Similar articles

Abstract: Objective: This study was designed to investigate the pharmacokinetics of borneol in the pathological conditions of stroke and evaluate the pharmacokinetic differences of borneol caused by stroke after oral administration of borneol and xingnaojing (XNJ). Methods: The rats were divided into two groups, ischemia-reperfusion (IR) and sham-operated (SO) rats. Each group contained two subgroups: pure borneol and XNJ subgroups. After administration with the same dosages of borneol 162.0 mg/kg, plasma samples were collected. The cerebral ischemia-reperfusion model was created by reversible middle cerebral artery occlusion (MCAO). The blood samples were collected punctually after oral administration and a specific gas chromatographic system-flame ionization detector (GC-FID) method was developed and employed to determine the level of borneol in the plasma. The pharmacokinetic parameters were analyzed using non-compartmental methods with Kinetica. Results: After administration of borneol, the maximum plasma concentration (C _max) and area under the curve (AUC) values in stroke rats significantly increased by 302% and 275%, respectively, compared with the SO rats, and the same phenomenon appeared after administration of XNJ. In the rats with the same physiological conditions, the C _max and AUC had higher values in the borneol subgroup (P<0.05). Conclusions: These results suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of borneol and that there are some components in XNJ inhibiting the absorption of borneol.

冰片在中风及假手术大鼠体内的药代动力学研究

研究目的：中风的发生对冰片药代动力学特征的影响。
创新方法：首次对冰片及其中药制剂在脑取血再灌注（中风病理状态下）的药代动力学进行研究，为药物在中风治疗中的应用提供参考。
研究手段：采用大脑中动脉堵塞法建立脑缺血中风模型，中风组和假手术组分别灌胃冰片与醒脑静口服制剂，不同时间点眼眶取血后用气相色谱氢火焰离子化检测器（GC-FID）测定，并用非房室模型分析药时曲线（见图3），得各药代动力学参数（见表2）。
重要结论：脑取血再灌注损伤（中风状态）可以促进冰片的吸收及生物利用，醒脑静中其他成分对其药代动力学特征也有一定影响。

关键词：冰片；药代动力学；脑缺血再灌注；醒脑静

[1] Cai, D.F., Zhao, J.H., Ruan, Q.M., 2000. Clinical and experimental study on Xingnaojing injection in treating acute ischemic cerebral apoplexy. J Emerg Tradit Chin Med, (in Chinese),9(2):45-47. 

[2] Cai, Z., Hou, S., Li, Y., 2008. Effect of borneol on the distribution of gastrodin to the brain in mice via oral administration. J Drug Target, 16(2):178-184. 

[3] Dai, J.P., Chen, J., Bei, Y.F., 2009. Influence of borneol on primary mice oral fibroblasts: a penetration enhancer may be used in oral submucous fibrosis. J Oral Pathol Med, 38(3):276-281. 

[4] Ehrnhfer-Ressler, M.M., Fricke, K., Pignitter, M., 2013. Identification of 1,8-cineole, borneol, camphor, and thujone as anti-inflammatory compounds in a Salvia officinalis L. infusion using human gingival fibroblasts. J Agric Food Chem, 61(14):3451-3459. 

[5] Georgilis, K., Plomaritoglou, A., Dafni, U., 1999. Aetiology of fever in patients with acute stroke. J Intern Med, 246(2):203-209. 

[6] Goldstein, M., Barnett, H.J.M., Orgogozo, J.M., 1989. Stroke-1989: recommendations on stroke prevention, diagnosis, and therapy. Report of the WHO Task Force on Stroke and Other Cerebrovascular Disorders. Stroke, 20(10):1407-1431. 

[7] Guo, F., Lu, X.W., Xu, Q.P., 2010. Protective effect of Xingnaojing and Xuesaitong injections on cerebral ischemic reperfusion injury in rats. Natl Med J China, (in Chinese),90(23):1645-1648. 

[8] Hou, Y.C., Tsai, S.Y., Lai, P.Y., 2008. Metabolism and pharmacokinetics of genipin and geniposide in rats. Food Chem Toxicol, 46(8):2764-2769. 

[9] Huang, P., Jiang, X.F., Zou, J.L., 2009. A novel GC-MS bioanalytical method for natural borneol and its application in investigating natural borneol distribution in mice. World Sci Technol, 11(6):821-827. 

[10] Huang, T.L., Ye, S.M., Ou, W.P., 2006. Comparative study of the pharmacokinetics of borneolum syntheticum and borneol in herbal preparations. Tradit Chin Drug Res Clin Pharmacol, (in Chinese),17(4):265-267. 

[11] Imanshahidi, M., Hosseinzadeh, H., 2006. The pharmacological effects of Salvia species on the central nervous system. Phytother Res, 20(6):427-437. 

[12] Kaste, M., Fogelholm, R., Rissanen, A., 1998. Economic burden of stroke and the evaluation of new therapies. Public Health, 112(2):103-112. 

[13] Koo, H.J., Lim, K.H., Jung, H.J., 2006. Anti-inflammatory evaluation of gardenia extract, geniposide and genipin. J Ethnopharm, 103(3):496-500. 

[14] Lee, J.H., Lee, D.U., Jeong, C.S., 2009.  Gardenia jasminoides Ellis ethanol extract and its constituents reduce the risks of gastritis and reverse gastric lesions in rats. Food Chem Toxicol, 47(6):1127-1131. 

[15] Li, C.Z., 1985. Anti-inflammatory effect of the volatile oil from Curcuma aromatica . China J Chin Mat Med, (in Chinese),10(3):38-40. 

[16] Li, F., Feng, J., Cheng, Q., 2007. Delivery of ¹²⁵I-cobrotoxin after intranasal administration to the brain: a microdialysis study in freely moving rats. Int J Pharm, 328(2):161-167. 

[17] Li, L., Yuan, Y., Jiang, X.H., 2006. Absorption mechanism of liposoluble components of Salvia miltiorrhiza with Caco-2 cell model. Chin Pharm J, (in Chinese),41(2):108-110. 

[18] Li, W.R., Liu, R., Huang, T.L., 2011. Chronotoxicology study of acute toxicity on natural borneol in mice. Lishizhen Med Mat Med Res, (in Chinese),22(8):1805-1806. 

[19] Li, Y.H., Sun, X.P., Zhang, Y.Q., 2008. The antithrombotic effect of borneol related to its anticoagulant property. Am J Chin Med, 36(4):719-727. 

[20] Liu, R., Zhang, L., Lan, X., 2011. Protection by borneol on cortical neurons against oxygen-glucose deprivation/reperfusion: involvement of anti-oxidation and anti-inflammation through nuclear transcription factor κB signaling pathway. Neuroscience, 176(10):408-419. 

[21] Liu, Y.H., Shao, F., Wang, Y., 2010. The damage of borneol and its preparation on gastric mucosa in rats. Qilu Pharm Affairs, (in Chinese),29(14):232-234. 

[22] Lon, H.K., Liu, D., Zhang, Q., 2011. Pharmacokinetic-pharmacodynamic disease progression model for effect of etanercept in Lewis rats with collagen-induced arthritis. Pharm Res, 28(7):1622-1630. 

[23] Longa, E.Z., Weinstein, P.R., Carlson, S., 1989. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 20(1):84-91. 

[24] Lu, Y., Du, S., Bai, J., 2011. Bioavailability and brain-targeting of geniposide in gardenia-borneol co-compound by different administration routes in mice. Int J Mol Sci, 13(11):14127-14135. 

[25] Lu, Y., Du, S.Y., Chen, X.L., 2011. Enhancing effect of natural borneol on the absorption of geniposide in rat via intranasal administration. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 12(2):143-148. 

[26] Meairs, S., Wahlgren, N., Dirnagl, U., 2006. Stroke research priorities for the next decade: a representative view of the European scientific community. Cerebrovasc Dis, 22(2-3):75-82. 

[27] Otegbayo, J.A., Talabi, O.A., Akere, A., 2006. Gastrointestinal complications in stroke survivors. Trop Gastroenterol, 27:127-130. 

[28] Pieniaszek, H.J., Davidson, A.F., Mcentegart, C.M., 1994. The effect of hepatic disease on the disposition of moricizine in humans. Biopharm Drug Dispos, 15(3):243-252. 

[29] Rodighiero, V., 1999. Effects of liver disease on pharmacokinetics. Clin Pharm, 37(5):399-431. 

[30] Rosenberg, G.A., Estrada, E.Y., Dencoff, J.E., 1998. Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke, 29(10):2189-2195. 

[31] State Science and Technology Commission, 1988. Regulation for the Administration of Affairs Concerning Experimental Animals. Order No. 2, (in Chinese),:

[32] Truong, D.T., Venna, V.R., McCullough, L.D., 2012. Deficits in auditory, cognitive, and motor processing following reversible middle cerebral artery occlusion in mice. Exp Neurol, 238(2):114-121. 

[33] Wang, W.J., Zhou, L.E., Bai, J.Y., 2000. Effects of musk glucoprotein on PAF production and cytosolic Ca²⁺ level in rat polymorphonuclear leukocytes in vitro . China J Chin Mat Med, (in Chinese),25(12):29-32. 

[34] Wu, S.D., Wan, Q., Xia, F., 2006. Dynamic changes of blood-brain barrier permeability and S100B protein level in serum after acute cerebral ischemia/reperfusion in rats. J Fourth Mil Med Univ, (in Chinese),27(10):902-904. 

[35] Xiao, Y.Y., Ping, Q.N., Chen, Z.P., 2007. The enhancing effect of synthetical borneol on the absorption of tetramethylpyrazine phosphate in mouse. Int J Pharm, 337(1-2):74-79. 

[36] Zeng, M., Pan, L., Qi, S., 2013. Systematic review of recent advances in pharmacokinetics of four classical Chinese medicines used for the treatment of cerebrovascular disease. Fitoterapia, 88:50-75. 

[37] Zhao, J.Y., Lu, Y., Du, S.Y., 2012. Comparative pharmacokinetic studies of borneol in mouse plasma and brain by different administrations. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 13(12):990-996.