As one of the most frequently used medicinal herbs in China, Chuanxiong Rhizoma (Chuanxiong) is notable for its beneficial effects in alleviation of cardio- and cerebro- vascular disorders. Results from previous phytochemical, phar macological and pharmacokinetic studies supported the contributions of 10 main components, namely ferulic acid ( 3 ), senkyunolide I ( 4 ), senkyunolide H ( 5 ), senkyunolide A ( 6 ), coniferylferulate ( 7 ), Z-ligustilide ( 8 ), sedanolide ( 9 ), 3-butylidenephthalide ( 10 ), riligustilide ( 11 ) and levistolide A ( 12 ), for therapeutic outcomes of the herb. To prepare a Chuanxiong extract, which is selectively enriched with these main components, the supercritical fluid extraction (SCFE) technique using CO 2 was chosen in the present study due to its superiority in extraction of lipophilic components, especially thermo-labile components from natural products. Eight Chuanxiong samples were extracted under different SCFE conditions. Contents of 3 - 12 in SCFE extracts and remained in herbal residues were determined using HPLC-UV and compared with those in 95% ethanol extracts of the respective herbal samples. The results showed that contents of 3 - 12 were generally enriched by SCFE with higher recoveries achieved for lipophilic constituents, including the three most abundant constituents 6 , 7 and 8 . Moreover, extraction yield of the less lipophilic 3 , 4 and 5 was improved by adding ethanol as entrainer. Higher flow rate of CO 2 (10 - 13 L /h vs 9 - 12 L /h) enhanced the overall extraction, while lower temperature (32℃ vs 40 ℃ ) reduced degradation of thermo-labile compounds, in particular 7 , 8 and 10 . Our es tablished SCFE condition yielded high extraction recoveries for both total (75.6%) and three major chemical ingredients ( 6 : 83.5%, 7 : 77%, 8 : 78.3%) from Chuanxiong with an adequate overall reproducibility, demonstrating a successful application of SCFE in selective enrichment of certain ingredients and efficient extraction of thermo-labile components from medicinal herbs using specifically designed SCFE conditions.
Keywordslinge@cuhk.edu.hk
S. L. Li, S. S.-K. Chan, G. Lin, L. Ling, R. Yan, H. S. Chung and Y. K. Tam, “Simultaneous Analysis of the Main Chemical Ingredients of Ligusticum Chuanxiong by On-Line High Performance Liquid Chromatography-Diode Array Detector-Mass Spectrometry,” Planta Medica, Vol. 69, No. 5, 2003, pp. 445-451. doi:10.1016/j.jpba.2004.09.054
R. Yan, S. L. Li, H. S. Chung, Y. K. Tam and G. Lin, “Simultaneous Quantification of Twelve Bioactive Components of Ligusticum Chuanxiong Hort. by High-Performance Liquid Chromatography,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 37, No. 1, 2005, pp. 87-95. doi:10.1016/j.jpba.2004.09.054
W. C. Ko, J. R. Sheu, S. H. Tzeng and C. M. Chen, “The Selective Antianginal Effect without Changing Blood Pressure of Butylidenephthalide in Conscious Rats,” Planta Medica, Vol. 64, No. 3, 1998, pp. 229-232. doi:10.1055/s-2006-957415
W. C. Ko, C. C. Liao, C. H. Shih, C. B. Lei and C. M. Chen, “Relaxant Effects of Butylidenephthalide in Isolated Dog Blood Vessels,” Planta Medica, Vol. 68, No. 11, 2002, pp. 1004-1009. doi:10.1055/s-2002-35671
T. Naito, K. Kubota, Y. Shimoda, T. Sato, Y. Ikeya, M. Okada and M. Maruno, “Effects of Constituents in a Chinese Crude Drug, Ligustici Chuanxiong Rhizoma on Vasoconstriction and Blood Viscosity,” Natural Medicine, Vol. 49, 1995, pp. 288-292.
C. M. Teng, W. Y. Chen, W. C. Ko and C. Ouyang, “Antiplatelet Effect of Butylidenephthalide,” Biochimica et Biophysica Acta, Vol. 924, No. 3, 1987, pp. 375-382. doi:10.1016/0304-4165(87)90151-6
S. S.-K. Chan, A. O.-K. Choi, R. L. Jones and G. Lin, “Mechanisms Underlying the Vasorelaxing Effects of Butylidenephthalide, an Active Constituent of Ligusticum Chuanxiong, in Rat Isolated Aorta,” European Journal of Pharmacology, Vol. 537, No. 1-3, 2006, pp. 111-117. doi:10.1016/j.ejphar.2006.03.015
S. S.-K. Chan, T. Y. Cheng and G. Lin, “Relaxation Effects of Ligustilide and Senkyunolide A, Two Main Constituents of Ligusticum Chuanxiong, in Rat Isolated Aorta,” Journal of Ethnopharmacology, Vol. 111, No. 3, 2007, pp. 677-680. doi:10.1016/j.jep.2006.12.018
S. S.-K. Chan, R. L. Jones and G. Lin, “Synergistic Interaction between the Ligusticum Chuanxiong Constituent Butylidenephthalide and the Nitric Oxide Donor Sodium Nitroprusside in Rat Isolated Aorta,” Journal of Ethnopharmacology, Vol. 122, No. 2, 2008, pp. 308-312. doi:10.1016/j.jep.2009.01.002
W. L.-T. Kan, C. H. Cho, J. A. Rudd and G. Lin, “Study of the anti-Proliferative Effects of Phthalides from Angelica Sinensis on Colon Cancer Cells,” Journal of Ethnopharmacology, Vol. 120, No. 1, 2008, pp. 36-43. doi:10.1016/j.jep.2008.07.027
L. Liu , Z. Q. Ning, S. Shan, K. Zhang, T. Deng, X. P. Lu and Y. Y. Cheng, “Phthalide Lactones from Ligusticum Chuanxiong Inhibit Lipopolysaccharide-Induced TNF-Alpha Production and TNF-Alpha-Mediated NF-KappaB Activation,” Planta Medica, Vol. 71, No. 9, 2005, pp. 808-813. doi:10.1055/s-2005-871231
J. W. Chung, R. J. Choi, E. K. Seo, J. W. Nam, M. S. Dong, E. M. Shin, L. Y. Guo and Y. S. Kim, “Anti-Inflammatory Effects of (Z)-Ligustilide through Suppression of Mitogen-Activated Protein Kinases and Nuclear Factor-κB Activation Pathways,” Archives of Pharmacal Research, Vol. 35, No. 4, 2012, pp. 723-732. doi:10.1007/s12272-012-0417-z
Z. Feng, Y. Lu, X. Wu, P. Zhao, J. Li, B. Peng, Z. Qian and L. Zhu, “Ligustilide Alleviates Brain Damage and Improves Cognitive Function in Rats of Chronic Cerebral Hypoperfusion,” Journal of Ethnopharmacology, Vol. 144, No. 2, 2012, pp. 313-321. doi:10.1016/j.jep.2012.09.014
T. F. Lee, Y. L. Lin and Y. T. Huang, “Studies on antiProliferative Effects of Phthalides from Ligusticum Chuanxiong in Hepatic Stellate Cells,” Planta Medica, Vol. 73, No. 6, 2007, pp. 527-534. doi:10.1097/FTD.0b013e31802c5862
R. Yan, G. Lin, N. L. Ko and Y. K. Tam, “Low Oral Bioavailability and Pharmacokinetics of Senkyunolide A, a Major Bioactive Component in Rhizoma Chuanxiong, in the Rat,” Therapeutic Drug Monitoring, Vol. 29, No. 1, 2007, pp. 49-56. doi:10.1097/FTD.0b013e31802c5862
R. Yan, N. L. Ko, S. L. Li, Y. K. Tam and G. Lin, “Pharmacokinetics and Metabolism of Ligustilide, a Major Bioactive Component in Rhizoma Chuanxiong, in the Rat,” Drug Metabolism and Disposition, Vol. 36, No. 2, 2008, pp. 400-408. doi:10.1124/dmd.107.017707
R. Yan, N. L. Ko, B. Ma, Y. K. Tam and G. Lin, “Pharmacokinetic Interaction among co-Existing Ingredient Leading to Significant Systemic Exposure of Z-Butylidenephthalide, a Minor Ingredient in Chuanxiong Rhizoma, in Rat,” Current Drug Metabolism, Vol. 13, No. 5, 2012, pp. 524-534. doi:10.2174/1389200211209050524
S. L. Li, R. Yan, Y. K. Tam and G. Lin, “Post-Harvest Alteration of the Main Chemical Ingredients in Ligusticum Chuanxiong Hort. (Rhizoma Chuanxiong),” Chemical and Pharmaceutical Bulletin, Vol. 55, No. 1, 2007, pp. 140-144. doi:10.1248/cpb.55.140
S. Lee, M. K. Park, K. H. Kim and Y.-S. Kim, “Effect of Supercritical Carbon Dioxide Decaffeination on Volatile Components of Green Teas,” Journal of Food Science, Vol. 72, No. 7, 2007, pp. S497-S502. doi:10.1111/j.1750-3841.2007.00446.x
J. P. Coelho, A. F. Cristino, P. G. Matos, A. P. Rauter, B. P. Nobre, R. L. Mendes, J. G. Barroso, A. Mainar, J. S. Urieta, J. M. Fareleira, H. Sovová and A. F. Palavra, “Extraction of Volatile Oil from Aromatic Plants with Supercritical Carbon Dioxide: Experiments and Modeling,” Molecules, Vol. 17, No. 9, 2012, pp. 10550-10573. doi:10.3390/molecules170910550
S. M. Pourmortazavi and S. S. Hajimirsadeghi, “Super-critical Fluid Extraction in Plant Essential and Volatile Oil Analysis,” Journal of Chromatography A, Vol. 1163, No. 1-2, 2007, pp. 2-24. doi:10.1016/j.chroma.2007.06.021
M. A. McHugh and V. J. Krukonis, “Supercritical Fluid Extraction: Principles and Practice (Butterworth-Heinemann Series in Chemical Engineering),” Butterworth-Heinemann, Oxford, 1994.
Q. Lang and C. M. Wai, “Supercritical Fluid Extraction in Herbal and Natural Product Studies—A Practical Review,” Talanta, Vol. 53, No. 4, 2001, pp. 771-782. doi:10.1016/S0039-9140(00)00557-9
M. Mukhopadhyay, “Natural Extracts Using Supercritical Carbon Dioxide,” CRC Press, Boca Raton, 2000. doi:10.1248/cpb.35.1427
Z. Y. Hong, X. Z. Wang, J. Le, D. C. Zhang, Y. F. Chai and Z. L. Liu, “Supercritical Fluid Extraction of Essential Oil from Dry Rhizome of Ligusticum Chuanxiong Hort and Their Characterization by GC/MS,” Journal of Chinese Pharmaceutical Sciences, Vol. 11, No. 2, 2002, pp. 31-34. doi:10.1016/j.juro.2006.06.135
Q. Ruan, Y. Zhang, Y. Y. Hu and X. X. He, “Influences of Different Extraction Mathods on the Chemical Contents of Chuanxiong Essential Oils,” China Journal of Chinese Materia Medica, Vol. 28, No. 6, 2003, pp. 572-574.
G. T. Wu, L. F. Shi, J. H. Hu and L. Li, “The Determination of Ligustilide in Ligusticum Chuanxiong Hort. by Supercritical Fluid Extraction,” Acta Pharmaceutica Sinica, Vol. 33, No. 6, 1998, 457-460.
Y. F. Yuan, J. Zhou, X. M. Zheng and L. Li, “Studies on Volatile Oil in Ligusticum Chuanxiong by Supercritical Fluid Extraction,” Chinese Pharmaceutical Journal, Vol. 35, No. 2, 2000, pp. 84-87.
X. L. Guo, Y. F. Feng, H. M. Liang, G. F. Chen and Y. Gao, “Analysis of Chemical Constituents in Supercritical CO2 Extract of Ligusticum Chuanxiong Hort. By GC-MS,” Chinese Journal of Pharmaceuticals, Vol. 36, No. 8, 2005, pp. 472-474.
Y. Lan, L. Zheng, Y. Huang, A. Wang, Y. Li, X. He and Y. Wang, “Studies on Extraction of Ligusticum Chuanxiong in Hongye Xintong Soft Capsule by Super Critical Fluid Extraction,” Zhongguo ZhongYao ZaZhi, Vol. 34, No. 2, 2009, pp. 161-164.
The State Pharmacopoeia Commission of China, “Rhizoma Chuanxiong,” Pharmacopoeia of the People’s Republic of China, Chemical Industry Press, Beijing, 2010, p. 38.
M. Kobayashi, M. Fujita and H. Mitsuhashi, “Components of Cnidium Officinale Makino: Occurrence of Pregnenolone, Coniferyl Ferulate and Hydroxyphthalide,” Chemical & Pharmaceutical Bulletin, Vol. 32, No. 9, 1984, pp. 3770-3773. doi:10.1248/cpb.32.3770
M. Kobayashi, M. Fujita and H. Mitsuhashi, “Studies on the Constituents of Umbelliferae Plants. XV. Constituents of Cnidium Officinale: Occurrence of Pregnenolone, Coniferyl Ferulate and Hydroxyphthalide,” Chemical & Pharmaceutical Bulletin, Vol. 35, No. 4, 1987, pp. 1427-1433. doi:10.1248/cpb.35.1427