Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
권호 표지
DOI QR코드

DOI QR Code

Prediction of cerebral infarction suppression mechanism of the Sagunja-Tang through network pharmacology analysis

네트워크 약리학 분석을 통한 사군자탕(四君子湯)의 뇌경색 억제 기전 예측

  • Received : 2022.11.20
  • Accepted : 2022.11.22
  • Published : 2022.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : Sagunja-Tang is a famous prescription used in Korean medicine for the purpose of promoting vital energy, and there are few studies using Sagunja-Tang on cerebrovascular diseases yet. As previous studies confirmed that Sagunja-tang is highly likely to be used effectively for stroke, this study was intended to predict the mechanism through which Sagunja-tang would act effectively on stroke. Methods : In this study, a network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 30%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ 0.3 were applied. Using the above variables, the relations between target genes and diseases that are presumed to be involved in the selected bioavailable compounds were constructed in a network format, and proteins thought to play a major role were identified. Results : Among the compounds included in Sagunja-Tang, 26 bioavailable compounds were selected and it was confirmed that these compounds can be effectively used in cerebrovascular diseases such as Alzheimer's disease and stroke. These compounds are considered to act on proteins related in cell death and growth. The most important mechanism of action was predicted to be apoptosis, and the protein that is thought to play the most key action in this mechanism was caspase-3. Conclusions : In our future study, Sagunja-Tang will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.

Keywords

Acknowledgement

이 논문은 부산대학교 기본연구지원사업(2년)에 의하여 연구되었음.

References

  1. Poisson SN, Glidden D, Johnston SC, Fullerton HJ. Deaths from stroke in US young adults, 1989-2009. Neurology. 2014;83(23):2110-5. https://doi.org/10.1212/WNL.0000000000001042
  2. Bejot Y, Delpont B, Giroud M. Rising stroke incidence in young adults: More epidemiological evidence, more questions to be answered. J Am Heart Assoc. 2016;5(5):10.1161/JAHA.116.003661.
  3. Hadadha M, Vakili A, Bandegi AR. Effect of the inhibition of hydrogen sulfide synthesis on ischemic injury and oxidative stress biomarkers in a transient model of focal cerebral ischemia in rats. J Stroke Cerebrovasc Dis. 2015;24(12):2676-84. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.07.020
  4. Zhao P, Zhou R, Zhu XY, Hao YJ, Li N, Wang J, Niu Y, Sun T, Li YX, Yu JQ. Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice. Int J Mol Med. 2015;36(3):633-44. https://doi.org/10.3892/ijmm.2015.2260
  5. Durukan A, Tatlisumak T. Handbook of clinical neurology stroke, part 1 basic and epidemiological aspects: New York: Elsevier; 2009.
  6. Kim D. Animal models of stroke. Brain & NeuroRehabilitation. 2011;4(1):1-11. https://doi.org/10.12786/bn.2011.4.1.1
  7. Lee SE, Lim C, Lee M, Kim CH, Kim H, Lee B, Cho S. Assessing neuroprotective effects of Glycyrrhizae Radix et Rhizoma extract using a transient middle cerebral artery occlusion mouse model. J Vis Exp. 2018;142. doi(142):10.3791/58454.
  8. Lim C, Lim S, Lee B, Kim B, Cho S. Licorice pretreatment protects against brain damage induced by middle cerebral artery occlusion in mice. J Med Food. 2018;21(5):474-80.
  9. Lim C, Lim S, Lee B, Cho S. Selection for preclinical study candidate through analysis of frequently used medications presented in Donguibogam Stroke chapter. Herbal Formula Science. 2022;30(3):165-74. https://doi.org/10.14374/HFS.2022.30.3.165
  10. Lee SJ. Research trends on the effect of Sagunzatang and Samultang. Proceed Daejeon Univ Inst Kor Med. 2011;20(1):175-82.
  11. Lee KG, Huang DS, Yu YB, Ma JY, Ha HK, Shin HK. A study on compositions, dosages and usages of Sagunjatang, Samultang, Palmultang, Sipjeondaebotang in literature. J Korean Med Classics. 2006;19(4):219-25.
  12. Ru J, Li P, Wang J, Zhou W, Li B, Huang C, Li P, Guo Z, Tao W, Yang Y, Xu X, Li Y, Wang Y, Yang L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014;6:13.doi: 10.1186/1758-2946-6-13.
  13. KIOM. Defining Dictionary for Medicinal Herbs. Published on the Internet; https://oasis.kiom.re.kr/herblib/hminfo/hbmcod/hbmcodList.do (accessed 2022-11-02).
  14. STRING. https://string-db.org/ (accessed 2022-11-06).
  15. KEGG. Available from:URL;https://www.genome.jp/kegg/ (accessed 2022-11-06).
  16. Yang P, Tian Y, Deng W, Cai X, Liu W, Li L, Huang H. Sijunzi decoction may decrease apoptosis via stabilization of the extracellular matrix following cerebral ischaemia-reperfusion in rats. Exp Ther Med. 2019;18(4):2805-12.
  17. Liu L, Vollmer MK, Fernandez VM, Dweik Y, Kim H, Dore S. Korean red ginseng pretreatment protects against long-term sensorimotor deficits after ischemic stroke likely through Nrf2. Front Cell Neurosci. 2018;12:74.
  18. Ban JY, Kang SW, Lee JS, Chung JH, Ko YG, Choi HS. Korean red ginseng protects against neuronal damage induced by transient focal ischemia in rats. Exp Ther Med. 2012;3(4):693-8. https://doi.org/10.3892/etm.2012.449
  19. Zheng GQ, Cheng W, Wang Y, Wang XM, Zhao SZ, Zhou Y, Liu SJ, Wang XT. Ginseng total saponins enhance neurogenesis after focal cerebral ischemia. J Ethnopharmacol. 2011;133(2):724-8. https://doi.org/10.1016/j.jep.2010.01.064
  20. Tsutsumi YM, Tsutsumi R, Mawatari K, Nakaya Y, Kinoshita M, Tanaka K, Oshita S. Compound K, a metabolite of ginsenosides, induces cardiac protection mediated nitric oxide via Akt/PI3K pathway. Life Sci. 2011;88(15-16):725-9. https://doi.org/10.1016/j.lfs.2011.02.011
  21. Jin M, Kim K, Lim C, Cho S, Kim YK. Neuroprotective effects of Korean white ginseng and red ginseng in an ischemic stroke mouse model. J Ginseng Res. 2022;46(2):275-82. https://doi.org/10.1016/j.jgr.2021.06.012
  22. Yu XQ, Xue CC, Zhou ZW, Li CG, Du YM, Liang J, Zhou SF. In vitro and in vivo neuroprotective effect and mechanisms of glabridin, a major active isoflavan from Glycyrrhiza glabra (licorice). Life Sci. 2008;82(1-2):68-78. https://doi.org/10.1016/j.lfs.2007.10.019
  23. Kirsch DG, Doseff A, Chau BN, Lim DS, de Souza-Pinto NC, Hansford R, Kastan MB, Lazebnik YA, Hardwick JM. Caspase-3-dependent cleavage of Bcl-2 promotes release of cytochrome c. J Biol Chem. 1999;274(30):21155-61. https://doi.org/10.1074/jbc.274.30.21155
  24. Parrish AB, Freel CD, Kornbluth S. Cellular mechanisms controlling caspase activation and function. Cold Spring Harb Perspect Biol. 2013;5(6):10.1101/cshperspect.a008672.
  25. Sawe N, Steinberg G, Zhao H. Dual roles of the MAPK/ERK1/2 cell signaling pathway after stroke. J Neurosci Res. 2008;86(8):1659-69. https://doi.org/10.1002/jnr.21604
  26. Herceg Z, Wang ZQ. Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res. 2001;477(1-2):97-110. https://doi.org/10.1016/S0027-5107(01)00111-7
  27. Gao X, Zhang H, Takahashi T, Hsieh J, Liao J, Steinberg GK, Zhao H. The Akt signaling pathway contributes to postconditioning's protection against stroke; the protection is associated with the MAPK and PKC pathways. J Neurochem. 2008;105(3):943-55. https://doi.org/10.1111/j.1471-4159.2008.05218.x
  28. Fu R, Shen Y, Zheng J. Association between common genetic variants in ESR1 and stroke risk: A systematic review and meta-analysis. J Stroke Cerebrovasc Dis. 2019;28(11):104355.
  29. Wnuk A, Przepiorska K, Pietrzak BA, Kajta M. Post-treatment with amorfrutin B evokes PPARγ-mediated neuroprotection against hypoxia and ischemia. Biomedicines. 2021;9(8):854.doi: 10.3390/biomedicines9080854.