芦荟大黄素抗肿瘤作用的药物传递系统研究进展
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摘要
肿瘤是多种因素诱发的细胞癌变,已经成为危害人类健康的重大疾病之一。芦荟大黄素是一种有着广泛药理作用的蒽醌类中药单体,有研究表明芦荟大黄素通过阻滞细胞周期、诱导肿瘤细胞凋亡、抗肿瘤细胞转移等作用机制发挥抗肿瘤作用。但芦荟大黄素的疏水性和在水溶液中固有的结晶倾向限制了其剂型开发和临床应用,适宜的药物传递系统能够促进中药有效成分的应用,提高其抗肿瘤疗效,降低不良反应。因此对芦荟大黄素在抗肿瘤作用方面的药物传递系统研究进展方面进行综述,为芦荟大黄素的剂型研究和临床应用提供新的思路和科研方向。
Tumor is a case of cell carcinogenesis induced by many factors,and it has become one of the major diseases endangering human's health. Aloe-emodin is a kind of anthraquinone monomers with extensive pharmacological effects. It has reported that aloe-emodin shows anti-tumor effects by inhibiting cell growth,arresting cell cycle,inducing tumor cell apoptosis and resisting tumor cell metastasis. However,due to the hydrophobicity of aloe-emodin and the aqueous solution crystallization tendency,the development and application of dosage forms of aloe-emodin are limited. An appropriate drug delivery system can promote the application of aloe-emodin,improve its anti-tumor effects and reduce adverse reactions. Therefore,drug delivery systems of aloe-emodin against tumor were reviewed,which can provide suggestions for the formulation research and clinical application of aloe-emodin.
Tumor is a case of cell carcinogenesis induced by many factors,and it has become one of the major diseases endangering human's health. Aloe-emodin is a kind of anthraquinone monomers with extensive pharmacological effects. It has reported that aloe-emodin shows anti-tumor effects by inhibiting cell growth,arresting cell cycle,inducing tumor cell apoptosis and resisting tumor cell metastasis. However,due to the hydrophobicity of aloe-emodin and the aqueous solution crystallization tendency,the development and application of dosage forms of aloe-emodin are limited. An appropriate drug delivery system can promote the application of aloe-emodin,improve its anti-tumor effects and reduce adverse reactions. Therefore,drug delivery systems of aloe-emodin against tumor were reviewed,which can provide suggestions for the formulation research and clinical application of aloe-emodin.
引文
1陈万青,郑荣寿,张思维.中国恶性肿瘤的动态变化[J].科技导报,2014,32(26):65-71
2 Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA-Cancer J Clin,2016,66(2):115-132
3 Zhou ZH,Yang J,Kong AN.Phytochemicals in Traditional Chinese Herbal Medicine:Cancer Prevention and Epigenetics Mechanisms[J].Current Pharmacology Reports,2017,3(2):77-91
4岳晨,王贤正,赵黎,等.长春碱类药物与中药复方联合运用治疗肺癌的进展[J].中国药师,2017,20(7):1229-1232
5 Min LW.Targeting apoptosis pathways in cancer by Chinese medicine[J].Cancer Lett,2013,332(2):304-312
6李牧,杜智敏.芦荟大黄素的药理作用研究进展[J].中国临床药理学杂志,2015,31(9):765-768
7 Yang M,Li L,Heo SM,et al.Aloe-Emodin Induces Chondrogenic Differentiation of ATDC5 Cells via MAP Kinases and BMP-2 Signaling Pathways[J].Biomol Ther,2016,24(4):395-401
8 Freag MS,Elnaggar YS,Abdelmonsif DA,et al.Stealth,biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells:in vitro and in vivo studies[J].Int J Nanomedicine,2016,11:4799-4818
9 Giuliani C,Altieri B,Bombelli C,et al.Remote Loading of Aloe Emodin in Gemini-Based Cationic Liposomes[J].Langmuir,2015,31(1):76-82
10乔赛男.中药大黄及其有效成分的荧光光谱研究[D].石家庄:河北师范大学博士学位论文,2013
11 Nadire,Mohamed S,LütfiyeD,et al.Aloe-emodin as drug candidate for cancer therapy[J].Oncotarget,2018,9(25):17770-17796
12 Chihara T,Shimpo K,Beppu H,et al.Effects of Aloe-emodin and Emodin on Proliferation of the MKN45 Human Gastric Cancer Cell Line[J].Asian Pac J Cancer P,2015,16(9):3887-3891
13 Chang X,Zhao J,Tian F,et al.Aloe-emodin suppresses esophageal cancer cell TE1 proliferation by inhibiting AKT and ERK phosphorylation[J].Oncol Lett,2016,12(3):2232-2238
14 Chang WT,You BJ,Yang WH,et al.Protein kinase C delta-mediated cytoskeleton remodeling is involved in aloe-emodin-induced photokilling of human lung cancer cells[J].Anticancer Res,2012,32(9):3707-3714
15 Trybus W,Krol T,Trybus E,et al.Induction of Mitotic Catastrophe in Human Cervical Cancer Cells After Administration of Aloe-emodin[J].Anticancer Res,2018,38(4):2037-2044
16 Liu K,Park C,Li S,et al.Aloe-emodin suppresses prostate cancer by targeting the m TOR complex 2[J].Carcinogenesis,2012,33(7):1406-1411
17 Tabolacci C,Lentini A,Mattioli P,et al.Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16-F10melanoma cells[J].Life Sci,2010,87(9):316-324
18 Cárdenas C,Quesada AR,Medina MA.Evaluation of the anti-angiogenic effect of aloe-emodin[J].Cell Mol Life Sci,2006,63(24):3083-3089
19 Dai W,Wang X,Song G,et al.Combination antitumor therapy with targeted dual-nanomedicines[J].Adv Drug Deliv Rev,2017,115:23-45
20 Wu YY,Zhang JH,Gao JH,et al.Aloe-emodin(AE)nanoparticles suppresses proliferation and induces apoptosis in human lung squamous carcinoma via ROS generation in vitro and in vivo[J].Biochem Bioph Res Co,2017,490(3):601-607
21 Chen R,Wang S,Zhang J,et al.Aloe-emodin loaded solid lipid nanoparticles:formulation design and in vitro anti-cancer study[J].Drug Deliv,2015,22(5):666-674
22陈玉林,桂双英,钱珊珊.溶致液晶作为药物载体的研究进展[J].中国新药杂志,2013,22(6):654-659
23 Chou TH,Liang CH.The molecular effects of aloe-emodin(AE)/liposome-AE on human nonmelanoma skin cancer cells and skin permeation[J].Chem Res Toxicol,2009,22(12):2017-2028
24曾嵘,周知午,吴翠芳,等.芦荟大黄素脂质体逆转人肺腺癌细胞A549/DDP对顺铂多药耐药的作用研究[J].中国中药杂志,2008,33(12):1443-1445
25 Liu D,He C,Wang AZ,et al.Application of liposomal technologies for delivery of platinum analogs in oncology[J].Int J Nanomed,2013,8:3309-3319
26 Li Z,Tan S,Li S,et al.Cancer drug delivery in the nano era:An overview and perspectives(Review)[J].Oncol Rep,2017,38(2):611-624
27 Josefsen LB,Boyle RW.Unique diagnostic and therapeutic roles of porphyrins and phthalocyanines in photodynamic therapy,imaging and theranostics[J].Theranostics,2012,2(9):916-966
28 Lee HZ,Yang WH,Hour MJ,et al.Photodynamic activity of aloeemodin induces resensitization of lung cancer cells to anoikis[J].Eur J Pharmacol,2010,648(1-3):50-58
29段勤勤,高青,李开庭,等.芦荟大黄素纳米脂质体介导的光动力对胃癌细胞的作用[J].重庆医科大学学报,2014,38(3):305-309
30王进荣,王平,杨永茂,等.单向灌流法评价芦荟大黄素大鼠体内肠吸收的研究[J].中国中药杂志,2011,36(17):2393-2398
31 Yu CP,Shia CS,Lin HJ,et al.Analysis of the pharmacokinetics and metabolism of aloe-emodin following intravenous and oral administrations in rats[J].Biomed Chromatogr,2016,30(10):1641-1647
32黄莹,廖迎,刘莉平,等.中药纳米凝胶透皮给药系统研究进展[J].大众科技,2017,19(12):49-50
33郭英,崔德生,汪子明.毛细管电泳法测定β-环糊精与芦荟大黄素包合反应平衡常数[J].应用化学,2009,26(4):492-494
2 Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA-Cancer J Clin,2016,66(2):115-132
3 Zhou ZH,Yang J,Kong AN.Phytochemicals in Traditional Chinese Herbal Medicine:Cancer Prevention and Epigenetics Mechanisms[J].Current Pharmacology Reports,2017,3(2):77-91
4岳晨,王贤正,赵黎,等.长春碱类药物与中药复方联合运用治疗肺癌的进展[J].中国药师,2017,20(7):1229-1232
5 Min LW.Targeting apoptosis pathways in cancer by Chinese medicine[J].Cancer Lett,2013,332(2):304-312
6李牧,杜智敏.芦荟大黄素的药理作用研究进展[J].中国临床药理学杂志,2015,31(9):765-768
7 Yang M,Li L,Heo SM,et al.Aloe-Emodin Induces Chondrogenic Differentiation of ATDC5 Cells via MAP Kinases and BMP-2 Signaling Pathways[J].Biomol Ther,2016,24(4):395-401
8 Freag MS,Elnaggar YS,Abdelmonsif DA,et al.Stealth,biocompatible monoolein-based lyotropic liquid crystalline nanoparticles for enhanced aloe-emodin delivery to breast cancer cells:in vitro and in vivo studies[J].Int J Nanomedicine,2016,11:4799-4818
9 Giuliani C,Altieri B,Bombelli C,et al.Remote Loading of Aloe Emodin in Gemini-Based Cationic Liposomes[J].Langmuir,2015,31(1):76-82
10乔赛男.中药大黄及其有效成分的荧光光谱研究[D].石家庄:河北师范大学博士学位论文,2013
11 Nadire,Mohamed S,LütfiyeD,et al.Aloe-emodin as drug candidate for cancer therapy[J].Oncotarget,2018,9(25):17770-17796
12 Chihara T,Shimpo K,Beppu H,et al.Effects of Aloe-emodin and Emodin on Proliferation of the MKN45 Human Gastric Cancer Cell Line[J].Asian Pac J Cancer P,2015,16(9):3887-3891
13 Chang X,Zhao J,Tian F,et al.Aloe-emodin suppresses esophageal cancer cell TE1 proliferation by inhibiting AKT and ERK phosphorylation[J].Oncol Lett,2016,12(3):2232-2238
14 Chang WT,You BJ,Yang WH,et al.Protein kinase C delta-mediated cytoskeleton remodeling is involved in aloe-emodin-induced photokilling of human lung cancer cells[J].Anticancer Res,2012,32(9):3707-3714
15 Trybus W,Krol T,Trybus E,et al.Induction of Mitotic Catastrophe in Human Cervical Cancer Cells After Administration of Aloe-emodin[J].Anticancer Res,2018,38(4):2037-2044
16 Liu K,Park C,Li S,et al.Aloe-emodin suppresses prostate cancer by targeting the m TOR complex 2[J].Carcinogenesis,2012,33(7):1406-1411
17 Tabolacci C,Lentini A,Mattioli P,et al.Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16-F10melanoma cells[J].Life Sci,2010,87(9):316-324
18 Cárdenas C,Quesada AR,Medina MA.Evaluation of the anti-angiogenic effect of aloe-emodin[J].Cell Mol Life Sci,2006,63(24):3083-3089
19 Dai W,Wang X,Song G,et al.Combination antitumor therapy with targeted dual-nanomedicines[J].Adv Drug Deliv Rev,2017,115:23-45
20 Wu YY,Zhang JH,Gao JH,et al.Aloe-emodin(AE)nanoparticles suppresses proliferation and induces apoptosis in human lung squamous carcinoma via ROS generation in vitro and in vivo[J].Biochem Bioph Res Co,2017,490(3):601-607
21 Chen R,Wang S,Zhang J,et al.Aloe-emodin loaded solid lipid nanoparticles:formulation design and in vitro anti-cancer study[J].Drug Deliv,2015,22(5):666-674
22陈玉林,桂双英,钱珊珊.溶致液晶作为药物载体的研究进展[J].中国新药杂志,2013,22(6):654-659
23 Chou TH,Liang CH.The molecular effects of aloe-emodin(AE)/liposome-AE on human nonmelanoma skin cancer cells and skin permeation[J].Chem Res Toxicol,2009,22(12):2017-2028
24曾嵘,周知午,吴翠芳,等.芦荟大黄素脂质体逆转人肺腺癌细胞A549/DDP对顺铂多药耐药的作用研究[J].中国中药杂志,2008,33(12):1443-1445
25 Liu D,He C,Wang AZ,et al.Application of liposomal technologies for delivery of platinum analogs in oncology[J].Int J Nanomed,2013,8:3309-3319
26 Li Z,Tan S,Li S,et al.Cancer drug delivery in the nano era:An overview and perspectives(Review)[J].Oncol Rep,2017,38(2):611-624
27 Josefsen LB,Boyle RW.Unique diagnostic and therapeutic roles of porphyrins and phthalocyanines in photodynamic therapy,imaging and theranostics[J].Theranostics,2012,2(9):916-966
28 Lee HZ,Yang WH,Hour MJ,et al.Photodynamic activity of aloeemodin induces resensitization of lung cancer cells to anoikis[J].Eur J Pharmacol,2010,648(1-3):50-58
29段勤勤,高青,李开庭,等.芦荟大黄素纳米脂质体介导的光动力对胃癌细胞的作用[J].重庆医科大学学报,2014,38(3):305-309
30王进荣,王平,杨永茂,等.单向灌流法评价芦荟大黄素大鼠体内肠吸收的研究[J].中国中药杂志,2011,36(17):2393-2398
31 Yu CP,Shia CS,Lin HJ,et al.Analysis of the pharmacokinetics and metabolism of aloe-emodin following intravenous and oral administrations in rats[J].Biomed Chromatogr,2016,30(10):1641-1647
32黄莹,廖迎,刘莉平,等.中药纳米凝胶透皮给药系统研究进展[J].大众科技,2017,19(12):49-50
33郭英,崔德生,汪子明.毛细管电泳法测定β-环糊精与芦荟大黄素包合反应平衡常数[J].应用化学,2009,26(4):492-494