Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

Network Pharmacology Analysis of the Effects of Achyranthis Bidentatae Radix Plus Semen Vaccariae on Migraine-induced Erectile Dysfunction

Author(s): Jisheng Wang, Junlong Feng, Sheng Deng, Binghao Bao, Fanchao Meng, Hengheng Dai, Hongsheng Xu, Shizhen Wang, Bin Wang * and Haisong Li*

Volume 25, Issue 9, 2022

Published on: 05 January, 2022

Page: [1474 - 1487] Pages: 14

DOI: 10.2174/1386207324666210628105233

Price: $65

Abstract

Background and Aim: Achyranthis Bidentatae Radix plus Semen Vaccariae are traditional Chinese medicines, which have been widely applied in the treatment of migraine and Erectile Dysfunction (ED) for many years. This study verified the effect of Achyranthis Bidentatae Radix plus Semen Vaccariae in improving migraine-induced ED and explored its potential mechanism.

Methods: Key targets and signaling pathways of Achyranthis Bidentatae Radix plus Semen Vaccariae in migraine-induced erectile dysfunction treatment were predicted by network pharmacology. A rat model of migraine was established by nitroglycerin injection. Apomorphine was injected into rats to screen the migraine-induced erectile dysfunction model, Achyranthis Bidentatae Radix-Semen Vaccariae granule suspension administered, and erectile function evaluated. Hematoxylin and eosin staining was used to compare the histological structure of the penile tissue, while RT-qPCR and Western blotting were used to determine mRNA and protein levels, respectively.

Results: Screening allowed us to identify common targets for migraine and ED; the signaling pathway exhibiting the greatest change was the Myosin light chain kinase- Calcium (MLCK-CaM) signal pathway. From Western blotting and RT-qPCR, we found that the levels of MLCK mRNA and protein in rats from Group B rats were significantly higher (P <0.05) than those in Groups A and C. Furthermore, the mRNA and protein levels of CaM were significantly higher in Group B (P <0.05) than in Groups A and C.

Conclusion: Data indicate that the regulatory effects of Achyranthis Bidentatae Radix plus Semen Vaccariae on migraine-induced ED in a rat model are mediated by the MLCK-CaM signaling pathway.

Keywords: Achyranthis bidentatae radix, semen vaccariae, migraine, erectile dysfunction, MLCK-CaM signaling pathway, rat model.

Graphical Abstract

[1]
Arnold, M. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders. Cephalalgia; 3rd, 2018, 38, 1-211.
[2]
Silberstein, S.D. Migraine. Lancet, 2004, 363(9406), 381-391.
[http://dx.doi.org/10.1016/S0140-6736(04)15440-8] [PMID: 15070571]
[3]
The international classification of headache disorders. Cephalalgia, 3rd;, 2013, 33(9), 629-808.
[4]
Diener, H.C. The risks or lack thereof of migraine treatments in vascular disease. Headache, 2020, 60(3), 649-653.
[http://dx.doi.org/10.1111/head.13749] [PMID: 31967337]
[5]
Cardia, L.; Calapai, F.; Mondello, C.; Quattrone, D.; Elisa Sorbara, E.; Mannucci, C.; Calapai, G.; Mondello, E. Clinical use of omega-3 fatty acids in migraine: A narrative review. Medicine (Baltimore), 2020, 99(42), e22253.
[http://dx.doi.org/10.1097/MD.0000000000022253] [PMID: 33080672]
[6]
Burnett, A.L.; Nehra, A.; Breau, R.H.; Culkin, D.J.; Faraday, M.M.; Hakim, L.S.; Heidelbaugh, J.; Khera, M.; McVary, K.T.; Miner, M.M.; Nelson, C.J.; Sadeghi-Nejad, H.; Seftel, A.D.; Shindel, A.W. Erectile dysfunction: AUA guideline. J. Urol., 2018, 200(3), 633-641.
[http://dx.doi.org/10.1016/j.juro.2018.05.004] [PMID: 29746858]
[7]
Huang, C.Y.; Keller, J.J.; Sheu, J.J.; Lin, H.C. Migraine and erectile dysfunction: Evidence from a population-based case-control study. Cephalalgia, 2012, 32(5), 366-372.
[http://dx.doi.org/10.1177/0333102412439801] [PMID: 22407657]
[8]
Wu, S.H.; Chuang, E.; Chuang, T.Y.; Lin, C.L.; Lin, M.C.; Yen, D.J.; Kao, C.H. A nationwide population-based cohort study of migraine and organic-psychogenic erectile dysfunction. Medicine (Baltimore), 2016, 95(10), e3065.
[http://dx.doi.org/10.1097/MD.0000000000003065] [PMID: 26962838]
[9]
Nemichandra, S.C.; Pradeep, R.; Harsha, S.; Radhika, K.; Iqbal, R. Erectile dysfunction in migraine in Indian patients. Ann. Indian Acad. Neurol., 2020, 23(6), 792-795.
[http://dx.doi.org/10.4103/aian.AIAN_554_19] [PMID: 33688129]
[10]
Edvinsson, L.; Haanes, K.A.; Warfvinge, K. Does inflammation have a role in migraine? Nat. Rev. Neurol., 2019, 15(8), 483-490.
[http://dx.doi.org/10.1038/s41582-019-0216-y] [PMID: 31263254]
[11]
Ashina, M.; Hansen, J.M.; Do, T.P.; Melo-Carrillo, A.; Burstein, R.; Moskowitz, M.A. Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol., 2019, 18(8), 795-804.
[http://dx.doi.org/10.1016/S1474-4422(19)30185-1] [PMID: 31160203]
[12]
Wei, Z.; Li, M.; Zhang, Y. Clinical research progress of traditional chinese medicine in the treatment of migraine. Chinese J. Cardio Cerebrovascular Dis., 2020, 18(17), 2804-2809.
[13]
Ji, Y.; Ling, J.; Pang, L. Interstitial cells of Cajal, Ca~(2+) and gastrointestinal motility. J. Practical Med., 2013, 29(11), 1872-1873.
[14]
Ma, T.; Qi, Q.H.; Xu, J.; Dong, Z.L.; Yang, W.X. Signal pathways involved in emodin-induced contraction of smooth muscle cells from rat colon. World J. Gastroenterol., 2004, 10(10), 1476-1479.
[http://dx.doi.org/10.3748/wjg.v10.i10.1476] [PMID: 15133857]
[15]
Manoury, B.; Idres, S.; Leblais, V.; Fischmeister, R. Ion channels as effectors of cyclic nucleotide pathways: Functional relevance for arterial tone regulation. Pharmacol. Ther., 2020, 209, 107499.
[http://dx.doi.org/10.1016/j.pharmthera.2020.107499] [PMID: 32068004]
[16]
Zhang, C.; Wan, Q. Mechanism of 5-HT1D receptor regulating CGRP expression and release in trigeminal sensory neurons. Chinese J. Pain Med., 2015, 21(03), 213-216.
[17]
Vámos, E.; Fejes, A.; Koch, J.; Tajti, J.; Fülöp, F.; Toldi, J.; Párdutz, A.; Vécsei, L. Kynurenate derivative attenuates the nitroglycerin-induced CamKIIα and CGRP expression changes. Headache, 2010, 50(5), 834-843.
[http://dx.doi.org/10.1111/j.1526-4610.2009.01574.x] [PMID: 19925620]
[18]
Hackett, G.; Cole, N.; Mulay, A.; Strange, R.C.; Ramachandran, S. Long-term testosterone therapy in type 2 diabetes is associated with decreasing waist circumference and improving erectile function. World J. Mens Health, 2020, 38(1), 68-77.
[http://dx.doi.org/10.5534/wjmh.180052M] [PMID: 30209900]
[19]
Zhang, L. Mechanism study on the intervention of tonifying kidney qi method on sex hormone level and sex hormone receptor expression in elderly hypertensive patients with kidney qi deficiency syndrome; Shandong Univ Tradi Chin Med, 2012.
[20]
Yang, K. Zeng Qingqi’s academic thought on the treatment of male infertility and the clinical and experimental study of runjing Decoction in the treatment of oligoasthenospermia; Nanjing Univ Tradi Chin Med, 2020.
[21]
Chen, W.; Gong, L.; Guo, Z.; Wang, W.; Zhang, H.; Liu, X.; Yu, S.; Xiong, L.; Luo, J. A novel integrated method for large-scale detection, identification, and quantification of widely targeted metabolites: Application in the study of rice metabolomics. Mol. Plant, 2013, 6(6), 1769-1780.
[http://dx.doi.org/10.1093/mp/sst080] [PMID: 23702596]
[22]
Garcia, A.; Barbas, C. Gas chromatography-mass spectrometry (GC-MS)-based metabolomics. Methods Mol. Biol., 2011, 708, 191-204.
[http://dx.doi.org/10.1007/978-1-61737-985-7_11] [PMID: 21207291]
[23]
Ma, T.T.; Zhang, G.L.; Dai, C.F.; Zhang, B.R.; Cao, K.X.; Wang, C.G.; Yang, G.W.; Wang, X.M. Scutellaria barbata and Hedyotis diffusa herb pair for breast cancer treatment: Potential mechanism based on network pharmacology. J. Ethnopharmacol., 2020, 259, 112929.
[http://dx.doi.org/10.1016/j.jep.2020.112929] [PMID: 32416245]
[24]
Rappaport, N.; Fishilevich, S.; Nudel, R.; Twik, M.; Belinky, F.; Plaschkes, I.; Stein, T.I.; Cohen, D.; Oz-Levi, D.; Safran, M.; Lancet, D. Rational confederation of genes and diseases: NGS interpretation via genecards, malacards and varelect. Biomed. Eng. Online, 2017, 16(Suppl. 1), 72.
[http://dx.doi.org/10.1186/s12938-017-0359-2] [PMID: 28830434]
[25]
Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res., 2017, 45(D1), D362-D368.
[http://dx.doi.org/10.1093/nar/gkw937] [PMID: 27924014]
[26]
Hao, C.; Xiao, P.G. Network pharmacology: A rosetta stone for traditional chinese medicine. Drug Dev. Res., 2014, 75(5), 299-312.
[http://dx.doi.org/10.1002/ddr.21214] [PMID: 25160070]
[27]
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[28]
Tao, W.; Xu, X.; Wang, X.; Li, B.; Wang, Y.; Li, Y.; Yang, L. Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease. J. Ethnopharmacol., 2013, 145(1), 1-10.
[http://dx.doi.org/10.1016/j.jep.2012.09.051] [PMID: 23142198]
[29]
Huang, W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[30]
Sidders, B.; Karlsson, A.; Kitching, L.; Torella, R.; Karila, P.; Phelan, A. Network-based drug discovery: Coupling network pharmacology with phenotypic screening for neuronal excitability. J. Mol. Biol., 2018, 430(18 Pt A), 3005-3015.
[http://dx.doi.org/10.1016/j.jmb.2018.07.016] [PMID: 30030026]
[31]
Long, P.; Yan, W.; Liu, J.; Li, M.; Chen, T.; Zhang, Z.; An, J. Therapeutic effect of traditional chinese medicine on a rat model of branch retinal vein occlusion. J. Ophthalmol., 2019, 2019(7), 9521379.
[http://dx.doi.org/10.1155/2019/9521379] [PMID: 30906588]
[32]
Itoga, A.; Zha, X.; Nagase, K.; Aoki, Y.; Ito, H.; Yokoyama, O. Correcting imbalance of sex hormones by a phosphodiesterase 5 inhibitor improves copulatory dysfunction in male rats with type 2 diabetes. BMJ Open Diabetes Res. Care, 2020, 8(1), e001111.
[http://dx.doi.org/10.1136/bmjdrc-2019-001111] [PMID: 32371530]
[33]
Li, Y.; Zhang, Q.; Qi, D.; Zhang, L.; Yi, L.; Li, Q.; Zhang, Z. Valproate ameliorates nitroglycerin-induced migraine in trigeminal nucleus caudalis in rats through inhibition of NF-кB. B. J. Headache Pain, 2016, 17, 49.
[http://dx.doi.org/10.1186/s10194-016-0631-z] [PMID: 27150105]
[34]
Heaton, J.P.; Varrin, S.J.; Morales, A. The characterization of a bio-assay of erectile function in a rat model. J. Urol., 1991, 145(5), 1099-1102.
[http://dx.doi.org/10.1016/S0022-5347(17)38543-9] [PMID: 2016801]
[35]
Park, J.; Chai, J.S.; Kim, S.W.; Paick, J.S.; Cho, M.C. Inhibition of Jun N-terminal kinase improves erectile function by alleviation of cavernosal apoptosis in a rat model of cavernous nerve injury. Urology, 2018, 113, 253.e9-253.e16.
[http://dx.doi.org/10.1016/j.urology.2017.11.040] [PMID: 29203189]
[36]
Appleton, C.T.; McErlain, D.D.; Henry, J.L.; Holdsworth, D.W.; Beier, F. Molecular and histological analysis of a new rat model of experimental knee osteoarthritis. Ann. N. Y. Acad. Sci., 2007, 1117, 165-174.
[http://dx.doi.org/10.1196/annals.1402.022] [PMID: 17646269]
[37]
Huang, Y. T.; van der Hoorn, D.; Ledahawsky, L. M.; Motyl, A. A. L.; Jordan, C. Y.; Gillingwater, T. H.; Groen, E. J. N. Robust comparison of protein levels across tissues and throughout development using standardized quantitative western blotting. J Vis Exp, 2019, 146
[http://dx.doi.org/10.3791/59438]
[38]
Hong, K.M.; Najjar, H.; Hawley, M.; Press, R.D. Quantitative real-time PCR with automated sample preparation for diagnosis and monitoring of cytomegalovirus infection in bone marrow transplant patients. Clin. Chem., 2004, 50(5), 846-856.
[http://dx.doi.org/10.1373/clinchem.2003.026484]
[39]
Steiner, T.J.; Stovner, L.J.; Birbeck, G.L. Migraine: The seventh disabler. Cephalalgia, 2013, 33(5), 289-290.
[http://dx.doi.org/10.1177/0333102412473843] [PMID: 23307815]
[40]
Martelletti, P.; Schwedt, T.J.; Lanteri-Minet, M.; Quintana, R.; Carboni, V.; Diener, H.C.; Ruiz de la Torre, E.; Craven, A.; Rasmussen, A.V.; Evans, S.; Laflamme, A.K.; Fink, R.; Walsh, D.; Dumas, P.; Vo, P. My migraine voice survey: A global study of disease burden among individuals with migraine for whom preventive treatments have failed. J. Headache Pain, 2018, 19(1), 115.
[http://dx.doi.org/10.1186/s10194-018-0946-z] [PMID: 30482181]
[41]
Deng, L.; Liu, W.; Zhao, Y. Clinical application progress of achyranthes bidentata in the treatment of hypertension. Liaoning. J. Tradit. Chin. Med., 2020, 47(01), 195-197.
[42]
Fu, Q.; Miao, Q.; Zhang, Y. Clinical application research progress of Wang buliuxing. Chinese medicine information, 2016, 33(05), 117-121.
[43]
Martinsen, A.; Dessy, C.; Morel, N. Regulation of calcium channels in smooth muscle: New insights into the role of myosin light chain kinase. Channels (Austin), 2014, 8(5), 402-413.
[http://dx.doi.org/10.4161/19336950.2014.950537] [PMID: 25483583]
[44]
Sanders, K.M.; Koh, S.D.; Ro, S.; Ward, S.M. Regulation of gastrointestinal motility-insights from smooth muscle biology. Nat. Rev. Gastroenterol. Hepatol., 2012, 9(11), 633-645.
[http://dx.doi.org/10.1038/nrgastro.2012.168] [PMID: 22965426]
[45]
He, W.Q.; Peng, Y.J.; Zhang, W.C.; Lv, N.; Tang, J.; Chen, C.; Zhang, C.H.; Gao, S.; Chen, H.Q.; Zhi, G.; Feil, R.; Kamm, K.E.; Stull, J.T.; Gao, X.; Zhu, M.S. Myosin light chain kinase is central to smooth muscle contraction and required for gastrointestinal motility in mice. Gastroenterology, 2008, 135(2), 610-620.
[http://dx.doi.org/10.1053/j.gastro.2008.05.032] [PMID: 18586037]
[46]
Brevern, M. V.; Lempert, T. Vestibular migraine: Treatment and prognosis. Semin Neurol, 2020, 40(01), 083-086.
[47]
Yafi, F.A.; Jenkins, L.; Albersen, M.; Corona, G.; Isidori, A.M.; Goldfarb, S.; Maggi, M.; Nelson, C.J.; Parish, S.; Salonia, A.; Tan, R.; Mulhall, J.P.; Hellstrom, W.J. Erectile dysfunction. Nat. Rev. Dis. Primers, 2016, 2, 16003.
[http://dx.doi.org/10.1038/nrdp.2016.3] [PMID: 27188339]
[48]
Cao, Y.; Gu, C.; Zhao, F.; Tang, Y.; Cui, X.; Shi, L.; Xu, L.; Yin, L. Therapeutic Effects of Cyathula officinalis Kuan and Its Active Fraction on Acute Blood Stasis Rat Model and Identification Constituents by HPLC-QTOF/MS/MS. Pharmacogn. Mag., 2017, 13(52), 693-701.
[http://dx.doi.org/10.4103/pm.pm_560_16] [PMID: 29200735]
[49]
Zhang, T.; Niu, C.; Qin, X. Effect of Wang buliuxing on tension of rabbit aortic rings in vitro and its mechanism. Pharmacol. Clinic Taditi Chin. Med., 2004, (04), 28-29.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy