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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

General Research Article

Exploration of the Two-Way Adjustment Mechanism of Rhei Radix et Rhizoma for Cardiovascular Diseases

Author(s): Lishan Pei, Xia Shen, Kai Qu*, Conge Tan*, Junbo Zou, Yanxia Wang and Fan Ping

Volume 23, Issue 10, 2020

Page: [1100 - 1112] Pages: 13

DOI: 10.2174/1386207323666200521120308

Price: $65

Abstract

Aim and Objective: Myocardial infarction, cerebral infarction, and other diseases caused by vascular obstruction have always jeopardized human life and health. Several reports indicate that Rhei Radix et Rhizoma has a good clinical effect in the prevention and treatment of cardiovascular diseases. Owing to the complexity of herbal medicine, the pharmacodynamic mechanism of Rhei Radix et Rhizoma is still unclear. The objectives of this study were to explore the two-way adjustment mechanism of Rhei Radix et Rhizoma and provide a new solution for the prevention and treatment of cardiovascular disease.

Materials and Methods: This study used data mining, reverse pharmacophore matching, network construction, GO and KEGG Analysis, and molecular docking to investigate the two-way adjustment mechanism of Rhei Radix et Rhizoma. The methods used were based on systems pharmacology and big data analysis technology.

Results: The results suggest that Rhei Radix et Rhizoma uses a two-way adjustment of activating blood circulation, as well as blood coagulation in the prevention and treatment of cardiovascular diseases. The components involved in activating blood circulation are mainly anthraquinone components. The corresponding targets are NOS2, NOS3, CALM1, and the corresponding pathways are calcium signaling pathway, VEGF signaling pathway, platelet activation, and the PI3K-Akt signaling pathway. For blood coagulation, the components are mainly tannin components; the corresponding targets are F2, F10, ELANE, and the corresponding pathways are the neuroactive ligand-receptor interaction, complement and coagulation cascades.

Conclusion: This study indicated that Rhei Radix et Rhizoma exerts the two-way adjustment of activating blood circulation and blood coagulation in the prevention and treatment of cardiovascular diseases. It can make up for the side effects of the existing blood circulation drugs for cardiovascular disease, only activating blood circulation, and the uncontrollable large-area bleeding due to the long-term use of the drugs. This study provides a material basis for the development of new blood-activating drugs based on natural medicine.

Keywords: Two-way adjustment mechanism, Rhei Radix et Rhizoma, activating blood circulation and blood coagulation, Molecular docking, cardiovascular disease, systems pharmacology.

[1]
Schuett, K.A.; Lehrke, M.; Marx, N.; Burgmaier, M. High-risk cardiovascular patients: clinical features, comorbidities, and interconnecting mechanisms. Front. Immunol., 2015, 6, 591.
[http://dx.doi.org/10.3389/fimmu.2015.00591] [PMID: 26635805]
[2]
Guo, L.J.; Bao, Y. Analysis on the research status of system dynamics model in the cardiovascular diseases at home and abroad. Chin. Gen. Pract., 2017, 20, 2925-2929.
[3]
Lillo, N.; Palomo-Vélez, G.; Fuentes, E.; Palomo, I. Role of physical activity in cardiovascular disease prevention in older adults. Sport Sci. Health, 2015, 11(3), 227-233.
[http://dx.doi.org/10.1007/s11332-015-0233-1]
[4]
Liu, C.; Huang, Y. Chinese herbal medicine on cardiovascular diseases and the mechanisms of action. Front. Pharmacol., 2016, 7, 469.
[http://dx.doi.org/10.3389/fphar.2016.00469] [PMID: 27990122]
[5]
Rousan, T.A.; Mathew, S.T.; Thadani, U. The risk of cardiovascular side effects with anti-anginal drugs. Expert Opin. Drug Saf., 2016, 15(12), 1609-1623.
[http://dx.doi.org/10.1080/14740338.2016.1238457] [PMID: 27659354]
[6]
Sarbacker, G.B.; Lusk, K.A.; Kalich, B. Aspirin for primary prevention of atherosclerotic cardiovascular disease in adults 80-years-of-age and older. Prog. Cardiovasc. Dis., 2018, 60(4-5), 562-564.
[http://dx.doi.org/10.1016/j.pcad.2017.12.006] [PMID: 29291428]
[7]
van Kruijsdijk, R.C.; Visseren, F.L.; Ridker, P.M.; Dorresteijn, J.A.; Buring, J.E.; van der Graaf, Y.; Cook, N.R. Individualised prediction of alternate-day aspirin treatment effects on the combined risk of cancer, cardiovascular disease and gastrointestinal bleeding in healthy women. Heart, 2015, 101(5), 369-376.
[http://dx.doi.org/10.1136/heartjnl-2014-306342] [PMID: 25475110]
[8]
Wang, Y.J.; Feng, S.H.; Cheng, J.T.; Chen, S. Research progress on chemical constituents and pharmacological action of anthraquinone in Rhei Radix et Rhizoma. Zhongguo Shiyan Fangjixue Zazhi, 2018, 24(13), 227-234.
[9]
Yu, J.; Liao, X.; Ding, H.; Yu, J.; Zhou, S. Research progress and clinical application of pharmacological effects of Chinese herbal rhubarb. Chin J Mod Drug, 2016, 10(11), 286-287.
[10]
Xiang, A.Y.; Wang, Y.; Yu, C.Q.; Liu, R.H. Two-way adjusting effects of rhubarb and its modern research basis. J Emerg Tradit Chin Med, 2016, 25(12), 2290-2291.
[11]
Liao, M.; Shang, H.; Li, Y.; Li, T.; Wang, M.; Zheng, Y.; Hou, W.; Liu, C. An integrated approach to uncover quality marker underlying the effects of Alisma orientale on lipid metabolism, using chemical analysis and network pharmacology. Phytomedicine, 2018, 45, 93-104.
[http://dx.doi.org/10.1016/j.phymed.2018.04.006] [PMID: 29705003]
[12]
Shen, X.; Zhao, Z.; Luo, X.; Wang, H.; Hu, B.; Guo, Z. Systems pharmacology based study of the molecular mechanism of SiNiSan formula for application in nervous and mental diseases. Evid. Based Complement. Alternat. Med., 2016, 20169146378
[http://dx.doi.org/10.1155/2016/9146378] [PMID: 28058059]
[13]
Shen, X.; Zhao, Z.; Wang, H.; Guo, Z.; Hu, B.; Zhang, G. Elucidation of the anti-inflammatory mechanisms of bupleuri and scutellariae radix using system pharmacological analyses. Mediators Inflamm., 2017, 20173709874
[http://dx.doi.org/10.1155/2017/3709874] [PMID: 28190938]
[14]
Zhang, Y.F.; Huang, Y.; Ni, Y.H.; Xu, Z.M. Systematic elucidation of the mechanism of geraniol via network pharmacology. Drug Des. Devel. Ther., 2019, 13, 1069-1075.
[http://dx.doi.org/10.2147/DDDT.S189088] [PMID: 31040644]
[15]
Gao, Y.; Gao, L.; Gao, X.X.; Zhou, Y.Z.; Qin, X.M.; Tian, J.S. An exploration in the action targets for antidepressant bioactive components of Xiaoyaosan based on network pharmacology. Yao Xue Xue Bao, 2015, 50(12), 1589-1595.
[PMID: 27169281]
[16]
Han, Y.Q.; Meng, F.C.; Xu, J.; Gong, S.X.; Zhang, T.J.; Liu, C.X. Study on compatibility rationality of Yuanhu Zhitong Dropping Pills for treatment of primary dysmenorrhea based on network pharmacology. Chin. Tradit. Herbal Drugs, 2017, 48(3), 526-532.
[17]
Cavasotto, C.N.; Abagyan, R.A. Protein flexibility in ligand docking and virtual screening to protein kinases. J. Mol. Biol., 2004, 337(1), 209-225.
[http://dx.doi.org/10.1016/j.jmb.2004.01.003] [PMID: 15001363]
[18]
Fu, X.S.; Chen, F.; Liu, X.H.; Xu, H.; Zhou, Y.Z. Progress in research of chemical constituents and pharmacological actions of Rhubarb.Chin J New Drugs, 2011, 20(16), 1534-1538+1568.
[19]
Gao, L.L. Studies on the chemical constituents and biological activity of Rheum tanguticum Maxim. ex Balf, Rheum officinale Bail and Rheum palmatum L.. PhD Thesis, Chinese Academy of Medical Sciences and Union Medical College School of Medicinal Plants: Beijing, . 2012.
[20]
Liu, Y.H.; Huang, Z.H.; Dong, L.; Pei, W.X.; Sun, Y.; Gao, X.Y. Simultaneous content determination of 14 components in Rhei Radix et Rhizoma by high performance liquid chromatography method.. Zhongguo Zhongyao Zazhi, 2017, 42(23), 4514-4519.
[PMID: 29376246]
[21]
Zhang, L. The source of rhubarb in rats based on HRMS Research on methods of sex component analysis.MD Thesis, Beijing University of Chinese Medicine: Beijing, 2015.
[22]
Zeng, F.; Li, Y. The active chemical constituents of rhubarb and their pharmacological action. Contemp Med, 2013, 19(12), 149-150.
[23]
Seo, E.J.; Ngoc, T.M.; Lee, S.M.; Kim, Y.S.; Jung, Y.S. Chrysophanol-8-O-glucoside, an anthraquinone derivative in rhubarb, has antiplatelet and anticoagulant activities. J. Pharmacol. Sci., 2012, 118(2), 245-254.
[http://dx.doi.org/10.1254/jphs.11123FP] [PMID: 22302018]
[24]
Tan, P.; Zhang, H.Z.; Li, Y. Preliminary study on antiplatelet aggregation of 10 anthraquinones in Rhei Radix et Rhizoma based on bioassay. Chin. Tradit. Herbal Drugs, 2018, 49(04), 859-865.
[25]
Liu, J.; Wang, L. Research progress of rhubarb. China Pharm, 2014, 25(25), 3351-3354.
[26]
Zhang, B.; Wang, B.; Wang, Y.Q.; Cao, S.H. Research progress on the protective effect of tannin in rhubarb on tissue damage. J. Emerg. Tradit. Chin. Med., 2015, 24(2), 286-287.
[27]
Tu, J. The mechanism of action of calcium antagonists in cardiovascular disease and its adverse reaction prevention measures. Chin. J. Clinical Rational Drug Use, 2017, 10(27), 120-122.
[28]
Li, Q.; Qin, M.; Tan, Q.; Li, T.; Gu, Z.; Huang, P.; Ren, L. MicroRNA-129-1-3p protects cardiomyocytes from pirarubicin-induced apoptosis by down-regulating the GRIN2D-mediated Ca signalling pathway. J. Cell. Mol. Med., 2020, 2020, 1-12.
[http://dx.doi.org/10.1111/jcmm.14908]
[29]
Mangge, H.; Becker, K.; Fuchs, D.; Gostner, J.M. Antioxidants, inflammation and cardiovascular disease. World J. Cardiol., 2014, 6(6), 462-477.
[http://dx.doi.org/10.4330/wjc.v6.i6.462] [PMID: 24976919]
[30]
Tan, X.H.; Zhang, D.S.; Zhang, L.; An, F.; Wang, S.H.; Jiang, H. Effects of rhubarb and its active components on cardiovascular system. Acta Neuropharm, 2005, 22(5), 68-69.
[31]
Shi, W.L.; Yuan, R.; Xin, Q.Q.; Jin, Y.; Cong, W.H.; Chen, K.J. Oxidative Stress and Hypertension. Med. Recapitulate, 2018, 24(4), 642-650.
[32]
Borissoff, J.I.; Spronk, H.M.; Heeneman, S.; ten Cate, H. Is thrombin a key player in the ‘coagulation-atherogenesis’ maze? Cardiovasc. Res., 2009, 82(3), 392-403.
[http://dx.doi.org/10.1093/cvr/cvp066] [PMID: 19228706]
[33]
Krishnaswamy, S. The transition of prothrombin to thrombin. J. Thromb. Haemost., 2013, 11(Suppl. 1), 265-276.
[http://dx.doi.org/10.1111/jth.12217] [PMID: 23809130]
[34]
Friedmann, A.P.; Koutychenko, A.; Wu, C.; Fredenburgh, J.C.; Weitz, J.I.; Gross, P.L.; Xu, P.; Ni, F.; Kim, P.Y. Identification and characterization of a factor Va-binding site on human prothrombin fragment 2. Sci. Rep., 2019, 9(1), 2436.
[http://dx.doi.org/10.1038/s41598-019-38857-4] [PMID: 30792421]
[35]
Zhou, C.L.; Ding, Z.J.; Cardiology, D.O. Prothrombin fragment 1+2 in cardiovascular disease. Med Recapitulate, 2014, 20(15), 2711-2713.
[36]
Mu, H.D.; Tu, P.F.; Jiang, Y. Network pharmacology-based study on mechanisms of warming channel and relieving stagnation effects of Cinnamomum cassia Presl. Yao Xue Xue Bao, 2016, 51(11), 1724-1733.
[PMID: 29908116]
[37]
Nustede, R.; Klimiankou, M.; Klimenkova, O.; Kuznetsova, I.; Zeidler, C.; Welte, K.; Skokowa, J. ELANE mutant-specific activation of different UPR pathways in congenital neutropenia. Br. J. Haematol., 2016, 172(2), 219-227.
[http://dx.doi.org/10.1111/bjh.13823] [PMID: 26567890]
[38]
Zhao, C.; Wu, Y. Advances in research of calcium signals and cardiovascular diseases in cardiomyocytes. J Pract Med, 2017, 33(3), 492-495.
[39]
Yu, Z.H.; Cai, M.; Xiang, J.; Zhang, Z.N.; Zhang, J.S.; Song, X.L.; Zhang, W.; Bao, J.; Li, W.W.; Cai, D.F. PI3K/Akt pathway contributes to neuroprotective effect of Tongxinluo against focal cerebral ischemia and reperfusion injury in rats. J. Ethnopharmacol., 2016, 181, 8-19.
[http://dx.doi.org/10.1016/j.jep.2016.01.028] [PMID: 26805466]
[40]
Kofler, N.M.; Simons, M. Angiogenesis versus arteriogenesis: neuropilin 1 modulation of VEGF signaling. F1000Prime Rep., 2015, 7, 26.
[http://dx.doi.org/10.12703/P7-26] [PMID: 25926977]
[41]
Lee, S.; Chen, T.T.; Barber, C.L.; Jordan, M.C.; Murdock, J.; Desai, S.; Ferrara, N.; Nagy, A.; Roos, K.P.; Iruela-Arispe, M.L. Autocrine VEGF signaling is required for vascular homeostasis. Cell, 2007, 130(4), 691-703.
[http://dx.doi.org/10.1016/j.cell.2007.06.054] [PMID: 17719546]
[42]
Rincon, M.Y.; VandenDriessche, T.; Chuah, M.K. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation. Cardiovasc. Res., 2015, 108(1), 4-20.
[http://dx.doi.org/10.1093/cvr/cvv205] [PMID: 26239654]
[43]
Wang, H.; Li, Y.; Shi, G.; Wang, Y.; Lin, Y.; Wang, Q.; Zhang, Y.; Yang, Q.; Dai, L.; Cheng, L.; Su, X.; Yang, Y.; Zhang, S.; Li, Z.; Li, J.; Wei, Y.; Yu, D.; Deng, H. A Novel Antitumor Strategy: Simultaneously Inhibiting Angiogenesis and Complement by Targeting VEGFA/PIGF and C3b/C4b. Mol. Ther. Oncolytics, 2019, 16, 20-29.
[http://dx.doi.org/10.1016/j.omto.2019.12.004] [PMID: 31909182]
[44]
McManus, D.D.; Freedman, J.E. MicroRNAs in platelet function and cardiovascular disease. Nat. Rev. Cardiol., 2015, 12(12), 711-717.
[http://dx.doi.org/10.1038/nrcardio.2015.101] [PMID: 26149483]
[45]
Wang, J.; Cheng, J.; Zhang, C.; Li, X. Cardioprotection effects of sevoflurane by regulating the pathway of neuroactive ligand-receptor interaction in patients undergoing coronary artery bypass graft surgery. Comput. Math. Methods Med., 2017, 20173618213
[http://dx.doi.org/10.1155/2017/3618213] [PMID: 28348638]
[46]
Dunkelberger, J.R.; Song, W.C. Complement and its role in innate and adaptive immune responses. Cell Res., 2010, 20(1), 34-50.
[http://dx.doi.org/10.1038/cr.2009.139] [PMID: 20010915]
[47]
Ahn, S.M.; Kim, H.N.; Kim, Y.R.; Choi, Y.W.; Kim, C.M.; Shin, H.K.; Choi, B.T. Emodin from Polygonum multiflorum ameliorates oxidative toxicity in HT22 cells and deficits in photothrombotic ischemia. J. Ethnopharmacol., 2016, 188, 13-20.
[48]
Kou, R. The pharmacological study of treating cardiovascular diseases with Rhubarb. Zhonghua Zhongyiyao Xuekan, 2003, 21(10), 1692-1693.
[49]
Xue, H.W.; Zhou, C.F. Bidirectional regulation of materia medica and its clinical application. SH J TCM, 2010, 44(10), 16-17.
[50]
Qin, L.S.; Zhao, H.P.; Zhao, Y.L; Ma, Z.J.; Zeng, L.N.; Zhang, Y.M; Zhang, P.; Yan, D.; Bai, Z.F.; Li, Y.; Hao, Q.X; Zhao, K.J.; Wang, J.B.; Xiao, X.H. Protection and bidirectional effect of rhubarb anthraquinone and tannins for rats’ liver. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2014, 34(6), 698-703.
[PMID: 25046953]

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