as key target in liver fibrosis [J]. Adv Drug Deliv Rev , 2017 , 121 : 27 - 42 .
SON G , HINES L N , LINDQUIST J , et al . Inhibition of phosphatidylinositol 3-kinase signaling in hepatic stellate cells blocks the progression of hepatic fibrosis [J]. Hepatology , 2009 , 50 ( 5 ): 1512 - 1523 .
WANG R , SONG F , LI S , et al . Salvianolic acid A attenuates CCl 4 -induced liver fibrosis by regulating the PI3K/AKT/mTOR,Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways [J]. Drug Des Devel Ther , 2019 , 13 : 1889 - 1900 .
ZHANG W , PING J , ZHOU Y , et al . Salvianolic acid B inhibits activation of human primary hepatic stellate cells through downregulation of the myocyte enhancer factor 2 signaling pathway [J]. Front Pharmacol , 2019 , 10 : 322 .
CHOI S S , SYN W K , KARACA G F , et al . Leptin promotes the myofibroblastic phenotype in hepatic stellate cells by activating the hedgehog pathway [J]. J Biol Chem , 2010 , 285 ( 47 ): 36551 - 36560 .
YU F , LU Z , CHEN B , et al . Salvianolic acid B-induced microRNA-152 inhibits liver fibrosis by attenuating DNMT1-mediated Patched1 methylation [J]. J Cell Mol Med , 2015 , 19 ( 11 ): 2617 - 2632 .
张笑菲 , 高卓维 , 吕志平 , 等 . 丹参酮Ⅱ A 抑制肝纤维化作用机制的研究进展 [J]. 山东医药 , 2018 , 58 ( 28 ): 86 - 89 .
张翼宙 , 卢冬冬 , 董颖 , 等 . 丹参酮Ⅱ A 对大鼠肝纤维化的干预作用及其调控AngⅡ的分子机制 [J]. 浙江中医药大学学报 , 2017 , 41 ( 1 ): 1 - 10 .
JIN Q , JIANG S , WU Y L , et al . Hepatoprotective effect of cryptotanshinone from Salvia miltiorrhiza in D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure [J]. Phytomedicine , 2014 , 21 ( 2 ): 141 - 147 .
张旭 , 王煜 , 马娟 , 等 . 内质网应激介导的细胞凋亡在肝纤维化发生发展中的作用 [J]. 临床肝胆病杂志 , 2015 , 31 ( 9 ): 1537 - 1539 .
ZHU J , WANG R , XU T , et al . Salvianolic acid A attenuates endoplasmic reticulum stress and protects against cholestasis-induced liver fibrosis via the SIRT1/HSF1 pathway [J]. Front Pharmacol , 2018 , 9 : 1277 .
QIANG G F , YANG X Y , XUAN Q , et al . Salvianolic acid A prevents the pathological progression of hepatic fibrosis in high-fat diet-fed and streptozotocin-induced diabetic rats [J]. Am J Chin Med , 2014 , 42 ( 5 ): 1183 - 1198 .
JIANG Y , YOU F , ZHU J , et al . Cryptotanshinone ameliorates radiation-induced lung injury in rats [J]. Evid Based Complement Alternat Med , 2019 , 5 : 1 - 14 .
TANG H Y , HE H Y , JI H , et al . Tanshinone Ⅱ A ameliorates bleomycin-induced pulmonary fibrosis and inhibits transforming growth factor-beta-dependent epithelial to mesenchymal transition [J]. J Surg Res , 2015 , 197 ( 1 ): 167 - 175 .
FENG F , LI N , CHENG P , et al . Tanshinone Ⅱ A attenuates silica-induced pulmonary fibrosis via inhibition of TGF- β 1 -Smad signaling pathway [J]. Biomed Pharmacother , 2020 , 121 : 109586 .
FENG F F , CHENG P , XU S H , et al . Tanshinone Ⅱ A attenuates silica-induced pulmonary fibrosis via Nrf2-mediated inhibition of EMT and TGF- β 1 /Smad signaling [J]. Chem Biol Interact , 2020 , 319 : 109024 .
BOCCHINO M , AGNESE S , FAGONE E , et al . Reactive oxygen species are required for maintenance and differentiation of primary lung fibroblasts in idiopathic pulmonary fibrosis [J]. PLoS One , 2010 , 5 ( 11 ): e14003 .
陈道南 , 田锐 . 氧化应激与肺纤维化 [J]. 国际呼吸杂志 , 2019 , 39 ( 24 ): 1898 - 1906 .
FENG F F , CHENG P , ZHANG H , et al . The protective role of tanshinone IIA in silicosis rat model via TGF- β 1 /Smad signaling suppression,NOX4 inhibition and Nrf2/ARE signaling activation [J]. Drug Des Devel Ther , 2019 , 13 : 4275 - 4290 .
LIU B , CAO B , ZHANG D , et al . Salvianolic acid B protects against paraquat-induced pulmonary injury by mediating Nrf2/Nox4 redox balance and TGF- β 1 /Smad3 signaling [J]. Toxicol Appl Pharmacol , 2016 , 309 : 111 - 120 .
杨雪梅 , 王兴胜 , 崔社怀 . 肌成纤维细胞在肺纤维化中的来源和作用 [J]. 国际病理科学与临床杂志 , 2008 , 28 ( 1 ): 54 - 58 .
王保兰 . EMT、TGF- β 1 、AngⅡ与器官纤维化发生机制的研究进展 [J]. 医学综述 , 2015 , 21 ( 22 ): 4072 - 4074 .
HOYLES R K , DERRETT-SMITH E C , KHAN K , et al . An essential role for resident fibroblasts in experimental lung fibrosis is defined by lineage-specific deletion of high-affinity type Ⅱ transforming growth factor β receptor [J]. Am J Respir Crit Care Med , 2011 , 183 ( 2 ): 249 - 261 .
AN L , PENG L Y , SUN N Y , et al . Tanshinone Ⅱ A activates nuclear factor-erythroid 2-related factor 2 to restrain pulmonary fibrosis via regulation of redox homeostasis and glutaminolysis [J]. Antioxid Redox Signal , 2019 , 30 ( 15 ): 1831 - 1848 .
PAN Y , FU H , KONG Q , et al . Prevention of pulmonary fibrosis with salvianolic acid A by inducing fibroblast cell cycle arrest and promoting apoptosis [J]. J Ethnopharmacol , 2014 , 155 ( 3 ): 1589 - 1596 .
ZHANG M , CAO S R , ZHANG R , et al . The inhibitory effect of salvianolic acid B on TGF- β 1 -induced proliferation and differentiation in lung fibroblasts [J]. Exp Lung Res , 2014 , 40 ( 4 ): 172 - 185 .
LIU Q M , SHI X G , TANG L Y , et al . Salvianolic acid B attenuates experimental pulmonary inflammation by protecting endothelial cells against oxidative stress injury [J]. Eur J Pharmacol , 2018 , 840 : 9 - 19 .
范沐霞 , 赵塔娜 , 王丽敏 , 等 . 姜黄素抗纤维化研究进展 [J]. 中医学报 , 2019 , 34 ( 11 ): 2343 - 2348 .
WANG W , ZHOU P H , HU W , et al . Cryptotanshinone hinders renal fibrosis and epithelial transdifferentiation in obstructive nephropathy by inhibiting TGF- β 1 /Smad3/integrin β 1 signal [J]. Oncotarget , 2017 , 9 ( 42 ): 26625 - 26637 .
WANG W , WANG X , ZHANG X S , et al . Cryptotanshinone attenuates oxidative stress and inflammation through the regulation of Nrf-2 and NF- κ B in mice with unilateral ureteral obstruction [J]. Basic Clin Pharmacol Toxicol , 2018 , 123 ( 6 ): 714 - 720 .
ZHANG H F , WANG Y L , GAO C , et al . Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF- κ B and p38 MAPK signaling pathways in 5/6 nephrectomized rats [J]. Acta Pharmacol Sin , 2018 , 39 ( 12 ): 1855 - 1864 .
ZHANG H F , WANG J H , WANG Y L , et al . Salvianolic acid A protects the kidney against oxidative stress by activating the Akt/GSK-3 β /Nrf2 signaling pathway and inhibiting the NF- κ B signaling pathway in 5/6 nephrectomized rats [J]. Oxid Med Cell Longev , 2019 , doi: 10.1155/2019/2853534 http://dx.doi.org/10.1155/2019/2853534 .
HO J . The regulation of apoptosis in kidney development:implications for nephron number and pattern? [J]. Front Pediatr , 2014 , 2 : 128 .
陈莎莎 , 李均 . 丹参酮Ⅱ A 抗肾间质纤维化作用机制的研究进展 [J]. 山东医药 , 2019 , 59 ( 14 ): 109 - 111 .
XU Y M , DING G H , HUANG J , et al . Tanshinone Ⅱ A pretreatment attenuates ischemia/reperfusion-induced renal injury [J]. Exp Ther Med , 2016 , 12 ( 4 ): 2741 - 2746 .
杨紫依 , 陈刚 , 朱芸霄 , 等 . 丹参酮Ⅱ A 对缺氧/复氧损伤肾小管上皮细胞的作用及机制研究 [J]. 重庆医科大学学报 , 2018 , 43 ( 11 ): 1427 - 1432 .
YAN X J , JIANG Z Q , BI L , et al . Salvianolic acid A attenuates TNF- α - and D-GalN-induced ER stress-mediated and mitochondrial-dependent apoptosis by modulating Bax/Bcl-2 ratio and calcium release in hepatocyte L02 cells [J]. Naunyn Schmiedebergs Arch Pharmacol , 2015 , 388 ( 8 ): 817 - 830 .
LO S H , HSU C T , NIU H S , et al . Cryptotanshinone inhibits STAT3 signaling to alleviate cardiac fibrosis in type 1-like diabetic rats [J]. Phytother Res , 2017 , 31 ( 4 ): 638 - 646 .
MA S T , YANG D C , WANG K Y , et al . Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in mice associated with upregulation and activation of matrix metalloproteinase-2 [J]. Mol Med Rep , 2012 , 6 ( 1 ): 145 - 150 .
MA Y Z , LI H , YUE Z B , et al . Cryptotanshinone attenuates cardiac fibrosis via downregulation of COX-2,NOX-2,and NOX-4 [J]. J Cardiovasc Pharmacol , 2014 , 64 ( 1 ): 28 - 37 .
WANG C H , LUO H , XU Y , et al . Salvianolic acid B-alleviated angiotensin Ⅱ induces cardiac fibrosis by suppressing NF- κ B pathway in vitro [J]. Med Sci Monit , 2018 , 24 : 7654 - 7664 .
HE H B , YANG X Z , SHI M Q , et al . Comparison of cardioprotective effects of salvianolic acid B and benazepril on large myocardial infarction in rats [J]. Pharmacol Rep , 2008 , 60 ( 3 ): 369 - 381 .
FANG J , XU S W , WANG P , et al . Tanshinone Ⅱ A attenuates cardiac fibrosis and modulates collagen metabolism in rats with renovascular hypertension [J]. Phytomedicine , 2010 , 18 ( 1 ): 58 - 64 .
冯俊 , 陈华文 , 李树生 . 丹参酮Ⅱ A 对慢性心力衰竭心肌重构的影响及其机制研究 [J]. 中国中医急症 , 2015 , 24 ( 12 ): 2069 - 2071 .
DAI J P , ZHU D X , SHENG J T , et al . Inhibition of tanshinone Ⅱ A ,salvianolic acid A and salvianolic acid B on areca nut extract-induced oral submucous fibrosis in vitro [J]. Molecules , 2015 , 20 ( 4 ): 6794 - 6807 .
LIU Q , LU J , LIN J , et al . Salvianolic acid B attenuates experimental skin fibrosis of systemic sclerosis [J]. Biomed Pharmacother , 2019 , 110 : 546 - 553 .
JIANG Y , HU F F , LI Q , et al . Tanshinone Ⅱ A ameliorates the bleomycin-induced endothelial-to-mesenchymal transition via the Akt/mTOR/p70S6K pathway in a murine model of systemic sclerosis [J]. Int Immunopharmacol , 2019 , 77 : 105968 .
0
Views
16
下载量
11
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621