-
纤维化是一种由器官慢性损伤或炎症反应引起的病理变化,其主要特征是细胞外基质(ECM)的过度积累,可见于心、肺、肝、肾、皮肤等多种组织器官,纤维化持续进展可导致组织结构破坏及器官功能障碍,最终引起器官衰竭[1]。尽管各组织器官的纤维化发病机制不尽相同,但其基本过程大抵相似,由器官损伤引起炎症免疫反应,进而激活局部肌成纤维细胞,降低组织收缩力,促进炎症介质的分泌和ECM的合成,从而逐步发展为纤维化。重要脏器的纤维化严重影响人类的健康,是目前世界医学的研究难题。
隐丹参酮(CTS)是一种从唇形科植物丹参Salvia miltiorrhiza Bge的干燥根和根茎中提取的脂溶性二萜类蒽醌化合物,具有抗炎[2]、抗肿瘤[3]、抗菌[4]、神经保护[5]、心血管保护[6]等多种药理活性,近年来研究发现其还具有良好的抗组织纤维化作用[7-9]。目前研究显示,隐丹参酮的抗纤维化作用机制主要与信号转导和转录激活因子3(signal transduction and transcriptional activator 3, STAT3)、转化生长因子β(transforming growth factor-beta, TGFβ)和核因子κB(nuclear factor kappa-B, NF-κB)信号通路的抑制作用有关[7, 9,10]。本文主要就隐丹参酮对心、肺、肝、肾、皮肤等多种组织器官纤维化的治疗作用及其机制进行综述,为隐丹参酮的药物研究提供参考。
Research progress of cryptotanshinone on anti-fibrosis and its mechanism
-
摘要: 隐丹参酮(CTS)作为一种高效低毒的天然化合物,在各器官组织中具有良好的抗纤维化作用,但目前其作用机制尚未明确,且无系统的文献综述对其抗纤维化潜在机制进行描述。笔者综述了隐丹参酮治疗各脏器纤维化的疗效及其机制,并提出了未来展望。Abstract: As a natural compound with high efficiency and low toxicity, cryptotanshinone (CTS) has a good anti-fibrosis effect in various organs and tissues. However, its mechanism of action has not been clearly defined, and there is no systematic literature review to describe its potential anti-fibrosis mechanism. The efficacy and mechanism of cryptotanshinone in the treatment of fibrosis in various organs were summarized and the use prospects were put forward in this paper.
-
Key words:
- cryptotanshinone /
- renal fibrosis /
- pulmonary fibrosis /
- cardiac fibrosis /
- liver fibrosis /
- mechanism
-
[1] WYNN T A, RAMALINGAM T R. Mechanisms of fibrosis: therapeutic translation for fibrotic disease[J]. Nat Med,2012,18(7):1028-1040. doi: 10.1038/nm.2807 [2] LIU H B, ZHAN X Y, XU G, et al. Cryptotanshinone specifically suppresses NLRP3 inflammasome activation and protects against inflammasome-mediated diseases[J]. Pharmacol Res,2021,164:105384. doi: 10.1016/j.phrs.2020.105384 [3] HAN Z, LIU S, LIN H S, et al. Inhibition of murine hepatoma tumor growth by cryptotanshinone involves TLR7-dependent activation of macrophages and induction of adaptive antitumor immune defenses[J]. Cancer Immunol Immunother,2019,68(7):1073-1085. doi: 10.1007/s00262-019-02338-4 [4] CHA J D, LEE J H, CHOI K M, et al. Synergistic effect between cryptotanshinone and antibiotics against clinic methicillin and vancomycin-resistant Staphylococcus aureus[J]. Evid Based Complement Alternat Med,2014,2014:450572. [5] MAO Y F, QU Y, WANG Q D. Cryptotanshinone reduces neurotoxicity induced by cerebral ischemia-reperfusion injury involving modulation of microglial polarization[J]. Restor Neurol Neurosci,2021,39(3):209-220. [6] ZHANG Y P, LUO F, ZHANG H X, et al. Cryptotanshinone ameliorates cardiac injury and cardiomyocyte apoptosis in rats with coronary microembolization[J]. Drug Dev Res,2021,82(4):581-588. doi: 10.1002/ddr.21777 [7] WANG W, ZHOU P H, HU W, et al. Cryptotanshinone hinders renal fibrosis and epithelial transdifferentiation in obstructive nephropathy by inhibiting TGF-β1/Smad3/integrin β1 signal[J]. Oncotarget,2017,9(42):26625-26637. [8] 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. doi: 10.1097/FJC.0000000000000086 [9] ZHANG Y T, LU W T, ZHANG X L, et al. Cryptotanshinone protects against pulmonary fibrosis through inhibiting Smad and STAT3 signaling pathways[J]. Pharmacol Res,2019,147:104307. doi: 10.1016/j.phrs.2019.104307 [10] WANG W, WANG X, ZHANG X S, et al. Cryptotanshinone attenuates oxidative stress and inflammation through the regulation of nrf-2 and NF-κB in mice with unilateral ureteral obstruction[J]. Basic Clin Pharmacol Toxicol,2018,123(6):714-720. doi: 10.1111/bcpt.13091 [11] LIU M R, LÓPEZ DE JUAN ABAD B, CHENG K. Cardiac fibrosis: Myofibroblast-mediated pathological regulation and drug delivery strategies[J]. Adv Drug Deliv Rev,2021,173:504-519. doi: 10.1016/j.addr.2021.03.021 [12] VERMOT A, PETIT-HÄRTLEIN I, SMITH S M E, et al. NADPH oxidases (NOX): an overview from discovery, molecular mechanisms to physiology and pathology[J]. Antioxidants (Basel),2021,10(6):890. doi: 10.3390/antiox10060890 [13] CHANDRA S, EHRLICH K C, LACEY M, et al. Epigenetics and expression of key genes associated with cardiac fibrosis: NLRP3, MMP2, MMP9, CCN2/CTGF and AGT[J]. Epigenomics,2021,13(3):219-234. doi: 10.2217/epi-2020-0446 [14] DONG F, ABHIJIT T, JIWON L, et al. Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease[J]. Fibrogenesis Tissue Repair, 2012, 15(5(1)). [15] 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. [16] 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. doi: 10.1002/ptr.5777 [17] FAN D, TAKAWALE A, LEE J, et al. Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease[J]. Fibrogenesis Tissue Repair,2012,5(1):15. doi: 10.1186/1755-1536-5-15 [18] MARCONI G D, FONTICOLI L, RAJAN T S, et al. Epithelial-mesenchymal transition (EMT): the type-2 EMT in wound healing, tissue regeneration and organ fibrosis[J]. Cells,2021,10(7):1587. doi: 10.3390/cells10071587 [19] KALLURI R, NEILSON E G. Epithelial-mesenchymal transition and its implications for fibrosis[J]. J Clin Invest,2003,112(12):1776-1784. doi: 10.1172/JCI200320530 [20] JIANG Y F, YOU F M, ZHU J, et al. Cryptotanshinone ameliorates radiation-induced lung injury in rats[J]. Evid Based Complement Alternat Med,2019,2019:1908416. [21] ROEHLEN N, CROUCHET E, BAUMERT T F. Liver fibrosis: mechanistic concepts and therapeutic perspectives[J]. Cells,2020,9(4):875. doi: 10.3390/cells9040875 [22] ALTAMIRANO-BARRERA A, BARRANCO-FRAGOSO B, MÉNDEZ-SÁNCHEZ N. Management strategies for liver fibrosis[J]. Ann Hepatol,2017,16(1):48-56. doi: 10.5604/16652681.1226814 [23] NAGAPPAN A, KIM J H, JUNG D Y, et al. Cryptotanshinone from the Salvia miltiorrhiza bunge attenuates ethanol-induced liver injury by activation of AMPK/SIRT1 and Nrf2 signaling pathways[J]. Int J Mol Sci,2019,21(1):265. doi: 10.3390/ijms21010265 [24] LAN H Y. Diverse roles of TGF-β/Smads in renal fibrosis and inflammation[J]. Int J Biol Sci,2011,7(7):1056-1067. doi: 10.7150/ijbs.7.1056 [25] 段红梅, 吴志远, 江黎明. 隐丹参酮对人皮肤瘢痕胶原基因表达的影响[J]. 齐齐哈尔医学院学报, 2009, 30(3):267. doi: 10.3969/j.issn.1002-1256.2009.03.006 [26] 杨莉, 李雪莉, 宋静卉, 等. 隐丹参酮抑制模型兔耳增生性瘢痕的作用及机制[J]. 中国组织工程研究, 2021, 25(20):3150-3155. doi: 10.3969/j.issn.2095-4344.3221 [27] LI Y, SHI S, GAO J X, et al. Cryptotanshinone downregulates the profibrotic activities of hypertrophic scar fibroblasts and accelerates wound healing: a potential therapy for the reduction of skin scarring[J]. Biomed Pharmacother,2016,80:80-86. doi: 10.1016/j.biopha.2016.03.006
计量
- 文章访问数: 4071
- HTML全文浏览量: 1962
- PDF下载量: 15
- 被引次数: 0