Analysis of Brain Components and Mechanism of Danshen Ligustrazine Injection Based on UPLC-Q/TOF-MS and Network Pharmacology
DONG Qing-hai1, LIU Hui2, ZHOU Bai-song1, JIAO Yu-feng1, SI Yu1, LIU Jin-ping1, LI Ping-ya1, LIN Hong-qiang1*
1. Natural Products Research Center, College of Pharmacy, Jilin University, Changchun 130021, China; 2. Jilin Sichang Pharmaceutical Co., Ltd., Meihekou 135000, China
Abstract:OBJECTIVE To establish a method for determination of the components in Danshen Ligustrazine Injection which can penetrate into brain by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q/TOF-MS), and explore the mechanism of action by network pharmacology. METHODS UPLC-Q/TOF-MS technique was used to qualitatively analyze the prototype components penetrating into the brain of rats. TCMSP, DAVID and other databases were used to predict the targets and biological pathways of the components, and the brain component-target-biological pathway network was constructed by Cytoscape software. RESULTS Seven kinds of components were identified in the brain tissue of rats, involving 98 targets, which acted on 10 pathways including cGMP-PKG signaling pathway and calcium signaling pathway. CONCLUSION UPLC-Q/TOF-MS technique is a rapid and reliable method for analyzing the components penetrating into brain of Danshen Ligustrazine Injection. The mechanism of action and pharmacodynamic substances of the injection for the pharmacological effects in brain were preliminarily clarified by network pharmacology method.
董庆海, 刘慧, 周柏松, 焦玉凤, 司雨, 刘金平, 李平亚, 林红强. 基于UPLC-Q/TOF-MS和网络药理学分析丹参川芎嗪注射液入脑成分及作用机制[J]. 中国药学杂志, 2020, 55(21): 1795-1801.
DONG Qing-hai, LIU Hui, ZHOU Bai-song, JIAO Yu-feng, SI Yu, LIU Jin-ping, LI Ping-ya, LIN Hong-qiang. Analysis of Brain Components and Mechanism of Danshen Ligustrazine Injection Based on UPLC-Q/TOF-MS and Network Pharmacology. Chinese Pharmaceutical Journal, 2020, 55(21): 1795-1801.
ZAHNG X, CHEN M J. Analysis of Salvia Chuanxiong in the treatment of acute ischemic stroke effect[J]. Jilin Med J(吉林医学),2016,37(10):2417-2418.
[2]
WEI Y S, ZHU L X, HUANG X X, et al. Lipidomics study of protective effect of Salvia miltiorrhiza and Ligusticum chuanxiong on rats with focal cerebral ischemia injury based on UPLC-Q/TOF-MS[J]. Chin Tradit Herb Drugs(中草药),2019,50(2):408-417.
[3]
Ch.P(2015). VolⅠ(中国药典2015年版.一部)[S].2015:76-77.
[4]
LI H G, WANG H G, NIE X F, et al. Effecs of Danshen mixed extract from 3 genuine producing areas on nerve cells apoptosis in cerebral ischemia and reperfusion rats[J]. Hebei J Tradit Chin Med(河北中医),2016,38(10): 1515-1519.
[5]
PEI Y X. Pharmacological effects and clinical application of Chuanxiong[J]. Guide China Med(中国医药指南),2011,9(34):197-198.
[6]
LUO X, LUO Y. Progress in clinical application of salviae miltiorrhizae and ligustrazine hydrochloride injection[J]. Biped Health(双足与保健),2018,27(8):166-167.
[7]
WU F L, LI P Y, DONG Q H, et al. Absorbed components analysis of Zhitong Huazheng Capsules in rat serum by UPLC-Q-TOF/MS[J]. China J Chin Mater Med(中国中药杂志),2018,43(21):4339-4346.
[8]
HOPKINS A L. Network pharmacology[J]. Nat Biotechnol, 2007, 25(10):1110-1111.
[9]
HOPKINS, ANDREW L. Network pharmacology: the next paradigm in drug discovery[J]. Nat Chem Biol, 2008, 4(11):682-690.
[10]
TANG F, TANG Q, TIAN Y, et al. Network pharmacology-based prediction of the active ingredients and potential targets of Mahuang Fuzi Xixin decoction for application to allergic rhinitis[J]. J Ethnopharmacol, 2015, 176:402-412.
[11]
XIE J, GAO S, LI L, et al. Research progress and application strategy on network pharmacology in Chinese materia medica[J]. Chin Tradit Herb Drugs(中草药),2019,50(10):2257-2265.
[12]
LIANG X, LI H, LI S. A novel network pharmacology approach to analyse traditional herbal formulae: the Liu-Wei-Di-Huang pill as a case study[J]. Molecul Biosystems, 2014, 10(5):1014.
[13]
CHU Y B, SU X Q, LI D K, et al. Progress on quality control of traditional Chinese medicine injections[J]. Drug Eval Res(药物评价研究),2018, 41(3):345-353.
[14]
ZHANG T, WANG C Y, TIAN J W, et al. Protective effects of Danshensu on brain injury[J]. Chin Tradit Herb Drugs(中草药),2005,36(7):86-88.
[15]
XIAO J, WANG Z R, LUO H L. Effects of ligustrazine on cerebral circulation and cerebrovascular[J]. Pharmacol Clin Chin Mater Med(中药药理与临床),1994,(3):28-29.
[16]
ZHANG L J, LIU J Y, YAO C, et al. Research progress in pharmacological activities of senkyunolides[J]. Chin Pharm J(中国药学杂志),2015,50(13): 1081-1084.
[17]
DOCHERTY J R. Subtypes of functional α1-adrenoceptor[J]. Cell Molecul Life Sci, 2010, 67(3):405-417.
[18]
GERICKE A, MARTINKA P, NAZARENKO I, et al. Impact of 1-adrenoceptor expression on contractile properties of vascular smooth muscle cells[J]. AJP Regulat Integr Comp Physiol, 2007, 293(3):R1215-1221.
[19]
FAN L L, REN S, ZHOU H, et al. α1D-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes[J]. Acta Pharmacol Sin(中国药理学报), 2009, 30(12):1585-1593.
[20]
BARBANTI P, FOFI L, AURILIA C, et al. Dopaminergic symptoms in migraine[J]. Neurol Sci, 2013, 34(S1):67-70.
[21]
BENTON D, YOUNG H A. A Meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction?[J]. Int J Obe, 2016, 40(S1):12-21.
[22]
FENG W, CHEN X, GUAN S, et al. Relationship between MAPK1 gene polymorphism and gefitinib hepatotoxicity in NSCLC patients with activating EGFR mutations[J]. Acta Pharm Sin(药学学报),2018,53(5):760-764.
[23]
ZHOU R Y, WANG J J, HAN X M, et al. Effects of baicalin on the expression levels of synaptosomes′ dopamine releasing related factors in spontaneously hypertensive rats[J]. China J Tradit Chin Med Pharm(中华中医药杂志),2018,33(5):2007-2013.
[24]
WU L R. Vinpocetine reduces inflammatory response after cerebral ischemia-reperfusion by down-regulating TLR4 / MyD88 / NF-κB signaling pathway[D]. Chongqing: Third Military Medical University,2017.
[25]
SHENG Y M. Study on screening method of effective components for neuroprotection of traditional Chinese medicine based on "calcium signal pathway-blood-brain barrier" coupling[D]. Chengdu:Chengdu University of Traditional Chinese Medicine,2010.
[26]
XIAO H, MA X J, CHEN O M, et al. Gastrodin improves hippocampal neurogenesis by NO-cGMP-PKG signaling pathway in cerebral ischemic mice[J]. China J Chin Mater Med(中国中药杂志), 2019, 44(24):5451-5456.
[27]
YU W Y, YU J B, LUO G. Effect of Longhu Xingnao granule on intracerebral hemorrhage in rats and the regulation of cAMP/PKA/AQP4 signaling pathway[J]. Nanning: J Guangxi Med Univ(广西医科大学学报), 2018, 35(2):162-165.
[28]
CHEN W, WU Z Y. Role of vascular smooth muscle contraction signal pathway disorder in the formation of hyperdynamic circulation in portal hypertension[J]. J Surg Concepts Pract(外科理论与实践),2013,18(3):297-302.