冰片对丹参脂溶性药效成分促吸收作用研究
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摘要
目的探讨冰片对丹参脂溶性药效成分二氢丹参酮Ⅰ、隐丹参酮、丹参酮Ⅰ和丹参酮ⅡA的促吸收作用,以及4种药效成分在大鼠血浆、脑和心脏组织中分布的影响。方法取SD大鼠20只,随机分为冰片组和未加冰片组,各10只,两组灌胃丹参醇提物后,冰片组立即灌胃冰片,测定给药30 min后4种药效成分的血药浓度,以及脑和心脏组织中的药物浓度。色谱柱采用Waters Symmetry C_(18)柱(250 mm×4. 6 mm,5μm),丙酸睾酮为内标,流动相为水-甲醇(22∶78),检测波长二氢丹参酮Ⅰ、丹参酮Ⅰ和丙酸睾酮为244 nm,隐丹参酮和丹参酮Ⅱ_A为266 nm。结果冰片组血浆样品可明显检测到隐丹参酮,而未加冰片组血浆样品中没有检测到隐丹参酮;冰片组心脏组织样品中隐丹参酮的峰高明显高于未加冰片组。两组的脑组织样品中均未检测到隐丹参酮,所有生物样品里均未检测到二氢丹参酮Ⅰ、丹参酮Ⅰ和丹参酮Ⅱ_A。结论丹参脂溶性药效成分的口服生物利用度很低,冰片能促进大鼠对隐丹参酮的吸收,能提高隐丹参酮在大鼠血液和心脏组织中的药物浓度。
Objective To investigate the absorption-promoting effect of borneol on the fat-soluble medicinal ingredients( such as dihydrotanshinone Ⅰ,cryptotanshinone,tanshinone Ⅰ and tanshinone Ⅱ_A) of Salvia miltiorrhiza,and to investigate the distribution of four medicinal ingredients in plasma,brain and heart of rats. Methods Totally 20 rats were randomly divided into borneol group and non-borneol group, and all the rats were given intragastric administration of ethanol extract of Salvia miltiorrhiza, then the rats in borneol group were given borneol immediately. After 30 min of administration,the concentration of four medicinal ingredients in blood,brain and heart tissues were detected, and the difference of drug concentration between the two groups was analyzed. Waters Symmetry C_(18) column( 250 mm × 4. 6 mm,5 μm) was used as the chromatographic column, testosterone propionate was used as the internal standard, the mobile phase was water-methanol( 22 ∶ 78), the detection wavelength of dihydrotanshinone Ⅰ, tanshinone Ⅰ and testosterone propionate was 244 nm, the detection wavelength of cryptotanshinone and tanshinone Ⅱ_A was 266 nm. Results Cryptotanshinone was detected in plasma samples of borneol group,but not in plasma samples of non-borneol group. The peak of cryptotanshinone in heart tissue samples of borneol group was higher than that of non-borneol group. Cryptotanshinone was not detected in brain tissue samples of the two groups,and dihydrotanshinone Ⅰ,tanshinone Ⅰ and tanshinone Ⅱ_A were not detected in all biological samples. Conclusion The oral bioavailability of fat-soluble medicinal ingredients of Salvia miltiorrhiza is very low. Borneol can promote the absorption of cryptotanshinone in rats and increase the concentration of cryptotanshinone in blood and heart tissues of rats.
Objective To investigate the absorption-promoting effect of borneol on the fat-soluble medicinal ingredients( such as dihydrotanshinone Ⅰ,cryptotanshinone,tanshinone Ⅰ and tanshinone Ⅱ_A) of Salvia miltiorrhiza,and to investigate the distribution of four medicinal ingredients in plasma,brain and heart of rats. Methods Totally 20 rats were randomly divided into borneol group and non-borneol group, and all the rats were given intragastric administration of ethanol extract of Salvia miltiorrhiza, then the rats in borneol group were given borneol immediately. After 30 min of administration,the concentration of four medicinal ingredients in blood,brain and heart tissues were detected, and the difference of drug concentration between the two groups was analyzed. Waters Symmetry C_(18) column( 250 mm × 4. 6 mm,5 μm) was used as the chromatographic column, testosterone propionate was used as the internal standard, the mobile phase was water-methanol( 22 ∶ 78), the detection wavelength of dihydrotanshinone Ⅰ, tanshinone Ⅰ and testosterone propionate was 244 nm, the detection wavelength of cryptotanshinone and tanshinone Ⅱ_A was 266 nm. Results Cryptotanshinone was detected in plasma samples of borneol group,but not in plasma samples of non-borneol group. The peak of cryptotanshinone in heart tissue samples of borneol group was higher than that of non-borneol group. Cryptotanshinone was not detected in brain tissue samples of the two groups,and dihydrotanshinone Ⅰ,tanshinone Ⅰ and tanshinone Ⅱ_A were not detected in all biological samples. Conclusion The oral bioavailability of fat-soluble medicinal ingredients of Salvia miltiorrhiza is very low. Borneol can promote the absorption of cryptotanshinone in rats and increase the concentration of cryptotanshinone in blood and heart tissues of rats.
引文
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[11]YANG S,ZHANG K,LIN X,et al.Pharmacokinetic comparisons of single herb extract of Fufang Danshen preparation with different combinations of its constituent herbs in rats[J].J Pharm Biomed Anal,2012,67-68:77-85.
[12]魏楚蓉,伍赶球.冰片的药理作用及其机制研究进展[J].国际病理科学与临床杂志,2010,30(4):447-451.
[13]周陆怡,鲁澄宇.丹参素在大鼠骨组织中分布动力学研究[J].中国骨质疏松杂志2010,16(7):483-486.
[14]周陆怡,鲁澄宇.丹参素在大鼠主要组织分布中的动力学特征[J].中国组织工程研究与临床康复,2010,14(37):6938-6942.
[15]高晓燕,杜晓鹃,赵春颖.补肾中药对成骨样细胞UMR106增殖的影响[J].承德医学院学报,2001,18(4):283-285.
[16]周陆怡,鲁澄宇.大鼠腹腔注射复方丹参注射液后血清中丹参素的测定[J].中药药理与临床,2013,29(4):113-115.
[2]ZHANG Y,AKAO T,NAKAMURA N,et al.Magnesium Lithospermate B is excreted rapidly into rat bile mostly as methylated metabolites,which are potent antioxidants[J].Drug Metab Dispos,2004,32(7):752-757.
[3]郭治昕,贾伟,高文远,等.复方丹参滴丸治疗冠心病心绞痛的临床研究[J].中国天然药物,2003,1(2):124-128.
[4]胡利民.冰片及配伍对血脑屏障通透性的影响和脑保护作用机制研究[D].天津:天津中医学院,2004.
[5]YU H,SUBEDI RK,NEPAL PR,et al.Enhancement of Solubility and Dissolution Rate of Cryptotanshinone,TanshinoneⅠand TanshinoneⅡA Extracted from Salvia miltiorrhiza[J].Arch Pharm Res,2012,35(8):1457-1464.
[6]YU XY,LIN SG,ZHOU ZW,et al.Role of P-glycoprotein in the intestinal absorption of tanshinoneⅡA,a major active ingredient in the root of Salvia Miltiorrhiza Bunge[J].Curr Drug Metab,2007,8(4):325-340.
[7]薛明,崔颖,汪汉卿,等.隐丹参酮及其代谢物在猪体内的药代动力学研究[J].药学学报,1999,34(2):81-84.
[8]BI HC,LAW FC,ZHONG GP,et al.Study of tanshinoneⅡAtissue distribution in rat by liquid chromatography-tandem mass spectrometry method[J].Biomed Chromatogr,2007,21(5):473-479.
[9]CHEN X,ZHOU ZW,XUE CC,et al.Role of P-glycoprotein in restricting the brain penetration of tanshinoneⅡA,a major active constituent from the root of Salvia miltiorrhiza Bunge,across the blood brain barrier[J].Xenobiotica,2007,37(6):635-678.
[10]HAO H,WANG G,CUI N,et al.Pharmacokineties,absorption and tissue distribution of tanshinoneⅡA solid dispersion[J].Planta Med,2006,72(14):1311-1317.
[11]YANG S,ZHANG K,LIN X,et al.Pharmacokinetic comparisons of single herb extract of Fufang Danshen preparation with different combinations of its constituent herbs in rats[J].J Pharm Biomed Anal,2012,67-68:77-85.
[12]魏楚蓉,伍赶球.冰片的药理作用及其机制研究进展[J].国际病理科学与临床杂志,2010,30(4):447-451.
[13]周陆怡,鲁澄宇.丹参素在大鼠骨组织中分布动力学研究[J].中国骨质疏松杂志2010,16(7):483-486.
[14]周陆怡,鲁澄宇.丹参素在大鼠主要组织分布中的动力学特征[J].中国组织工程研究与临床康复,2010,14(37):6938-6942.
[15]高晓燕,杜晓鹃,赵春颖.补肾中药对成骨样细胞UMR106增殖的影响[J].承德医学院学报,2001,18(4):283-285.
[16]周陆怡,鲁澄宇.大鼠腹腔注射复方丹参注射液后血清中丹参素的测定[J].中药药理与临床,2013,29(4):113-115.
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