隐丹参酮药理作用及其新型制剂技术的研究进展

doi:10.7501/j.issn.0253-2670.2024.14.028

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首页 > 过刊浏览>2024年第55卷第14期 >2024,55(14):4930-4938. DOI:10.7501/j.issn.0253-2670.2024.14.028

隐丹参酮药理作用及其新型制剂技术的研究进展

李佳莉
李佳莉
山东中医药大学药学院, 山东济南 250355;海军军医大学药学院, 上海 200433
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张利
张利
山东中医药大学药学院, 山东济南 250355;海军军医大学药学院, 上海 200433
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辛佳芸
辛佳芸
山东中医药大学药学院, 山东济南 250355;海军军医大学药学院, 上海 200433
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高苑
高苑
山东中医药大学药学院, 山东济南 250355;海军军医大学药学院, 上海 200433
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侯泉杰
侯泉杰
山东中医药大学药学院, 山东济南 250355
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徐希科
徐希科
海军军医大学药学院, 上海 200433
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冯玉
冯玉
山东中医药大学药学院, 山东济南 250355
通讯作者.
Email: fyshandong@163.com
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祖先鹏
祖先鹏
海军军医大学药学院, 上海 200433
通讯作者.
Email: zuxianpeng@163.com
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Research progress on pharmacological effects of cryptotanshinone and its novel preparation technology

LI Jiali
LI Jiali
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;School of Pharmacy, Naval Medical University, Shanghai 200433, China
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ZHANG Li
ZHANG Li
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;School of Pharmacy, Naval Medical University, Shanghai 200433, China
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XIN Jiayun
XIN Jiayun
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;School of Pharmacy, Naval Medical University, Shanghai 200433, China
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GAO Yuan
GAO Yuan
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;School of Pharmacy, Naval Medical University, Shanghai 200433, China
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HOU Quanjie
HOU Quanjie
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
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XU Xike
XU Xike
School of Pharmacy, Naval Medical University, Shanghai 200433, China
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FENG Yu
FENG Yu
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
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Email: fyshandong@163.com
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ZU Xianpeng
ZU Xianpeng
School of Pharmacy, Naval Medical University, Shanghai 200433, China
Contact Author.
Email: zuxianpeng@163.com
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发布日期：2024-07-19

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[关键词]

隐丹参酮 ; 抗肿瘤 ; 自噬 ; 新型制剂技术 ; 纳米粒 ; 水凝胶

[摘要]

隐丹参酮是从丹参Salvia miltiorrhiza中分离得到的具有抗肿瘤、神经保护、抗菌、抗炎等生物活性的脂溶性化学成分，但由于其难溶于水、口服生物利用度低等缺点，限制了其药效发挥及临床应用。采用新型制剂技术可以有效改善隐丹参酮的溶解度和生物利用度，并且还可以增强药物稳定性、实现靶向应答及缓控释药物的效果，具有良好的应用前景。通过对隐丹参酮的药理作用及新型制剂技术进行综述，为隐丹参酮的临床应用和新药研发提供研究依据。

[Key word]

cryptotanshinone ; antitumor ; autophagy ; novel preparation technology ; nanoparticles ; hydrogels

[Abstract]

Cryptotanshinone (CTS), a lipophilic chemical compound isolated from Danshen (Salvia miltiorrhiza), exhibits biological activities such as antitumor, neuroprotection, antibacterial, and anti-inflammatory properties. However, its poor solubility in water and low oral bioavailability hinder its efficacy and clinical application. The use of novel preparation technologies can effectively enhance the solubility and bioavailability of CTS, and also improve drug stability, enable targeted responses, and achieve controlled drug release, presenting promising application prospects. A review of the pharmacological effects of CTS and the novel preparation technologies provides a research basis for the clinical application of CTS and the development of new drugs.

[中图分类号]

R283;R285

[基金项目]

上海市卫生健康委员会中医药科研项目（2024QN057）;国家重点研发计划（2022YFC3502000）;军队后勤科研项目（BHJ22J020）;海军军医大学“深蓝”工程启航人才计划基金

引用本文 / Get Citation

李佳莉,张利,辛佳芸,高苑,侯泉杰,徐希科,冯玉,祖先鹏.隐丹参酮药理作用及其新型制剂技术的研究进展[J].中草药,2024,55(14):4930-4938

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历史 / History

收稿日期: 2024-02-06

在线发布日期: 2024-07-19

[1] 左婷.隐丹参酮皮肤角质类脂体给药系统的设计与评价[D].广州:南方医科大学, 2015.

[2] 薛明,史彦斌,周宗田,等.鼠尾草二萜醌及其衍生物的抗菌构效关系研究[J].中国农业科学, 2000, 33(3):88-93.

[3] Zhang J, Huang M, Guan S, et al. A mechanistic study of the intestinal absorption of cryptotanshinone, the major active constituent of Salvia miltiorrhiza[J]. J Pharmacol Exp Ther, 2006, 317(3):1285-1294.

[4] 曹毛毛,陈万青. GLOBOCAN 2020全球癌症统计数据解读[J].中国医学前沿杂志:电子版, 2021, 13(3):63-69.

[5] Liu C, Sun H N, Luo Y H, et al. Cryptotanshinone induces ROS-mediated apoptosis in human gastric cancer cells[J]. Oncotarget, 2017, 8(70):115398-115412.

[6] 马丽娟,王锡恩,刘培,等.隐丹参酮调控Wnt/β-catenin信号通路对胃癌细胞抑制作用的研究[J].新中医, 2020, 52(21):1-5.

[7] Dutchak P A, Estill-Terpack S J, Plec A A, et al. Loss of a negative regulator of mTORC1 induces aerobic glycolysis and altered fiber composition in skeletal muscle[J]. Cell Rep, 2018, 23(7):1907-1914.

[8] 马丽娟,王锡恩,张武广,等.隐丹参酮通过miR-124靶向调控PKM2基因表达抑制胃癌细胞的增殖和转移[J].中药材, 2020, 43(8):1976-1979.

[9] 弓建华,陈春雷.隐丹参酮抗肿瘤作用的研究进展[J].广东医学院学报, 2012, 30(1):87-90.

[10] 王加茹,徐宛婷,刘畅,等.隐丹参酮抗肿瘤药理作用机制研究进展[J].药物评价研究, 2018, 41(6):1160-1163.

[11] 张佳,李明花,袁星,等.隐丹参酮抗肿瘤作用机制的研究进展[J].中医研究, 2020, 33(7):76-80.

[12] Jung J H, Kwon T R, Jeong S J, et al. Apoptosis induced by tanshinone IIA and cryptotanshinone is mediated by distinct JAK/STAT3/5 and SHP1/2 signaling in chronic myeloid leukemia K562 cells[J]. Evid Based Complement Alternat Med, 2013, 2013:805639.

[13] 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.

[14] Park I J, Yang W K, Nam S H, et al. Cryptotanshinone induces G₁ cell cycle arrest and autophagic cell death by activating the AMP-activated protein kinase signal pathway in HepG2 hepatoma[J]. Apoptosis, 2014, 19(4):615-628.

[15] 叶因涛,王晨,宋晓坤,等.隐丹参酮对肝癌H₂₂荷瘤小鼠放射增敏作用的影响[J].中国癌症杂志, 2014, 24(1):29-34.

[16] 刘金丽,佟雷,宋懿玲,等.隐丹参酮对人肝癌HepG2细胞自噬及PI3K/Akt/mTOR信号通路的影响[J].现代预防医学, 2021, 48(13):2431-2435.

[17] 刘金丽,佟雷,罗烨,等.隐丹参酮可能具有诱导人肝癌HepG2细胞铁死亡的作用[J].中国医学科学院学报, 2021, 43(3):366-370.

[18] Dong B W, Liang Z R, Chen Z R, et al. Cryptotanshinone suppresses key onco-proliferative and drug-resistant pathways of chronic myeloid leukemia by targeting STAT5 and STAT3 phosphorylation[J]. Sci China Life Sci, 2018, 61(9):999-1009.

[19] Xu D F, Lin T H, Li S S, et al. Cryptotanshinone suppresses androgen receptor-mediated growth in androgen dependent and castration resistant prostate cancer cells[J]. Cancer Lett, 2012, 316(1):11-22.

[20] Wu C Y, Hsieh C Y, Huang K E, et al. Cryptotanshinone down-regulates androgen receptor signaling by modulating lysine-specific demethylase 1 function[J]. Int J Cancer, 2012, 131(6):1423-1434.

[21] Liu X M, Fang Y, Guo Q Q, et al. Cryptotanshinone induces apoptosis and autophagic cell death in prostate cancer cells[J]. Med One, 2017, 2:e170019.

[22] 尧义,李惠长,钱本江,等.隐丹参酮对前列腺癌DU145细胞中异黏蛋白表达的影响[J].中华男科学杂志, 2015, 21(9):782-787.

[23] 牛俊豪,张君.隐丹参酮调节TGF-β1/Smad3介导的上皮间质转化对抑制前列腺癌小鼠肿瘤生长的影响[J].实用癌症杂志, 2023, 38(4):529-533.

[24] Larsson O, Li S N, Issaenko O A, et al. Eukaryotic translation initiation factor 4E induced progression of primary human mammary epithelial cells along the cancer pathway is associated with targeted translational deregulation of oncogenic drivers and inhibitors[J]. Cancer Res, 2007, 67(14):6814-6824.

[25] Ge Y Q, Cheng R B, Zhou Y H, et al. Cryptotanshinone induces cell cycle arrest and apoptosis of multidrug resistant human chronic myeloid leukemia cells by inhibiting the activity of eukaryotic initiation factor 4E[J]. Mol Cell Biochem, 2012, 368(1/2):17-25.

[26] Cheng R B, Huang Y L, Fang Y, et al. Cryptotanshinone enhances the efficacy of Bcr-Abl tyrosine kinase inhibitors via inhibiting STAT3 and eIF4E signalling pathways in chronic myeloid leukaemia[J]. Pharm Biol, 2021, 59(1):893-903.

[27] Ni W M, Qian W B, Tong X M. Cryptotanshinone induces apoptosis of HL-60 cells via mitochondrial pathway[J]. Trop J Pharm Res, 2014, 13(4):545.

[28] 石丹宁,崔丽霞,赵丕文,等.基于GPER介导途径探讨隐丹参酮诱导人乳腺癌SKBR-3细胞凋亡的分子机制[J].中国中药杂志, 2019, 44(22):4905-4911.

[29] Shi D N, Li H B, Zhang Z Y, et al. Cryptotanshinone inhibits proliferation and induces apoptosis of breast cancer MCF-7 cells via GPER mediated PI3K/Akt signaling pathway[J]. PLoS One, 2022, 17(1):e0262389.

[30] 马楠,齐宝文,徐蓉. MiR-221-3p靶向沉默PARP1对三阴乳腺癌细胞的化疗药物敏感性的影响[J].广东医学, 2023, 44(8):925-933.

[31] 宋晓璐,乐翊飞,卢德赵.隐丹参酮通过调节SIRT3/HIF-1α信号轴和线粒体自噬抑制MDA-MB-231细胞增殖迁移的研究[J].中药材, 2020, 43(1):193-196.

[32] Ji Y B, Liu Y C, Xue N N, et al. Cryptotanshinone inhibits esophageal squamous-cell carcinoma in vitro and in vivo through the suppression of STAT3 activation[J]. Onco Targets Ther, 2019, 12:883-896.

[33] 王加茹,徐宛婷,朴仙姬,等.隐丹参酮诱导人食管癌HCE-4细胞凋亡的机制[J].肿瘤防治研究, 2018, 45(8):533-539.

[34] Man Y H, Yang L, Zhang D X, et al. Cryptotanshinone inhibits lung tumor growth by increasing CD4⁺ T cell cytotoxicity through activation of the JAK2/STAT4 pathway[J]. Oncol Lett, 2016, 12(5):4094-4098.

[35] Li X P, Li W, Yang P, et al. Anticancer effects of cryptotanshinone against lung cancer cells through ferroptosis[J]. Arab J Chem, 2021, 14(6):103177.

[36] Hao W H, Zhang X N, Zhao W W, et al. Cryptotanshinone induces pro-death autophagy through JNK signaling mediated by reactive oxygen species generation in lung cancer cells[J]. Anticancer Agents Med Chem, 2016, 16(5):593-600.

[37] Li W D, Saud S M, Young M R, et al. Cryptotanshinone, a STAT3 inhibitor, suppresses colorectal cancer proliferation and growth in vitro[J]. Mol Cell Biochem, 2015, 406(1/2):63-73.

[38] Wang H, Liu Z, Guan L N, et al. LYW-6, a novel cryptotanshinone derived STAT3 targeting inhibitor, suppresses colorectal cancer growth and metastasis[J]. Pharmacol Res, 2020, 153:104661.

[39] 黄岩,王洁,常文军,等. STAT3磷酸化抑制剂隐丹参酮提高5-FU诱导的结直肠癌细胞凋亡[J].国际药学研究杂志, 2016, 43(2):296-300.

[40] Fu X J, Zhao W W, Li K K, et al. Cryptotanshinone inhibits the growth of HCT116 colorectal cancer cells through endoplasmic reticulum stress-mediated autophagy[J]. Front Pharmacol, 2021, 12:653232.

[41] Xu Z Y, Jiang H, Zhu Y H, et al. Cryptotanshinone induces ROS-dependent autophagy in multidrug-resistant colon cancer cells[J]. Chem Biol Interact, 2017, 273:48-55.

[42] 刘莉,王雪梅,韩宇博,等.抗阿尔茨海默病的中药治疗及其作用机制研究概况[J].时珍国医国药, 2022, 33(10):2477-2480.

[43] Cui W B, Zhang Z P, Bai X, et al. Cryptotanshinone alleviates oxidative stress and reduces the level of abnormally aggregated protein in Caenorhabditis elegans AD models[J]. Int J Mol Sci, 2022, 23(17):10030.

[44] Mei Z R, Zhang F Y, Tao L, et al. Cryptotanshinone, a compound from Salvia miltiorrhiza modulates amyloid precursor protein metabolism and attenuates beta-amyloid deposition through upregulating alpha-secretase in vivo and in vitro[J]. Neurosci Lett, 2009, 452(2):90-95.

[45] Song M, Hang T J, Zhang Z H X, et al. Determination of cryptotanshinone and its metabolite in rat plasma by liquid chromatography-tandem mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2005, 827(2):205-209.

[46] 陈曦,赵永芳.丹参酮II_A对异丙肾上腺素致心肌缺血损伤大鼠apelin及其受体的影响[J].中国药物应用与监测, 2012, 9(1):18-21.

[47] 何晓静,王守涛,周娟,等.丹参酮II_A注射乳剂对脑缺血的保护作用[J].山西医药杂志, 2008, 37(6):517-519.

[48] 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.

[49] Li X X, Zheng X T, Liu Z J, et al. Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway[J]. Chin Med, 2020, 15:20.

[50] Lee D S, Lee S H, Noh J G, et al. Antibacterial activities of cryptotanshinone and dihydrotanshinone I from a medicinal herb, Salvia miltiorrhiza Bunge[J]. Biosci Biotechnol Biochem, 1999, 63(12):2236-2239.

[51] Chen B C, Ding Z S, Dai J S, et al. New insights into the antibacterial mechanism of cryptotanshinone, a representative diterpenoid quinone from Salvia miltiorrhiza bunge[J]. Front Microbiol, 2021, 12:647289.

[52] 范容晖,阳志强,李勃深,等.中药纳米技术靶向治疗脑部疾病研究进展[J].中国比较医学杂志, 2023, 33(6):128-140.

[53] 周珠贤,申有青,赵宇亮.抗肿瘤纳米药物递送系统的研究现状与展望[J].中国基础科学, 2022, 24(1):25-36.

[54] 彭国文,柳超,時晓静,等.隐丹参酮固体脂质纳米粒的制备及药动学研究[J].中药材, 2019, 42(3):626-629.

[55] Nie X L, Liu Y, Li M, et al. SP94 peptide-functionalized PEG-PLGA nanoparticle loading with cryptotanshinone for targeting therapy of hepatocellular carcinoma[J]. AAPS PharmSciTech, 2020, 21(4):124.

[56] Liu Y, Xie X M, Hou X F, et al. Functional oral nanoparticles for delivering silibinin and cryptotanshinone against breast cancer lung metastasis[J]. J Nanobiotechnology, 2020, 18(1):83.

[57] 刘娱姗,高署,柯学,等.难溶性药物固体分散体研究新进展[J].药学进展, 2013, 37(4):166-173.

[58] 罗昕,徐月红,陈宝,等.隐丹参酮固体分散体的制备及性质研究[J].中草药, 2005, 36(6):839-842.

[59] 周婷婷,曹玲,张宏喜.纤维素基水凝胶的研究进展[J].广东化工, 2020, 47(18):88-89.

[60] 崔航,王思琪,郭世好,等.水凝胶的制备及应用进展[J].化工新型材料, 2021, 49(S1):47-51.

[61] Yin Y J, Wu C, Wang J L, et al. A simply triggered peptide-based hydrogel as an injectable nanocarrier of tanshinone II_A and tanshinones[J]. Chem Commun, 2017, 53(3):529-532.

[62] Shu C, Li T F, Li D, et al. Anticancer activity and pharmacokinetics of tanshinone II_A derivative supramolecular hydrogels[J]. J Drug Deliv Sci Technol, 2018, 48:509-515.

[63] 黄健榕,杨凤,仲雨叶,等.环糊精包合物的研究进展[J].广东化工, 2015, 42(19):87-88.

[64] 谷福根,高永良,崔福德.环糊精包合物研究进展[J].中国新药杂志, 2005, 14(6):686-693.

[65] 许文才,黄少云,李东立,等.基于环糊精包合技术的活性包装研究进展[J].包装工程, 2010, 31(9):122-125.

[66] 张冕,万芳,王勇,等.隐丹参酮及其羟丙基-β-环糊精包合物在大鼠体内的药动学研究[J].荆楚理工学院学报, 2020, 35(2):42-46.

[67] 罗昕,徐月红,陈宝,等.羟丙基-β-环糊精对隐丹参酮的增溶作用及其包合物的制备[J].中国中药杂志, 2005, 30(17):1328-1331.

[68] 张晓伟.冷冻干燥法制备隐丹参酮纳米脂质体[J].忻州师范学院学报, 2008, 24(5):1-3.

[69] Ding Z Y, Xiao J J, Zhang Y, et al. Pharmacokinetics and liver uptake of three Schisandra lignans in rats after oral administration of liposome encapsulating β-cyclodextrin inclusion compound of Schisandra extract[J]. J Liposome Res, 2019, 29(2):121-132.

[70] van Broekhoven C L, Parish C R, Demangel C, et al. Targeting dendritic cells with antigen-containing liposomes:A highly effective procedure for induction of antitumor immunity and for tumor immunotherapy[J]. Cancer Res, 2004, 64(12):4357-4365.

[71] 杨光,陈晓青,陈中强.中药活性成分纳米系统在抗肿瘤中的应用研究[J].江汉大学学报:自然科学版, 2020, 48(2):33-40.

[72] 黎绫,龙爱平,王碧霞,等.微乳给药系统的研究与应用进展[J].湘南学院学报:医学版, 2020, 22(3):69-71.

[73] 林跃虹,杨惊宇,刘西京,等.隐丹参酮微乳的制备与质量评价[J].新中医, 2009, 41(5):100-102.

[74] 刘筱雅,江昌照,高文彦,等.微乳和基于微乳的经皮给药制剂的研究进展[J].中国医药工业杂志, 2020, 51(4):442-449.

[75] Li H Y, Gao C D, Liu C, et al. A review of the biological activity and pharmacology of cryptotanshinone, an important active constituent in Danshen[J]. Biomedecine Pharmacother, 2021, 137:111332.

[76] 曾华婷,郭健,陈彦.淫羊藿素药理作用及其新型给药系统的研究进展[J].中草药, 2020, 51(20):5372-5380.