Pharmacology progress on the main bioactive components of Ligusticum chuanxiong hort

doi:10.12092/j.issn.1009-2501.2018.11.018

Abstract

Abstract:

Ligusticum chuanxiong hort contains more than 100 kinds of pharmacological active ingredients. This study summarized its main bioactive components in pharmacology progress based on pharmacokinetics, and explained the pharmacokinetics and pharmacodynamics of ferulic acid, ligustilide, senkyunolide A, senkyunolide I and tetramethylpyrazine in detail. It will provide some new ideas and methods to the clinical application, deep development and utilization of Ligusticum chuanxiong hort.

Key words: chuanxiong, ferulic acid, ligustilide, senkyunolide, tetramethylpyrazine

CLC Number:

R282
R285

LI Haigang, HU Shaiping, ZHOU Yi, XU Dandan, MA Ning, TANG Jing, BAO Meihua, ZHENG Xiahui. Pharmacology progress on the main bioactive components of Ligusticum chuanxiong hort[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(11): 1302-1308.

References

［1］Hou YZ, Zhao GR, Yuan YJ, et al. Inhibition of rat vascular smooth muscle cell proliferation by extract of Ligusticum Chuanxiong and Angelica Sinensis［J］. J Ethnopharmacol,2005,100(1/2):140-144.
［2］Shan CS, Xu QQ, Shi YH, et al. Chuanxiong formulae for migraine: A systematic review and meta-analysis of high-quality randomized controlled trials［J］. Front Pharmacol,2018,9:589.
［3］Li Y, Xu C, Zhang Q, et al. In vitro anti-Helicobacter pylori action of 30 Chinese herbal medicines used to treat ulcer diseases［J］. J Ethnopharmacol,2005,98(3):329-333.
［4］Li W, Tang Y, Chen Y, et al. Advances in the chemical analysis and biological activities of Chuanxiong［J］. Molecules,2012,17(9):10614-10651.
［5］唐于平，段金廒，范欣生，等. 芳香酸类成分在活血化瘀方中的作用分析［J］. 世界科学技术-中医药现代化,2008, 10(4):38-42.
［6］Prime-Chapman HM, Fearn RA, Cooper AE, et al. Differential multidrug resistance-associated protein 1 through 6 isoform expression and function in human intestinal epithelial Caco-2 cells［J］. J Pharmacol Exp Ther, 2004, 311(2):476-484.
［7］Wang L, Sweet DH. Potential for food-drug interactions by dietary phenolic acids on human organic anion transporters 1 (SLC22A6), 3 (SLC22A8), and 4 (SLC22A11)［J］. Biochem Pharmacol, 2012,84(8):1088-1095.
［8］Li Y, Liu C, Zhang Y, et al. Pharmacokinetics of ferulic acid and potential interactions with Honghua and clopidogrel in rats［J］. J Ethnopharmacol, 2011,137(1):562-567.
［9］Kawabata K, Yamamoto T, Hara A, et al. Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats［J］. Cancer Lett, 2000,157(1):15-21.
［10］ Li JM, Zhao YH, Zhong GC, et al. Synthesis of ferulic acid derivatives and their inhibitory effect on platelet aggregation［J］. Yao Xue Xue Bao,2011,46(3):305-310.
［11］Yang GW, Jiang JS, Lu WQ. Ferulic acid exerts anti-angiogenic and anti-tumor activity by targeting fibroblast growth factor receptor 1-mediated angiogenesis［J］. Int J Mol Sci,2015,16(10):24011-24031.
［12］Tomas-Barberan F, Garcia-Villalba R, Quartieri A, et al. In vitro transformation of chlorogenic acid by human gut microbiota［J］. Mol Nutr Food Res,2014,58(5):1122-1131.
［13］Del RD, Stalmach A, Calani L, et al. Bioavailability of coffee chlorogenic acids and green tea flavan-3-ols［J］. Nutrients,2010,2(8):820-833.
［14］张星海，王岳飞. 茶多酚与绿原酸生物活性的比较研究［J］. 茶叶科学,2007，27(1):39-44.
［15］Wang LH, Hsu KY, Uang YS, et al. Caffeic acid improves the bioavailability of L-dopa in rabbit plasma［J］. Phytother Res, 2010,24(6):852-858.
［16］孙皓熠，郝宝燕，张浩超，等. 咖啡酸研究概况［J］. 食品与药品,2017,19(2):151-154.
［17］张晓琳，徐金娣，朱玲英，等. 中药川芎研究新进展［J］. 中药材,2012,35(10):1706-1711.
［18］Zheng Q, Tang Y, Hu PY, et al. The influence and mechanism of ligustilide, senkyunolide I, and senkyunolide A on echinacoside transport through MDCK-MDR1 cells as blood-brain barrier in vitro model［J］. Phytother Res,2018,32(3):426-435.
［19］Hu PY, Liu D, Zheng Q, et al. Elucidation of transport mechanism of paeoniflorin and the influence of ligustilide, senkyunolide I and senkyunolide A on paeoniflorin transport through Mdck-Mdr1 cells as blood-brain barrier in vitro model［J］. Molecules,2016,21(3):300.
［20］Li SL, Yan R, Tam YK, et al. Post-harvest alteration of the main chemical ingredients in Ligusticum Chuanxiong Hort. (Rhizoma Chuanxiong)［J］. Chem Pharm Bull (Tokyo),2007,55(1):140-144.
［21］房鑫，熊智，林晓，等. 藁本内酯的稳定性及其主要转化产物研究(英文)［J］. 天然产物研究与开发,2014,26(9):1339-1344.
［22］Yan R, Ko NL, Li SL, et al. Pharmacokinetics and metabolism of ligustilide, a major bioactive component in Rhizoma Chuanxiong, in the rat［J］. Drug Metab Dispos,2008,36(2):400-408.
［23］Shi Y, He L, Wang S. Determination of ligustilide in rat blood and tissues by capillary gas chromatography/mass spectrometry［J］. Biomed Chromatogr,2006,20(10):993-998.
［24］Ding C, Sheng Y, Zhang Y, et al. Identification and comparison of metabolites after oral administration of essential oil of Ligusticum Chuanxiong or its major constituent ligustilide in rats［J］. Planta Med,2008,74(14):1684-1692.
［25］Zhang L, Du JR, Wang J, et al. Z-ligustilide extracted from Radix Angelica Sinensis decreased platelet aggregation induced by ADP ex vivo and arterio-venous shunt thrombosis in vivo in rats［J］. Yakugaku Zasshi,2009,129(7):855-859.
［26］Lu Q, Qiu TQ, Yang H. Ligustilide inhibits vascular smooth muscle cells proliferation［J］. Eur J Pharmacol,2006,542(1/2/3):136-140.
［27］Liang MJ, He LC, Yang GD. Screening, analysis and in vitro vasodilatation of effective components from Ligusticum Chuanxiong［J］. Life Sci,2005,78(2):128-133.
［28］Shi Y, Xiao L, Yin Y, et al. Ligustilide inhibits tumour necrosis factor-alpha-induced autophagy during C2C12 cells differentiation［J］. Biomed Pharmacother,2015,69:42-46.
［29］Peng HY, Du JR, Zhang GY, et al. Neuroprotective effect of Z-ligustilide against permanent focal ischemic damage in rats［J］. Biol Pharm Bull,2007,30(2):309-312.
［30］Li J, Yu J, Ma H, et al. Intranasal pretreatment with Z-ligustilide, the main volatile component of Rhizoma Chuanxiong, confers prophylaxis against cerebral ischemia via Nrf2 and HSP70 signaling pathways［J］. J Agric Food Chem,2017,65(8):1533-1542.
［31］Yan R, Lin G, Ko NL, et al. Low oral bioavailability and pharmacokinetics of senkyunolide a, a major bioactive component in Rhizoma Chuanxiong, in the rat［J］. Ther Drug Monit,2007,29(1):49-56.
［32］Zhao X, Ma T, Zhang C, et al. Simultaneous determination of senkyunolide I and senkyunolide H in rat plasma by LC-MS: application to a comparative pharmacokinetic study in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract［J］. Biomed Chromatogr,2015,29(9):1297-1303.
［33］Chan SS, Cheng TY, Lin G. Relaxation effects of ligustilide and senkyunolide A, two main constituents of Ligusticum Chuanxiong, in rat isolated aorta［J］. J Ethnopharmacol,2007,111(3):677-680.
［34］Gong S, Zhang J, Guo Z, et al. Senkyunolide A protects neural cells against corticosterone-induced apoptosis by modulating protein phosphatase 2A and alpha-synuclein signaling［J］. Drug Des Devel Ther,2018,12:1865-1879.
［35］杨学东，伍勋，胡立翠，等. 不同溶剂对川芎药材中有效成分提取效果的影响［J］. 中国中药杂志,2012,37(13):1942-1945.
［36］He C Y, Wang S, Feng Y, et al. Pharmacokinetics, tissue distribution and metabolism of senkyunolide I, a major bioactive component in Ligusticum Chuanxiong Hort. (Umbelliferae)［J］. J Ethnopharmacol,2012,142(3):706-713.
［37］Xiong YK, Lin X, Liang S, et al. Identification of senkyunolide I metabolites in rats using ultra performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry［J］. J Pharm Biomed Anal,2013,81-82:178-186.
［38］马聪，熊耀坤，马诗瑜，等. 洋川芎内酯I在大鼠尿液和胆汁中的排泄［J］. 中国实验方剂学杂志,2015,21(19):75-79.
［39］Hu YY, Wang Y, Liang S, et al. Senkyunolide I attenuates oxygen-glucose deprivation/reoxygenation-induced inflammation in microglial cells［J］. Brain Res,2016,1649(Pt A):123-131.
［40］Hu Y, Duan M, Liang S, et al. Senkyunolide I protects rat brain against focal cerebral ischemia-reperfusion injury by up-regulating p-Erk1/2, Nrf2/HO-1 and inhibiting caspase 3［J］. Brain Res,2015,1605:39-48.
［41］Wang YH, Liang S, Xu DS, et al. Effect and mechanism of senkyunolide I as an anti-migraine compound from Ligusticum chuanxiong［J］. J Pharm Pharmacol,2011,63(2):261-266.
［42］Zhu M, Tang Y, Duan JA, et al. Roles of paeoniflorin and senkyunolide I in SiWu decoction on antiplatelet and anticoagulation activities［J］. J Sep Sci,2010,33(21):3335-3340.
［43］Chen F, Wang T, Wang J, et al. Levistolide A overcomes P-glycoprotein-mediated drug resistance in human breast carcinoma cells［J］. Acta Pharmacol Sin,2008,29(4):458-464.
［44］Yang Y, Zhang Y, Wang L, et al. Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells［J］. Cell Physiol Biochem,2017,42(3):929-938.
［45］Li H, Zhang C, Fan R, et al. The effects of Chuanxiong on the pharmacokinetics of warfarin in rats after biliary drainage［J］. J Ethnopharmacol,2016,193:117-124.
［46］ Erlinger S. Review article: new insights into the mechanisms of hepatic transport and bile secretion［J］. J Gastroenterol Hepatol,1996,11(6):575-579.
［47］Guo M, Liu Y, Shi D. Cardiovascular actions and therapeutic potential of tetramethylpyrazine (active component isolated from Rhizoma Chuanxiong): roles and mechanisms［J］. Biomed Res Int,2016,2016:2430329.
［48］蔡伟，董善年，楼雅卿. 正常人口服磷酸川芎嗪的药代动力学研究［J］. 药学学报,1989,24(12):881-886.
［49］江骥，姜国辉，叶云鹏，等. 川芎嗪的体内代谢［J］. 中国医学科学院学报,1993,15(2):79-82.
［50］谭妍，庄笑梅，沈国林，等. 川芎嗪的肝微粒体代谢动力学及代谢表型研究［J］. 药学学报,2014,49(3):374-379.
［51］Meng D, Lu H, Huang S, et al. Comparative pharmacokinetics of tetramethylpyrazine phosphate in rat plasma and extracellular fluid of brain after intranasal, intragastric and intravenous administration［J］. Acta Pharm Sin B,2014,4(1):74-78.
［52］Lu D, Shao HT, Ge WP, et al. Ginsenoside-Rb1 and tetramethylpyrazine phosphate act synergistically to prevent dilated cardiomyopathy in cTnTR141W transgenic mice［J］. J Cardiovasc Pharmacol,2012,59(5):426-433.
［53］Lv L, Jiang SS, Xu J, et al. Protective effect of ligustrazine against myocardial ischaemia reperfusion in rats: the role of endothelial nitric oxide synthase［J］. Clin Exp Pharmacol Physiol,2012,39(1):20-27.
［54］孙明月，郭春雨，王景尚，等. 铁调素高表达与内皮损伤的相关性及川芎嗪的干预作用［J］. 中草药,2015,46(15):2265-2269.
［55］陈章强，洪浪，王洪，等. 川芎嗪对急性冠脉综合征患者介入术后血小板活化及血管内皮功能的影响［J］. 中国中西医结合杂志,2007,27(12):1078-1081.
［56］Zhang L, Deng M, Zhou S. Tetramethylpyrazine inhibits hypoxia-induced pulmonary vascular leakage in rats via the ROS-HIF-VEGF pathway［J］. Pharmacology,2011,87(5/6):265-273.
［57］Li WM, Liu HT, Li XY, et al. The effect of tetramethylpyrazine on hydrogen peroxide-induced oxidative damage in human umbilical vein endothelial cells［J］. Basic Clin Pharmacol Toxicol,2010,106(1):45-52.
［58］Gao X, Zhao XL, Zhu YH, et al. Tetramethylpyrazine protects palmitate-induced oxidative damage and mitochondrial dysfunction in C2C12 myotubes［J］. Life Sci,2011,88(17/18):803-809.
［59］高美华，张丽，李冰，等. 川穹嗪对AngⅡ诱导的大鼠心肌肥大细胞JAK-STAT通路作用［J］. 细胞与分子免疫学杂志,2011,27(5):519-521.
［60］Yang Y, Li Z H, Liu H, et al. Inhibitory effect of tetramethylpyrazine preconditioning on overload training-induced myocardial apoptosis in rats［J］. Chin J Integr Med,2015,21(6):423-430.
［61］Wang JQ, Zhang L, Tao XG, et al. Tetramethylpyrazine upregulates the aquaporin 8 expression of hepatocellular mitochondria in septic rats［J］. J Surg Res,2013,185(1):286-293.
［62］Li M, Zhang X, Cui L, et al. The neuroprotection of oxymatrine in cerebral ischemia/reperfusion is related to nuclear factor erythroid 2-related factor 2 (nrf2)-mediated antioxidant response: role of nrf2 and hemeoxygenase-1 expression［J］. Biol Pharm Bull,2011,34(5):595-601.
［63］Lin JB, Zheng CJ, Zhang X, et al. Effects of tetramethylpyrazine on functional recovery and neuronal dendritic plasticity after experimental stroke［J］. Evid Based Complement Alternat Med,2015,2015:394926.
［64］Michel HE, Tadros MG, Esmat A, et al. Tetramethylpyrazine ameliorates rotenone-induced Parkinson's Disease in rats: involvement of its anti-inflammatory and anti-apoptotic actions［J］. Mol Neurobiol,2017,54(7):4866-4878.
［65］Lee LM, Liu CF, Yang PP. Effect of tetramethylpyrazine on lipid peroxidation in streptozotocin-induced diabetic mice［J］. Am J Chin Med,2002,30(4):601-608.
［66］Gong X, Wang Q, Tang X, et al. Tetramethylpyrazine prevents contrast-induced nephropathy by inhibiting p38 MAPK and FoxO1 signaling pathways［J］. Am J Nephrol,2013,37(3):199-207.
［67］Lan L,Guo M,Ai Y,et al.Tetramethylpyrazine blocks TFAM degradation and up-regulates mitochondrial DNA copy number by interacting with TFAM［J］.Biosci Rep,2017,37(3):DOI 10.1042/BSR20170319.
［68］Zhao Y, Liu Y, Chen K. Mechanisms and clinical application of tetramethylpyrazine (an interesting natural compound isolated from Ligusticum Wallichii): current status and perspective［J］. Oxid Med Cell Longev,2016,2016:2124638.
［69］张伟杰，王鹏，杨明俊，等. 川芎、赤芍多糖活性分析及其比较［J］. 中药材,2011,34(10):1569-1574.
［70］Helander IM, Nurmiaho-Lassila EL, Ahvenainen R, et al. Chitosan disrupts the barrier properties of the outer membrane of gram-negative bacteria［J］. Int J Food Microbiol,2001,71(2/3):235-244.
［71］Zou YF, Fu YP, Chen XF, et al. Purification and partial structural characterization of a complement fixating polysaccharide from Rhizomes of Ligusticum Chuanxiong［J］. Molecules,2017,22(2):287.
［72］李川. 中药多成分药代动力学研究:思路与方法［J］. 中国中药杂志,2017,42(4):607-617.

[1]	CAO Xuefen, LENG Yufang, HAN Xiaoxia, HOU Xiaoyu, LYU Xingjiao, Janvier NIBARUTA. Tetramethylpyrazine protected against intestinal ischemia-reperfusion injury induced pyroptosis by inhibiting NLRP3 inflammasome activation [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(11): 1201-1208.
[2]	LIU Yizhen, REN Lingxuan, YANG Jianjun, HE Jianyu, LIU Xiaojun, WANG Long, LIN Rong. Study on the screening of active constituents of Taohong Siwu Decoction and the protective effect of ferulic acid on myocardial injury [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(5): 505-515.
[3]	DING Xueming, CHEN Tianpeng, XU Qiang, HE Huan, HE Ming. Tetramethylpyrazine attenuates doxorubicin induced cardiotoxicity through 14-3-3γ/Bcl-2 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(4): 361-367.
[4]	FU Ai, XU Tiantian, YANG Zhen, HAN Qiang, DOU Xiaobing, LI Songtao. Ferulic acid protects palmitic acid-induced lipotoxicity in hepatocytes via inhibiting p38 MAPK [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(2): 137-143.
[5]	ZHONG Zhengling，ZHANG Fei，JIANG Yuhua，ZHANG Weiting，TONG Jiucui，LI Juan，CHU Jiru，XIE Haitang. Protective effects of Ferulic acid on acute liver injury induced by D-GalN/LPS in mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(12): 1335-1339.
[6]	FU Yongjin, XIA Xueyi, ZHANG Xiaomu, LIU Yanbo, PAN Jingqiang, LV Junhua. Effects of tetramethylpyrazine on the down-regulation of HMGB1 expression and reducing contents of RAGEs in diabetic nephropathy rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(8): 846-851.
[7]	ZHANG Ze-yu, LIU Dan, WANG Qing, LUO Yong, LIAO Zhang-ping, TANG Lei, HE Ming. Protective effect of tetramethylpyrazine preconditioning on rat myocardium with non-invasive limb ischemia preconditioning [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(12): 1353-1358.
[8]	YANG Wen-hui, GONG Guo-qing, ZHOU Yi, ZHANG Zhi-xian, LI Jie. Effect and mechanism of tetramethylpyrazine on antithrombotic [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(3): 241-244.
[9]	HUANG Mei-yan, LI Wei-xia, TANG Yu-ping, GUO Jian-ming, SHANG Er-xin, LIU Xin, LIU Li, DUAN Jin-ao. Comparative study on enriching blood effect of Fo-shou-san with different ethanol extraction [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(8): 841-846.
[10]	SUN Yu-ming, LOU Jian-Tao, HUANG Guang-xiang, SUN Jun. Study on the therapeutic effects of ferulic acid sodium in cerebral hemorrhage model rats induced by collagenase and its mechanism [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(12): 1377-1382.
[11]	WANG Wen-ping, CAO Qi-chen, WANG Hua-wei, LV Yu-ping. Pharmacokinetic study on different compatibilities of Dangguibuxue Tang [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(6): 659-663.
[12]	CHEN Wen-qian, HU Yu-hui, ZHANG Yan-qing, ZHANG Guan-min, LI Liang, ANG Wei-ning, LU Wei. Population pharmacokinetics of Guanxin Ⅱ prescription [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(10): 1138-1143.
[13]	WANG Su-jun, ZHANG Zhi-wei, ZHAO Yan-hong, ZHANG Zhen-qing, XIE Hai-tang, RUAN Jin-xiu. Establishment of in situ perfused rat intestine-liver model for evaluation on chlorogenic acid metabolism [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(12): 1340-1344.
[14]	WANG Wen-wu, DAI Xi-hu, OUYANG Xue-nong. Experimental study of effects of tetramethylpyrazine on Lewis lung carci-noma in mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(4): 421-423.
[15]	WANG Xia, LI Qi-Xiong. Effects of tetramethylpyrazine on proliferation of rat glomerular mesangial cells induced by lipopolysaccharide and levels of intercellular adhesion molecule-1 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(4): 420-422.