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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Combinatorial Chemistry &amp; High Throughput Screening</journal-id><journal-title-group><journal-title xml:lang="en">Combinatorial Chemistry &amp; High Throughput Screening</journal-title><trans-title-group xml:lang="ru"><trans-title>Combinatorial Chemistry &amp; High Throughput Screening</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1386-2073</issn><issn publication-format="electronic">1875-5402</issn><publisher><publisher-name xml:lang="en">Bentham Science</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">644569</article-id><article-id pub-id-type="doi">10.2174/0113862073264485240102064653</article-id><article-categories><subj-group subj-group-type="toc-heading"><subject>Chemistry</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Investigation of the Potential Mechanism of Compound Dragon's Blood Capsule against Myocardial Ischemia Based on Network Pharmacology</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Su</surname><given-names>Xin</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name><surname>Xue</surname><given-names>Hongwei</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name><surname>Lou</surname><given-names>Yang</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><name><surname>Lv</surname><given-names>Xinkai</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name><surname>Mi</surname><given-names>Xiao</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name><surname>Lu</surname><given-names>Juan</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Xi</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff3"/></contrib></contrib-group><aff id="aff1"><institution>Chinese Academy of Medical Sciences, Yunnan Branch, Institute of Medicinal Plant Development</institution></aff><aff id="aff2"><institution>Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College</institution></aff><aff id="aff3"><institution>Chinese Academy of Medical Sciences, Peking Union Medical College, Institute of Medicinal Plant Development</institution></aff><pub-date date-type="pub" iso-8601-date="2024-10-01" publication-format="electronic"><day>01</day><month>10</month><year>2024</year></pub-date><volume>27</volume><issue>19</issue><issue-title xml:lang="ru"/><fpage>2940</fpage><lpage>2950</lpage><history><date date-type="received" iso-8601-date="2025-01-07"><day>07</day><month>01</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Bentham Science Publishers</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Bentham Science Publishers</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/></permissions><self-uri xlink:href="https://rjpbr.com/1386-2073/article/view/644569">https://rjpbr.com/1386-2073/article/view/644569</self-uri><abstract xml:lang="en"><p id="idm46041443777712">Background:Dragon's blood is widely consumed in China, Vietnam and Laos to promote blood circulation. A Compound Dragon's blood capsule (CDC) is a patented medicine composed of dragons blood, notoginseng, and borneol. This combination is purported to stabilize coronary heart disease and myocardial ischemia. However, the possible mechanisms and the characterization of its drug targets relevance at the systemic level remain unclear.</p><p id="idm46041443781712">Aim:The present study aims to reveal the potential mechanisms of CDCs anti-myocardial ischemia effect</p><p id="idm46041443785680">Materials and Methods:The potential mechanisms were investigated by network pharmacology and qRT-PCR was used to verify the expression levels of key genes of PI3k-Akt pathway.</p><p id="idm46041443790736">Results:S1PR2 and AGTR1 were the common targets, which involved 6 biological processes annotated by KEGG and GO analysis. The qRT-PCR results showed a remarkable increase in the expression of Pi3k, Pdk1, Akt, Mdm2, Bcl2, and mTOR. Results also showed a decline in the expression of P53 and Casp3 after CDC intervention.</p><p id="idm46041443800112">Conclusion:CDC has a significant anti-myocardial ischemia effect through the PI3k/Akt pathway, which demonstrates that CDC is a suitable adjuvant to treat CHD and provides a theoretical basis for its further clinical application.</p></abstract><kwd-group xml:lang="en"><kwd>Compound dragon's blood capsule</kwd><kwd>myocardial ischemia</kwd><kwd>network pharmacology</kwd><kwd>Pi3k-akt pathway</kwd><kwd>ROS</kwd><kwd>mTOR.</kwd></kwd-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Zhao, D.; Liu, J.; Wang, M.; Zhang, X.; Zhou, M. Epidemiology of cardiovascular disease in China: Current features and implications. Nat. Rev. Cardiol., 2019, 16(4), 203-212. doi: 10.1038/s41569-018-0119-4 PMID: 30467329</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Boyle, S.H.; Samad, Z.; Becker, R.C.; Williams, R.; Kuhn, C.; Ortel, T.L.; Kuchibhatla, M.; Prybol, K.; Rogers, J.; OConnor, C.; Velazquez, E.J.; Jiang, W. Depressive symptoms and mental stress-induced myocardial ischemia in patients with coronary heart disease. Psychosom. Med., 2013, 75(9), 822-831. doi: 10.1097/PSY.0b013e3182a893ae PMID: 24163385</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Wang, Y.; Zhang, Z.Z.; Wu, Y.; Zhan, J.; He, X.H.; Wang, Y.L. Honokiol protects rat hearts against myocardial ischemia reperfusion injury by reducing oxidative stress and inflammation. Exp. Ther. Med., 2013, 5(1), 315-319. doi: 10.3892/etm.2012.766 PMID: 23251290</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Suchal, K.; Malik, S.; Gamad, N.; Malhotra, R.K.; Goyal, S.N.; Chaudhary, U.; Bhatia, J.; Ojha, S.; Arya, D.S. Kaempferol attenuates myocardial ischemic injury via inhibition of MAPK signaling pathway in experimental model of myocardial ischemia-reperfusion injury. Oxid. Med. Cell. Longev., 2016, 2016, 1-10. doi: 10.1155/2016/7580731 PMID: 27087891</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Riazuddin, S.; Husnain, T.; Malik, T.; Farooqi, H.; Abbar, S.T. Establishment of callus-tissue culture and the induction of organogenesis in chickpea. Cancer Treat. Rev., 1988, 29(5), 407-415.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Su, D.; Zhou, Y.; Hu, S.; Guan, L.; Shi, C.; Wang, Q.; Chen, Y.; Lu, C.; Li, Q.; Ma, X. Role of GAB1/PI3K/AKT signaling high glucose-induced cardiomyocyte apoptosis. Biomed. Pharmacother., 2017, 93, 1197-1204. doi: 10.1016/j.biopha.2017.07.063 PMID: 28738535</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Feng, F.B.; Qiu, H.Y. RETRACTED: Effects of artesunate on chondrocyte proliferation, apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway in rat models with rheumatoid arthritis. Biomed. Pharmacother., 2018, 102, 1209-1220. doi: 10.1016/j.biopha.2018.03.142 PMID: 29710540</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Okada, T.; Enkhjargal, B.; Travis, Z.D.; Ocak, U.; Tang, J.; Suzuki, H.; Zhang, J.H. FGF-2 Attenuates Neuronal Apoptosis via FGFR3/PI3k/Akt Signaling Pathway After Subarachnoid Hemorrhage. Mol. Neurobiol., 2019, 56(12), 8203-8219. doi: 10.1007/s12035-019-01668-9 PMID: 31203572</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Dvir, D.; Battler, A. Conventional and novel drug therapeutics to relief myocardial ischemia. Cardiovasc. Drugs Ther., 2010, 24(4), 319-323. doi: 10.1007/s10557-010-6254-8 PMID: 20658184</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Wan, X.; Meng, J.; Dai, Y.; Zhang, Y.; Yan, S. Visualization of network target crosstalk optimizes drug synergism in myocardial ischemia. PLoS One, 2014, 9(2), e88137. doi: 10.1371/journal.pone.0088137 PMID: 24505402</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Min, Li. Potential effectiveness of chinese patent medicine tongxinluo capsule for secondary prevention after acute myocardial infarction: A systematic review and meta-analysis of randomized controlled trials. Front. Pharmacol., 2018, 9, 830.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Liu, F.; Huang, Z.Z.; Sun, Y.H.; Li, T.; Yang, D.H.; Xu, G.; Su, Y.Y.; Zhang, T. Four main active ingredients derived from a traditional chinese medicine guanxin shutong capsule cause cardioprotection during myocardial ischemia injury calcium overload suppression. Phytother. Res., 2017, 31(3), 507-515. doi: 10.1002/ptr.5787 PMID: 28164397</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Yin, H.; Zhang, J.; Lin, H.; Qiao, Y.; Wang, R.; Lu, H.; Liang, S. Effect of traditional Chinese medicine Shu‐mai‐tang on angiogenesis, arteriogenesis and cardiac function in rats with myocardial ischemia. Phytother. Res., 2009, 23(1), 92-98. doi: 10.1002/ptr.2565 PMID: 18814204</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Zhao, L.; Zhang, H.; Li, N.; Chen, J.; Xu, H.; Wang, Y.; Liang, Q. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula. J. Ethnopharmacol., 2023, 309, 116306. doi: 10.1016/j.jep.2023.116306 PMID: 36858276</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Niu, B.; Zhang, H.; Li, C.; Yan, F.; Song, Y.; Hai, G.; Jiao, Y.; Feng, Y. Network pharmacology study on the active components of Pterocypsela elata and the mechanism of their effect against cerebral ischemia. Drug Des. Devel. Ther., 2019, 13, 3009-3019. doi: 10.2147/DDDT.S207955 PMID: 31564827</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Liu, A.L.; Du, G.H. Network pharmacology: New guidelines for drug discovery. Acta Pharmacol. Sin., 2010, 45(12), 1472-1477.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Lyu, X.K.; Chang, X.Y.; Mi, X.; Hu, M.G.; Yu, Y.; Wang, J.C.; Hu, S.M.; Chen, X.; Li, Y.H.; Lu, J. Compound Dragons blood capsule alleviates the degree of myocardial ischemia by improving inflammation and oxidative stress Res. Squa., 2022, 2022, 1086482. doi: 10.21203/rs.3.rs-1086482/v1</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Cui, Z.; Gu, L.; Liu, T.; Liu, Y.; Yu, B.; Kou, J.; Li, F.; Yang, K. Ginsenoside Rd attenuates myocardial ischemia injury through improving mitochondrial biogenesis via WNT5A/Ca2+ pathways. Eur. J. Pharmacol., 2023, 957, 176044. doi: 10.1016/j.ejphar.2023.176044 PMID: 37660968</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Qin, G.W.; Lu, P.; Peng, L.; Jiang, W. Ginsenoside Rb1 inhibits cardiomyocyte autophagy via PI3K/Akt/mTOR signaling pathway and reduces myocardial ischemia/reperfusion injury. Am. J. Chin. Med., 2021, 49(8), 1913-1927. doi: 10.1142/S0192415X21500907 PMID: 34775933</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Li, Q.; Yuan, M.; Li, X.; Li, J.; Xu, M.; Wei, D.; Wu, D.; Wan, J.; Mei, S.; Cui, T.; Wang, J.; Zhu, Z. New dammarane-type triterpenoid saponins from Panax notoginseng saponins. J. Ginseng Res., 2020, 44(5), 673-679. doi: 10.1016/j.jgr.2018.12.001 PMID: 32913396</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Ramli, F.F.; Ali, A.; Ibrahim, N.I. Molecular-signaling pathways of ginsenosides Rb in myocardial ischemia-reperfusion injury: A mini review. Int. J. Med. Sci., 2022, 19(1), 65-73. doi: 10.7150/ijms.64984 PMID: 34975299</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Xing, X.; Guo, S.; Zhang, G.; Liu, Y.; Bi, S.; Wang, X.; Lu, Q. miR-26a-5p protects against myocardial ischemia/reperfusion injury by regulating the PTEN/PI3K/AKT signaling pathway. Braz. J. Med. Biol. Res., 2020, 53(2), e9106. doi: 10.1590/1414-431x20199106 PMID: 31994603</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Xiangyan, Li. Compound K inhibits autophagy-mediated apoptosis through activation of the PI3K-Akt signaling pathway thus protecting against ischemia/reperfusion injury. Cell. Physiol. Biochem., 2018, 476, 2589-2601.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Zhang, X.; Chen, B.; Wu, J.; Sha, J.; Yang, B.; Zhu, J.; Sun, J.; Hartung, J.; Bao, E. Aspirin enhances the protection of Hsp90 from heat-stressed injury in cardiac microvascular endothelial cells through PI3K-Akt and PKM2 pathways. Cells, 2020, 9(1), 243. doi: 10.3390/cells9010243 PMID: 31963688</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Liu, M.; Yang, P.; Fu, D.; Gao, T.; Deng, X.; Shao, M.; Liao, J.; Jiang, H.; Li, X. Allicin protects against myocardial I/R by accelerating angiogenesis via the miR-19a-3p/PI3K/AKT axis. Aging, 2021, 13(19), 22843-22855. doi: 10.18632/aging.203578 PMID: 34607973</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Chen, X.; Zhabyeyev, P.; Azad, A.K.; Wang, W.; Minerath, R.A.; Desaulniers, J.; Grueter, C.E.; Murray, A.G.; Kassiri, Z.; Vanhaesebroeck, B. Endothelial and cardiomyocyte PI3Kβ divergently regulate cardiac remodelling in response to ischaemic injury. Cardiovasc. Res., 2019, 115(8), 1343-1356.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Liu, J.; Fan, C.; Yu, L.; Yang, Y.; Jiang, S.; Ma, Z.; Hu, W.; Li, T.; Yang, Z.; Tian, T.; Duan, W.; Yu, S. Pterostilbene exerts an anti-inflammatory effect via regulating endoplasmic reticulum stress in endothelial cells. Cytokine, 2016, 77, 88-97. doi: 10.1016/j.cyto.2015.11.006 PMID: 26551859</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Tedgui, A.; Mallat, Z. Inflammation and atherosclerosis. Nephrologie, 2003, 24(7), 411-414. PMID: 14650755</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Jeong, C.W.; Yoo, K.Y.; Lee, S.H.; Jeong, H.J.; Lee, C.S.; Kim, S.J. Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3β and inhibition of p38 MAPK and JNK. J. Cardiovasc. Pharmacol. Ther., 2012, 17(4), 387-394. doi: 10.1177/1074248412438102 PMID: 22396328</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Dong, L.Y.; Li, S.; Zhen, Y.L.; Wang, Y.N.; Shao, X.; Luo, Z.G. Cardioprotection of vitexin on myocardial ischemia/reperfusion injury in rat via regulating inflammatory cytokines and MAPK pathway. Am. J. Chin. Med., 2013, 41(6), 1251-1266. doi: 10.1142/S0192415X13500845 PMID: 24228599</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Blaustein, M.P.; Lederer, W.J. Sodium/calcium exchange: Its physiological implications. Physiol. Rev., 1999, 79(3), 763-854. doi: 10.1152/physrev.1999.79.3.763 PMID: 10390518</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Der Sarkissian, S.; Huentelman, M.J.; Stewart, J.; Katovich, M.J.; Raizada, M.K. ACE2: A novel therapeutic target for cardiovascular diseases. Prog. Biophys. Mol. Biol., 2006, 91(1-2), 163-198. doi: 10.1016/j.pbiomolbio.2005.05.011 PMID: 16009403</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Fernández-Hernando, C.; Ackah, E.; Yu, J.; Suárez, Y.; Murata, T.; Iwakiri, Y.; Prendergast, J.; Miao, R.Q.; Birnbaum, M.J.; Sessa, W.C. Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Cell Metab., 2007, 6(6), 446-457. doi: 10.1016/j.cmet.2007.10.007 PMID: 18054314</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Ackah, E.; Yu, J.; Zoellner, S.; Iwakiri, Y.; Skurk, C.; Shibata, R.; Ouchi, N.; Easton, R.M.; Galasso, G.; Birnbaum, M.J.; Walsh, K.; Sessa, W.C. Akt1/protein kinase B is critical for ischemic and VEGF-mediated angiogenesis. J. Clin. Invest., 2005, 115(8), 2119-2127. doi: 10.1172/JCI24726 PMID: 16075056</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Zhang, Y.; Zhang, L.; Chu, W.; Wang, B.; Zhang, J.; Zhao, M.; Li, X.; Li, B.; Lu, Y.; Yang, B.; Shan, H. Tanshinone IIA inhibits miR-1 expression through p38 MAPK signal pathway in post-infarction rat cardiomyocytes. Cell. Physiol. Biochem., 2010, 26(6), 991-998. doi: 10.1159/000324012 PMID: 21220930</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Li, Y.S.; Wang, J.X.; Jia, M.M.; Liu, M.; Li, X.J.; Tang, H.B. Dragons blood inhibits chronic inflammatory and neuropathic pain responses by blocking the synthesis and release of substance P in rats. J. Pharmacol. Sci., 2012, 118(1), 43-54. doi: 10.1254/jphs.11160FP</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Choy, C.S.; Hu, C.M.; Chiu, W.T.; Lam, C.S.K.; Ting, Y.; Tsai, S.H.; Wang, T.C. Suppression of lipopolysaccharide-induced of inducible nitric oxide synthase and cyclooxygenase-2 by Sanguis Draconis, a dragons blood resin, in RAW 264.7 cells. J. Ethnopharmacol., 2008, 115(3), 455-462. doi: 10.1016/j.jep.2007.10.012 PMID: 18060707</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Ha, J.; Park, C.; Park, C.; Park, S. Improved prediction of miRNA-disease associations based on matrix completion with network regularization. Cells, 2020, 9(4), 881. doi: 10.3390/cells9040881 PMID: 32260218</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Ha, J.; Park, C. MLMD: Metric learning for predicting MiRNA-disease associations. IEEE Access, 2021, 9, 78847-78858. doi: 10.1109/ACCESS.2021.3084148</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Ha, J. SMAP: Similarity-based matrix factorization framework for inferring miRNA-disease association. Knowl. Base. Syst., 2023, 263, 110295. doi: 10.1016/j.knosys.2023.110295</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Ha, J. MDMF: Predicting miRNAdisease association based on matrix factorization with disease similarity constraint. J. Pers. Med., 2022, 12(6), 885. doi: 10.3390/jpm12060885 PMID: 35743670</mixed-citation></ref></ref-list></back></article>
