冰片引经作用的探讨及其分子机制研究进展

赵洋洋; 郭玉洪; 黄汕梅; 银帮巧; 唐耀平

doi:10.14148/j.issn.1672-0482.2021.0150

冰片引经作用的探讨及其分子机制研究进展

doi: 10.14148/j.issn.1672-0482.2021.0150

赵洋洋^1,,
郭玉洪¹,
黄汕梅¹,
银帮巧¹,
唐耀平^{1, 2, ,}

1.
广西中医药大学科学实验中心, 广西南宁 530200
2.
广西中医药大学附属瑞康医院, 广西南宁 530011

基金项目:

国家自然科学基金 81774115

国家自然科学基金 81460721

广西中医药大学研究生教育创新计划项目 YCSZ2018011

详细信息

作者简介:
赵洋洋, 女, 硕士研究生, E-mail: wangyi2338@126.com

通讯作者:
唐耀平, 男, 教授, 主任医师, 博士生导师, 主要从事中西医结合心血管疾病防治研究, E-mail: typqc@126.com

中图分类号: R285
计量
- 文章访问数: 711
- HTML全文浏览量: 153
- PDF下载量: 1650
- 被引次数: 0
出版历程
- 收稿日期: 2020-03-28
- 网络出版日期: 2021-12-21
- 刊出日期: 2021-01-10
- 发布日期: 2021-01-15

Advances in Research on the Pharmacological Effects and Molecular Mechanisms of Borneol Guiding Action

1.
Science Experiment Center of Guangxi University of Chinese Medicine, Nanning, 530200, China
2.
Ruikang Hospital Affiliated to Guangxi University of Chinese medicine, Nanning, 530011, China

摘要

摘要: 冰片在传统医学中常作为一味佐使药, 在我国有着悠久的药用历史, 现代医学也证实其对心脑血管等诸多疾病具有良好的治疗作用。近年来, 国内外众多学者对冰片的药理作用及其机制进行了广泛研究, 通过对相关研究资料进行整理和分析, 发现冰片可促进药物通过血脑屏障、黏膜、胃肠道、皮肤等部位, 可能发挥了引经作用。其内在分子机制包括抑制转运蛋白外泵功能、调节生物化学物质水平、改变皮肤角质层的结构变化以及疏松内皮细胞紧密连接结构等。为了进一步探讨冰片具有类似引经作用的科学内涵, 以期为基于中药引经报使概念研究靶向给药系统的新思路提供理论参考, 现就相关研究进行综述。
- 冰片 /
- 引经 /
- 药理作用 /
- 分子机制
Abstract: Borneol is often used as an adjuvant in traditional Chinese medicine and has a long history of medicinal use. Modern medicine also proved that borneol has a good therapeutic effect on cardiovascular and cerebrovascular diseases. Many scholars at home and abroad had carried out extensive research on the pharmacological effect and mechanism of borneol adjuvant theory in recent years. Based on the analysis of the research data in recent years, it can be found that borneol also plays a guiding action in the compatibility of medicines. Borneol can promote the passage of drugs through the blood-brain barrier, the mucosa, the gastrointestinal tract and the skin by summarizes the discussion. The synergistic molecular mechanisms of borneol include inhibiting the function of transporter excretion, regulating the level of biochemical substances, changing the structure of the stratum corneum, and loosening the tight connective structure of endothelial cells. In order to further exploring the scientific connotation of borneol in guiding action, with a view to providing a theoretical reference for a new idea of targeted drug delivery system based on the concept of guiding action in traditional Chinese medicine, a review of related research is now conducted.
- borneol /
- medicinal guide /
- pharmacological effects /
- molecular mechanisms

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图 1 冰片引经药理作用及分子机制示意图

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参考文献(78)

[1]	雷载权. 中药学[M]. 上海: 上海科学技术出版社, 1995: 271.
[2]	李时珍. 本草纲目[M]. 胡双元, 校注. 太原: 山西科学技术出版社, 2014: 894.
[3]	寇宗奭. 本草衍义[M]. 北京: 中国医药科技出版社, 2012: 91.
[4]	苏坤莲, 凡永杰, 刘原, 等. 冰片对心脑血管系统药理作用及其机制的研究进展[J]. 辽宁中医杂志, 2018, 45(9): 2001-2003. https://www.cnki.com.cn/Article/CJFDTOTAL-LNZY201809067.htm
[5]	查英, 官玲亮, 白琳, 等. 天然冰片研究进展[J]. 热带农业科学, 2019, 39(3): 97-104. https://www.cnki.com.cn/Article/CJFDTOTAL-RDNK201903017.htm
[6]	尤在泾. 金匮要略心典[M]. 北京: 人民卫生出版社, 1987: 263.
[7]	吴鞠通. 医医病书[M]. 沈凤阁, 校注. 南京: 江苏科学技术出版社, 1985: 65.
[8]	YU B, RUAN M, DONG XP, et al. The mechanism of the opening of the blood-brain barrier by borneol: A pharmacodynamics and pharmacokinetics combination study[J]. J Ethnopharmacol, 2013, 150(3): 1096-1108. doi: 10.1016/j.jep.2013.10.028
[9]	BERTRAND L, CHO HJ, TOBOREK M. Blood-brain barrier pericytes as a target for HIV-1 infection[J]. Brain, 2019, 142(3): 502-511. doi: 10.1093/brain/awy339
[10]	杨乐, 吴军勇, 胡雄彬, 等. 冰片对葛根素透过体外模拟血脑屏障的影响[J]. 中草药, 2017, 48(16): 3408-3411. doi: 10.7501/j.issn.0253-2670.2017.16.025
[11]	DESTEFANO JG, JAMIESON JJ, LINVILLE RM, et al. Benchmarking in vitro tissue-engineered blood-brain barrier models[J]. Fluid Barr CNS, 2018, 15(1): 32. doi: 10.1186/s12987-018-0117-2
[12]	杨彩霞, 张秋菊, 徐名刷, 等. 冰片对血脑屏障通透性的影响及对药物的促透作用研究进展[J]. 甘肃中医药大学学报, 2018, 35(4): 96-99. https://www.cnki.com.cn/Article/CJFDTOTAL-GSZX201804027.htm
[13]	CHEN Y, LIU LH. Modern methods for delivery of drugs across the blood-brain barrier[J]. Adv Drug Deliv Rev, 2012, 64(7): 640-665. doi: 10.1016/j.addr.2011.11.010
[14]	SONG H, WEI M, ZHANG N, et al. Enhanced permeability of blood-brain barrier and targeting function of brain via borneol-modified chemically solid lipid nanoparticle[J]. Int J Nanomedicine, 2018, 13: 1869-1879. doi: 10.2147/IJN.S161237
[15]	ZHANG Q, WU D, WU J, et al. Improved blood-brain barrier distribution: effect of borneol on the brain pharmacokinetics of kaempferol in rats by in vivo microdialysis sampling[J]. J Ethnopharmacol, 2015, 162: 270-277. doi: 10.1016/j.jep.2015.01.003
[16]	FAN X, CHAI LJ, ZHANG H, et al. Borneol depresses P-glycoprotein function by a NF-κB signaling mediated mechanism in a blood brain barrier in vitro model[J]. Int J Mol Sci, 2015, 16(11): 27576-27588. doi: 10.3390/ijms161126051
[17]	YU B, RUAN M, DONG XP, et al. The mechanism of the opening of the blood-brain barrier by borneol: A pharmacodynamics and pharmacokinetics combination study[J]. J Ethnopharmacol, 2013, 150(3): 1096-1108. doi: 10.1016/j.jep.2013.10.028
[18]	张青, 李茂利, 赵阳, 等. 黄芪加冰片对大鼠脑缺血再灌注损伤后VEGF表达的影响[J]. 山东医药, 2010, 50(7): 88. doi: 10.3969/j.issn.1002-266X.2010.07.050
[19]	LYU Z, YANG YW, WANG J, et al. Optimization of the preparation conditions of borneol-modified ginkgolide liposomes by response surface methodology and study of their blood brain barrier permeability[J]. Molecules, 2018, 23(2): E303. doi: 10.3390/molecules23020303
[20]	DING JJ, SUN YJ, LI JF, et al. Enhanced blood-brain barrier transport of vinpocetine by oral delivery of mixed micelles in combination with a message guider[J]. J Drug Target, 2017, 25(6): 532-540. doi: 10.1080/1061186X.2017.1289541
[21]	YIN Y, CAO L, GE HF, et al. L-Borneol induces transient opening of the blood-brain barrier and enhances the therapeutic effect of cisplatin[J]. Neuroreport, 2017, 28(9): 506-513. doi: 10.1097/WNR.0000000000000792
[22]	王宁生, 梁美容. 冰片"佐使则有功"之实验研究[J]. 中医杂志, 1994, 35(1): 46-47. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ199401029.htm
[23]	WU JY, LI YJ, YANG L, et al. Borneol and α-asarone as adjuvant agents for improving blood-brain barrier permeability of puerarin and tetramethylpyrazine by activating adenosine receptors[J]. Drug Deliv, 2018, 25(1): 1858-1864. doi: 10.1080/10717544.2018.1516005
[24]	徐伟, 王宗锐. 薄荷醇及冰片对磺胺嘧啶和伊文思蓝在脑中分布的影响[J]. 中药药理与临床, 1995, 11(6): 31-33. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYYL506.010.htm
[25]	ZHANG XG, SONG Y, SHAN C, et al. Borneol attenuates ultrasound-targeted microbubble destruction-induced blood-brain barrier opening in focal cerebral ischemia[J]. Front Neurol, 2017, 8: 704. doi: 10.3389/fneur.2017.00704
[26]	段晓颖, 郝亚洁, 刘晓龙, 等. 黏膜给药系统药物吸收情况研究进展[J]. 中医学报, 2014, 29(3): 424-426. https://www.cnki.com.cn/Article/CJFDTOTAL-HNZK201403049.htm
[27]	JUG M, HAFNER A, LOVRIC J, et al. An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems[J]. J Pharm Biomed Anal, 2018, 147: 350-366. doi: 10.1016/j.jpba.2017.06.072
[28]	吴庆知, 高秋华, 朱玉山, 等. 冰片对胰岛素透黏膜吸收的促进作用研究[J]. 华中科技大学学报(自然科学版), 2001, 29(A01): 41-43. https://www.cnki.com.cn/Article/CJFDTOTAL-HZLG2001S1013.htm
[29]	LU Y, DU SY, CHEN XL, et al. Enhancing effect of natural borneol on the absorption of geniposide in rat via intranasal administration[J]. J Zhejiang Univ Sci B, 2011, 12(2): 143-148. doi: 10.1631/jzus.B1000121
[30]	陆洋, 杜守颖, 姚宗玲, 等. 天然冰片、合成冰片对栀子提取物黏膜促渗作用研究[J]. 中国中药杂志, 2009, 34(10): 1207-1210. doi: 10.3321/j.issn:1001-5302.2009.10.005
[31]	杨洪滨, 李志坚, 于楠楠, 等. 冰片对血眼屏障通透性的影响[J]. 国际眼科杂志, 2008, 8(8): 1576-1578. https://www.cnki.com.cn/Article/CJFDTOTAL-GJYK200808026.htm
[32]	LI ZJ, SUN DJ, YANG HB, et al. Effect of borneol on the distribution of danshensu to the eye in rabbit via oral administration[J]. Curr Eye Res, 2010, 35(7): 565-572. doi: 10.3109/02713681003718091
[33]	YANG H, XUN Y, LI Z, et al. Influence of borneol on in vitro corneal permeability and on in vivo and in vitro corneal toxicity[J]. J Int Med Res, 2009, 37(3): 791-802. doi: 10.1177/147323000903700322
[34]	杨洪滨, 寻延滨, 张小宇, 等. 局部应用天然与合成冰片的眼刺激性与长期毒性[J]. 国际眼科杂志, 2008, 8(11): 2228-2231. https://www.cnki.com.cn/Article/CJFDTOTAL-GJYK200811022.htm
[35]	QI HP, GAO XC, ZHANG LQ, et al. In vitro evaluation of enhancing effect of borneol on transcorneal permeation of compounds with different hydrophilicities and molecular sizes[J]. Eur J Pharmacol, 2013, 705(1/2/3): 20-25. http://www.sciencedirect.com/science?_ob=ShoppingCartURL&_method=add&_eid=1-s2.0-S0014299913001362&originContentFamily=serial&_origin=article&_ts=1433687340&md5=ed1879445a6dd87f61e5778a99c028d1
[36]	沈爱祥, 王继红, 丁洁瑾, 等. 珍珠明目滴眼液联合自体血清治疗角膜溃疡临床疗效分析[J]. 辽宁中医杂志, 2011, 38(7): 1361-1363. https://www.cnki.com.cn/Article/CJFDTOTAL-LNZY201107047.htm
[37]	吴丽娜, 李杨, 李英伦. 引经药与药物转运体的研究进展[J]. 中兽医学杂志, 2015(1): 67-72. doi: 10.3969/j.issn.1003-8655.2015.01.045
[38]	滕毅, 杨海玲. 冰片在药代动力学方面的研究进展[J]. 中国临床药理学与治疗学, 2015, 20(4): 469-475. https://www.cnki.com.cn/Article/CJFDTOTAL-YLZL201504026.htm
[39]	胡利民, 樊官伟, 高秀梅, 等. 天然冰片、合成冰片对大鼠胃黏膜屏障影响的比较[J]. 天津中医学院学报, 2005(3): 123-125. https://www.cnki.com.cn/Article/CJFDTOTAL-TZYY200503004.htm
[40]	胡慧玲, 王战国, 蒋学华, 等. 冰片对盐酸小檗碱在大鼠小肠吸收的影响[J]. 中国医院药学杂志, 2009, 29(4): 281-284. doi: 10.3321/j.issn:1001-5213.2009.04.009
[41]	邹亮, 林俊芝, 胡慧玲, 等. 冰片对麝香酮在大鼠小肠吸收的影响[J]. 中国中药杂志, 2012, 37(22): 3490-3493. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY201222033.htm
[42]	陈章强, 洪浪, 王洪, 等. 通心络对AMI延迟介入治疗术后血小板活化因子、血管内皮功能、TIMI血流分级的影响[J]. 中国中西医结合杂志, 2016, 36(4): 415-420. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXJ201604008.htm
[43]	肖衍宇, 陈志鹏, 平其能, 等. 冰片对川芎嗪促吸收作用的研究[J]. 药学学报, 2009, 44(8): 915-921. doi: 10.3321/j.issn:0513-4870.2009.08.016
[44]	HE HJ, SHEN Q, LI J. Effects of borneol on the intestinal transport and absorption of two P-glycoprotein substrates in rats[J]. Arch Pharm Res, 2011, 34(7): 1161-1170. doi: 10.1007/s12272-011-0714-y
[45]	PAUDEL KS, MILEWSKI M, SWADLEY CL, et al. Challenges and opportunities in dermal/transdermal delivery[J]. Ther Deliv, 2010, 1(1): 109-131. doi: 10.4155/tde.10.16
[46]	PRAUSNITZ MR. Microneedles for transdermal drug delivery[J]. Adv Drug Deliv Rev, 2004, 56(5): 581-587. doi: 10.1016/j.addr.2003.10.023
[47]	张泰. 芳香性中药成分透皮吸收促进作用的研究进展[J]. 中华中医药杂志, 2019, 34(6): 2589-2592. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201906069.htm
[48]	陆姗姗, 赵玉荣, 姚俊宏, 等. 中药挥发油透皮吸收促进剂制剂技术的研究进展[J]. 中草药, 2018, 49(10): 2477-2481. doi: 10.7501/j.issn.0253-2670.2018.10.033
[49]	陈军, 刘培, 蒋秋冬, 等. 中药挥发油作为透皮吸收促进剂的现状与展望[J]. 中草药, 2014, 45(24): 3651-3655. doi: 10.7501/j.issn.0253-2670.2014.24.026
[50]	陈寅生, 李丽. 心脉通贴剂中冰片的透皮吸收实验研究[J]. 河南大学学报(医学版), 2006, 25(1): 30-31. https://www.cnki.com.cn/Article/CJFDTOTAL-KFYZ200601009.htm
[51]	姜家书, 谢其亮, 李敦明, 等. 气相色谱法测定通络祛痛膏中樟脑、薄荷脑和冰片含量[J]. 中国药业, 2014, 23(7): 31-32. https://www.cnki.com.cn/Article/CJFDTOTAL-YYGZ201407014.htm
[52]	李海燕, 康建, 李彦超, 等. GC-MS法同时测定伤湿止痛膏中樟脑薄荷脑冰片水杨酸甲酯的含量[J]. 解放军药学学报, 2018, 34(6): 510-513. https://www.cnki.com.cn/Article/CJFDTOTAL-JFJN201806009.htm
[53]	刘翔, 孙飞. 气相法测定麝香壮骨膏中樟脑、薄荷脑、冰片、水杨酸甲酯含量[J]. 中成药, 2009, 31(2): 231-234. doi: 10.3969/j.issn.1001-1528.2009.02.020
[54]	蔡晓盛, 袁由军, 龚昌要, 等. 青鹏软膏外涂联合冰片外敷治疗胺碘酮所致静脉炎临床研究[J]. 新中医, 2020, 52(8): 119-121. https://www.cnki.com.cn/Article/CJFDTOTAL-REND202008039.htm
[55]	YI QF, YAN J, TANG SY, et al. Effect of borneol on the transdermal permeation of drugs with differing lipophilicity and molecular organization of stratum corneum lipids[J]. Drug Dev Ind Pharm, 2016, 42(7): 1086-1093. doi: 10.3109/03639045.2015.1107095
[56]	HU XG, CHENG N, ZHAO JH, et al. Percutaneous absorption and brain distribution facilitation of borneol on tetramethylpyrazine in a microemulsion-based transdermal therapeutic system[J]. Asian J Pharm Sci, 2019, 14(3): 305-312. doi: 10.1016/j.ajps.2018.06.003
[57]	张春凤, 战伟, 杨中林, 等. 双环单萜促透剂对川芎嗪透皮吸收的影响[J]. 药学学报, 2010, 45(11): 1452-1458. https://www.cnki.com.cn/Article/CJFDTOTAL-YXXB201011020.htm
[58]	孔雪云, 陈琦, 吴祥, 等. 中西药联用相互作用研究进展[J]. 南京中医药大学学报, 2018, 34(1): 5-11. https://www.cnki.com.cn/Article/CJFDTOTAL-NJZY201801004.htm
[59]	王玉璘, 王少峡, 郭虹, 等. 血脑屏障中P-糖蛋白的调节机制[J]. 中国药理学通报, 2011, 27(9): 1196-1200. doi: 10.3969/j.issn.1001-1978.2011.09.004
[60]	WANG SX, TAN N, MA CC, et al. Inhibitory effects of benzaldehyde, vanillin, muscone and borneol on P-glycoprotein in caco-2 cells and everted gut sac[J]. Pharmacology, 2018, 101(5/6): 269-277. http://europepmc.org/abstract/MED/29502118
[61]	WU Y, WANG SJ, SHANG L, et al. Effect of borneol as a penetration enhancer on brain targeting of nanoliposomes: Facilitate direct delivery to neurons[J]. Nanomedicine (Lond), 2018, 13(21): 2709-2727. doi: 10.2217/nnm-2018-0282
[62]	ZHENG Q, CHEN ZX, XU MB, et al. Borneol, a messenger agent, improves central nervous system drug delivery through enhancing blood-brain barrier permeability: A preclinical systematic review and meta-analysis[J]. Drug Deliv, 2018, 25(1): 1617-1633. doi: 10.1080/10717544.2018.1486471
[63]	李伟荣, 姚丽梅, 宓穗卿, 等. 冰片对大鼠下丘脑组胺、5-羟色胺含量的影响[J]. 中药材, 2004, 27(12): 937-939. doi: 10.3321/j.issn:1001-4454.2004.12.022
[64]	李伟荣, 姚丽梅, 宓稳卿, 等. 冰片开放血脑屏障作用与组胺和5-羟色胺的关系[J]. 中国临床康复, 2006(3): 167-169. https://www.cnki.com.cn/Article/CJFDTOTAL-XDKF200603062.htm
[65]	吴娟, 谢晋, 张群林, 等. 中药引经理论的现代研究进展和思路[J]. 中国中药杂志, 2016, 41(13): 2428-2434. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY201613010.htm
[66]	王刚, 曾南, 王建, 等. 合成冰片影响血脑屏障开放促槲皮素脑吸收的研究[J]. 中药药理与临床, 2012, 28(1): 65-68. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYYL201201021.htm
[67]	吴俊杰, 汪宏锦, 杨帅, 等. 冰片对梓醇及葛根素透过局灶性脑缺血模型大鼠血脑屏障作用的研究[J]. 中国中药杂志, 2016, 41(21): 3988-3995. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY201621017.htm
[68]	WILLIAMS AC, BARRY BW. Terpenes and the lipid-protein-partitioning theory of skin penetration enhancement[J]. Pharm Res, 1991, 8(1): 17-24. doi: 10.1023/A:1015813803205
[69]	CHEN J, JIANG QD, CHAI YP, et al. Natural terpenes as penetration enhancers for transdermal drug delivery[J]. Molecules, 2016, 21(12): E1709. doi: 10.3390/molecules21121709
[70]	傅大莉, 雍小兰, 刘德芳, 等. 冰片对HaCaT细胞膜流动性及膜电位的影响[J]. 中国中医药信息杂志, 2015, 22(4): 62-66. https://www.cnki.com.cn/Article/CJFDTOTAL-XXYY201504018.htm
[71]	WANG R, WU ZM, YANG SF, et al. A molecular interpretation on the different penetration enhancement effect of borneol and menthol towards 5-fluorouracil[J]. Int J Mol Sci, 2017, 18(12): E2747. doi: 10.3390/ijms18122747
[72]	ZHANG CF, ZHAN W, YANG ZL, et al. Impacts of bicyclo-monoterpene enhancers on transdermal delivery of ligustrazine[J]. Acta Pharm Sin, 2010, 45(11): 1452-1458. http://www.cabdirect.org/abstracts/20113009958.html
[73]	葛朝莉, 韩漫夫, 白润涛, 等. 冰片促进血脑屏障开放的超微结构研究[J]. 中西医结合心脑血管病杂志, 2008, 6(10): 1183-1185. doi: 10.3969/j.issn.1672-1349.2008.10.026
[74]	CHEN ZZ, LU Y, DU SY, et al. Influence of borneol and muscone on geniposide transport through MDCK and MDCK-MDR1 cells as blood-brain barrier in vitro model[J]. Int J Pharm, 2013, 456(1): 73-79. doi: 10.1016/j.ijpharm.2013.08.017
[75]	汪宏锦, 吴俊杰, 薛强, 等. 冰片对血脑屏障通透性的双向调节作用影响因素及机制探讨[J]. 中国中药杂志, 2017, 42(11): 2200-2207. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZY201711028.htm
[76]	JIN D, WANG F, QU LJ, et al. The distribution and expression of claudin-5 and occludin at the rat blood-optic nerve barrier after borneol treatment[J]. Mol Biol Rep, 2011, 38(2): 913-920. doi: 10.1007/s11033-010-0184-1
[77]	樊岚岚, 唐由之, 陆丽珠, 等. 冰片促秦皮甲素透过兔角膜上皮细胞实验研究[J]. 中国中药杂志, 2003, 28(1): 81-82. doi: 10.3321/j.issn:1001-5302.2003.01.028
[78]	CHEN ZZ, GONG X, LU Y, et al. Enhancing effect of borneol and muscone on geniposide transport across the human nasal epithelial cell monolayer[J]. PLoS ONE, 2014, 9(7): e101414. doi: 10.1371/journal.pone.0101414