Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Author(s): Xin Su, Hongwei Xue, Yang Lou, Xinkai Lv, Xiao Mi, Juan Lu* and Xi Chen*

DOI: 10.2174/0113862073264485240102064653

DownloadDownload PDF Flyer Cite As
Investigation of the Potential Mechanism of Compound Dragon's Blood Capsule against Myocardial Ischemia Based on Network Pharmacology

Page: [2940 - 2950] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

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.

Aim: The present study aims to reveal the potential mechanisms of CDC’s anti-myocardial ischemia effect.

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.

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.

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.

[1]
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.
[http://dx.doi.org/10.1038/s41569-018-0119-4] [PMID: 30467329]
[2]
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.
[http://dx.doi.org/10.1097/PSY.0b013e3182a893ae] [PMID: 24163385]
[3]
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.
[http://dx.doi.org/10.3892/etm.2012.766] [PMID: 23251290]
[4]
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.
[http://dx.doi.org/10.1155/2016/7580731] [PMID: 27087891]
[5]
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.
[6]
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.
[http://dx.doi.org/10.1016/j.biopha.2017.07.063] [PMID: 28738535]
[7]
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.
[http://dx.doi.org/10.1016/j.biopha.2018.03.142] [PMID: 29710540]
[8]
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.
[http://dx.doi.org/10.1007/s12035-019-01668-9] [PMID: 31203572]
[9]
Dvir, D.; Battler, A. Conventional and novel drug therapeutics to relief myocardial ischemia. Cardiovasc. Drugs Ther., 2010, 24(4), 319-323.
[http://dx.doi.org/10.1007/s10557-010-6254-8] [PMID: 20658184]
[10]
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.
[http://dx.doi.org/10.1371/journal.pone.0088137] [PMID: 24505402]
[11]
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.
[12]
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.
[http://dx.doi.org/10.1002/ptr.5787] [PMID: 28164397]
[13]
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.
[http://dx.doi.org/10.1002/ptr.2565] [PMID: 18814204]
[14]
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.
[http://dx.doi.org/10.1016/j.jep.2023.116306] [PMID: 36858276]
[15]
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.
[http://dx.doi.org/10.2147/DDDT.S207955] [PMID: 31564827]
[16]
Liu, A.L.; Du, G.H. Network pharmacology: New guidelines for drug discovery. Acta Pharmacol. Sin., 2010, 45(12), 1472-1477.
[17]
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.
[http://dx.doi.org/10.21203/rs.3.rs-1086482/v1]
[18]
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.
[http://dx.doi.org/10.1016/j.ejphar.2023.176044] [PMID: 37660968]
[19]
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.
[http://dx.doi.org/10.1142/S0192415X21500907] [PMID: 34775933]
[20]
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.
[http://dx.doi.org/10.1016/j.jgr.2018.12.001] [PMID: 32913396]
[21]
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.
[http://dx.doi.org/10.7150/ijms.64984] [PMID: 34975299]
[22]
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.
[http://dx.doi.org/10.1590/1414-431x20199106] [PMID: 31994603]
[23]
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.
[24]
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.
[http://dx.doi.org/10.3390/cells9010243] [PMID: 31963688]
[25]
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.
[http://dx.doi.org/10.18632/aging.203578] [PMID: 34607973]
[26]
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.
[27]
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.
[http://dx.doi.org/10.1016/j.cyto.2015.11.006] [PMID: 26551859]
[28]
Tedgui, A.; Mallat, Z. [Inflammation and atherosclerosis]. Nephrologie, 2003, 24(7), 411-414.
[PMID: 14650755]
[29]
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.
[http://dx.doi.org/10.1177/1074248412438102] [PMID: 22396328]
[30]
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.
[http://dx.doi.org/10.1142/S0192415X13500845] [PMID: 24228599]
[31]
Blaustein, M.P.; Lederer, W.J. Sodium/calcium exchange: Its physiological implications. Physiol. Rev., 1999, 79(3), 763-854.
[http://dx.doi.org/10.1152/physrev.1999.79.3.763] [PMID: 10390518]
[32]
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.
[http://dx.doi.org/10.1016/j.pbiomolbio.2005.05.011] [PMID: 16009403]
[33]
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.
[http://dx.doi.org/10.1016/j.cmet.2007.10.007] [PMID: 18054314]
[34]
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.
[http://dx.doi.org/10.1172/JCI24726] [PMID: 16075056]
[35]
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.
[http://dx.doi.org/10.1159/000324012] [PMID: 21220930]
[36]
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.
[http://dx.doi.org/10.1254/jphs.11160FP]
[37]
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.
[http://dx.doi.org/10.1016/j.jep.2007.10.012] [PMID: 18060707]
[38]
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.
[http://dx.doi.org/10.3390/cells9040881] [PMID: 32260218]
[39]
Ha, J.; Park, C. MLMD: Metric learning for predicting MiRNA-disease associations. IEEE Access, 2021, 9, 78847-78858.
[http://dx.doi.org/10.1109/ACCESS.2021.3084148]
[40]
Ha, J. SMAP: Similarity-based matrix factorization framework for inferring miRNA-disease association. Knowl. Base. Syst., 2023, 263, 110295.
[http://dx.doi.org/10.1016/j.knosys.2023.110295]
[41]
Ha, J. MDMF: Predicting miRNA–disease association based on matrix factorization with disease similarity constraint. J. Pers. Med., 2022, 12(6), 885.
[http://dx.doi.org/10.3390/jpm12060885] [PMID: 35743670]