The Journal of Korean Medicine (대한한의학회지)

The Society of Korean Medicine (대한한의학회)
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Network pharmacology-based prediction of efficacy and mechanism of Chongmyunggongjin-dan acting on Alzheimer's disease

네트워크 약리학을 기반으로한 총명공진단(聰明供辰丹) 구성성분과 알츠하이머 타겟 유전자의 효능 및 작용기전 예측

  • Bitna Kweon (Department of Pharmacology, School of Korean Medicine, Wonkwang University) ;
  • Sumin Ryu (Department of Pharmacology, School of Korean Medicine, Wonkwang University) ;
  • Dong-Uk Kim (Department of Pharmacology, School of Korean Medicine, Wonkwang University) ;
  • Jin-Young Oh (Department of Pharmacology, School of Korean Medicine, Wonkwang University) ;
  • Mi-Kyung Jang (Department of Pharmacology, School of Korean Medicine, Wonkwang University) ;
  • Sung-Joo Park (Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University) ;
  • Gi-Sang Bae (Department of Pharmacology, School of Korean Medicine, Wonkwang University)
  • 권빛나 (원광대학교 한의과대학 약리학교실) ;
  • 유수민 (원광대학교 한의과대학 약리학교실) ;
  • 김동욱 (원광대학교 한의과대학 약리학교실) ;
  • 오진영 (원광대학교 한의과대학 약리학교실) ;
  • 장미경 (원광대학교 한의과대학 약리학교실) ;
  • 박성주 (원광대학교 한방심신증후군연구센터) ;
  • 배기상 (원광대학교 한의과대학 약리학교실)
  • Received : 2023.04.12
  • Accepted : 2023.05.10
  • Published : 2023.06.01
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Abstract

Objectives: Network pharmacology is a method of constructing and analyzing a drug-compound-target network to predict potential efficacy and mechanisms related to drug targets. In that large-scale analysis can be performed in a short time, it is considered a suitable tool to explore the function and role of herbal medicine. Thus, we investigated the potential functions and pathways of Chongmyunggongjin-dan (CMGJD) on Alzheimer's disease (AD) via network pharmacology analysis. Methods: Using public databases and PubChem database, compounds of CMGJD and their target genes were collected. The putative target genes of CMGJD and known target genes of AD were compared and found the correlation. Then, the network was constructed using Cytoscape 3.9.1. and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results: The result showed that total 104 compounds and 1157 related genes were gathered from CMGJD. The network consisted of 1157nodes and 10034 edges. 859 genes were interacted with AD gene set, suggesting that the effects of CMGJD are closely related to AD. Target genes of CMGJD are considerably associated with various pathways including 'Positive regulation of chemokine production', 'Cellular response to toxic substance', 'Arachidonic acid metabolic process', 'PI3K-Akt signaling pathway', 'Metabolic pathways', 'IL-17 signaling pathway' and 'Neuroactive ligand-receptor interaction'. Conclusion: Through a network pharmacological method, CMGJD was predicted to have high relevance with AD by regulating inflammation. This study could be used as a basis for effects of CMGJD on AD.

Keywords

Acknowledgement

이 논문은 정부(교육부)의 재원으로 한국연구재단의 지원을 받아 수행된 연구임(NRF-2021R1I1A2053285).

References

  1. Zhang, R.Zhu, X.Bai, H. & Ning, K. (2019). Network pharmacology databases for traditional chinese medicine: Review and assessment. Front Pharmacol. 10(123. 10.3389/fphar.2019.00123
  2. Talevi, A. (2015). Multi-target pharmacology: Possibilities and limitations of the "skeleton key approach" from a medicinal chemist perspective. Frontiers in pharmacology. 6(205).
  3. Shao, L. & Zhang, B. (2013). Traditional chinese medicine network pharmacology: Theory, methodology and application. Chinese journal of natural medicines. 11(2). 110-120. https://doi.org/10.1016/S1875-5364(13)60037-0
  4. Corson, T. W. & Crews, C. M. (2007). Molecular understanding and modern application of traditional medicines: Triumphs and trials. Cell. 130(5). 769-774. 10.1016/j.cell.2007.08.021
  5. Kim, M. H. (2023). Prediction of functional molecular machanism of astragalus membranaceus on obesity via network pharmacology analysis. The Korea Journal of Herbology. 38(1). 45-53. https://doi.org/10.6116/KJH.2023.38.1.45.
  6. Lee, W. Y.Lee, C. Y.Kim, Y. S. & Kim, C. E. (2019). The methodological trends of traditional herbal medicine employing network pharmacology. Biomolecules. 9(8). 10.3390/biom9080362
  7. Hopkins, A. L. (2008). Network pharmacology: The next paradigm in drug discovery. Nat Chem Biol. 4(11). 682-690. 10.1038/nchembio.118
  8. Lee, W. Y.Kim, C. E. & Lee, C. Y. (2021). A novel method to investigating korean medicine theory: Drug-centered approach employing network pharmacology. Journal of Physiology & Pathology in Korean Medicine. 35(5). 125-131. https://doi.org/10.15188/kjopp.2021.10.35.5.125
  9. Hwang, G.-s. & Shin, Y.-j. (2020). Protective effects of chongmyunggongjin-dan on h 2 o 2-induced c6 glial cell death. The Journal of Internal Korean Medicine. 41(1). 44-58. https://doi.org/10.22246/jikm.2020.41.1.44
  10. Lee, J.-H., Jo, D.-C., Kim, C.-G., Moon, S.-J., Park, T.-Y., Ko, Y.-S., et al. (2013). A literature review of effectiveness on the gongjin-dan (gongchen-dan). Journal of Korean Medicine Rehabilitation. 23(3). 69-78.
  11. Committee, O. M. T. E. (2015). Oriental herbal medicine (version 2). Shinilbooks.
  12. Park, E.-k.Shim, E.-s.Jung, H.-s.Sohn, N.-w. & Sohn, Y.-j. (2008). Effects of chongmyung-tang, polygalae radix and acori graminei rhizoma on aβ toxicity and memory dysfunction in mice. The journal of Internal Korean Medicine. 29(3). 608-620.
  13. Jang, H.-J., Sung, W.-Y., Lee, S.-H., Son, J.-H., Han, S.-H. & Jung, H.-C. (2004). A study of gongjin-dan in patients with mild dementia of alzheimer type. Journal of Oriental Neuropsychiatry. 15(2). 141-148.
  14. Baek, M. S., Kim, H. K., Han, K., Kwon, H. S., Na, H. K., Lyoo, C. H., et al. (2022). Annual trends in the incidence and prevalence of alzheimer's disease in south korea: A nationwide cohort study. Front Neurol. 13(883549. 10.3389/fneur.2022.883549
  15. Li, X., Feng, X., Sun, X., Hou, N., Han, F. & Liu, Y. (2022). Global, regional, and national burden of alzheimer's disease and other dementias, 1990-2019. Front Aging Neurosci. 14(937486. 10.3389/fnagi.2022.937486
  16. Silva, M. V. F., Loures, C. M. G., Alves, L. C. V., de Souza, L. C., Borges, K. B. G. & Carvalho, M. D. G. (2019). Alzheimer's disease: Risk factors and potentially protective measures. J Biomed Sci. 26(1). 33. 10.1186/s12929-019-0524-y
  17. Kang, H. & Park, K. W. (2015). Recent update of clinical drug trials in alzheimer's disease. Journal of the Korean Neurological Association. 33(4). 252-258. https://doi.org/10.17340/jkna.2015.4.2
  18. Hardy, J. & Selkoe, D. J. (2002). The amyloid hypothesis of alzheimer's disease: Progress and problems on the road to therapeutics. Science. 297(5580). 353-356. 10.1126/science.1072994
  19. Binder, L. I.Guillozet-Bongaarts, A. L.Garcia -Sierra, F. & Berry, R. W. (2005). Tau, tangles, and alzheimer's disease. Biochim Biophys Acta. 1739(2-3). 216-223. 10.1016/j.bbadis.2004.08.014
  20. Princiotta Cariddi, L.Mauri, M.Cosentino, M.Versino, M. & Marino, F. (2022). Alzheimer's disease: From immune homeostasis to neuroinflammatory condition. International Journal of Molecular Sciences. 23(21). 13008.
  21. Zuena, A. R.Casolini, P.Lattanzi, R. & Maftei, D. (2019). Chemokines in alzheimer's disease: New insights into prokineticins, chemokine-like proteins. Frontiers in pharmacology. 10(622.
  22. Nisa, F. Y., Rahman, M. A., Hossen, M. A., Khan, M. F., Khan, M. A. N., Majid, M., et al. (2021). Role of neurotoxicants in the pathogenesis of alzheimer's disease: A mechanistic insight. Ann Med. 53(1). 1476-1501. 10.1080/07853890.2021.1966088
  23. Thomas, M. H. & Olivier, J. L. (2016). Arachidonic acid in alzheimer's disease. Journal of Neurology & Neuromedicine. 1(9).
  24. Deng, X., Zhao, S., Liu, X., Han, L., Wang, R., Hao, H., et al. (2020). Polygala tenuifolia: A source for anti-alzheimer's disease drugs. Pharm Biol. 58(1). 410-416. 10.1080/13880209.2020.1758732
  25. Cheong, M. H., Lee, S. R., Yoo, H. S., Jeong, J. W., Kim, G. Y., Kim, W. J., et al. (2011). Anti-inflammatory effects of polygala tenuifolia root through inhibition of nf-kappab activation in lipopolysaccharide-induced bv2 microglial cells. J Ethnopharmacol. 137(3). 1402-1408. 10.1016/j.jep.2011.08.008
  26. Jiang, J., Kim, J. J., Kim, D. Y., Kim, M. K., Oh, N. H., Koppula, S., et al. (2012). Acorus gramineus inhibits microglia mediated neuroinflammation and prevents neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp)-induced mouse model of parkinson's disease. J Ethnopharmacol. 144(3). 506-513. 10.1016/j.jep.2012.09.026
  27. Jeong, J. W., Lee, H. H., Han, M. H., Kim, G. Y., Hong, S. H., Park, C., et al. (2014). Ethanol extract of poria cocos reduces the production of inflammatory mediators by suppressing the nf-kappab signaling pathway in lipopolysaccharide-stimulated raw 264.7 macrophages. BMC Complement Altern Med. 14(101. 10.1186/1472-6882-14-101
  28. Choi, J. G.Sim, Y.Kim, W.Kim, S. Y. & Oh, M. S. (2015). Effect of hoelen cum radix on learning and memory enhancement via stimulation of neuronal differentiation in the hippocampus of the mouse brain. The Korea Journal of Herbology. 30(2). 43-48.
  29. Xie, D., Deng, T., Zhai, Z., Qin, T., Song, C., Xu, Y., et al. (2023). Moschus exerted protective activity against h2o2-induced cell injury in pc12 cells through regulating nrf-2/are signaling pathways. Biomedicine & Pharmacotherapy. 159(114290.
  30. Park, Y.-H., Son, I. H., Kim, B., Lyu, Y.-S., Moon, H.-I. & Kang, H.-W. (2009). Poria cocos water extract (pcw) protects pc1 2 neuronal cells from beta-amyloid-induced cell death through antioxidant and antiapoptotic functions. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 64(11). 760-764.
  31. Wiatrak, B.Kubis-Kubiak, A.Piwowar, A. & Barg, E. (2020). Pc12 cell line: Cell types, coating of culture vessels, differentiation and other culture conditions. Cells. 9(4). 10.3390/cells9040958
  32. Almohaimeed, H. M., Batawi, A. H., Mohammedsaleh, Z. M., Al Jaouni, S., Mutlq Alsawat, S. A., Abd El Wahab, M. G., et al. (2021). Musk (moschus moschiferus) attenuates changes in main olfactory bulb of depressed mice: Behavioral, biochemical, and histopathological evidence. Front Behav Neurosci. 15(704180. 10.3389/fnbeh.2021.704180
  33. Youn, K. & Jun, M. (2012). Inhibitory effects of key compounds isolated from corni fructus on bace1 activity. Phytother Res. 26(11). 1714-1718. 10.1002/ptr.4638
  34. Sung, Y. H., Chang, H. K., Kim, S. E., Kim, Y. M., Seo, J. H., Shin, M. C., et al. (2009). Anti-inflammatory and analgesic effects of the aqueous extract of corni fructus in murine raw 264.7 macrophage cells. J Med Food. 12(4). 788-795. 10.1089/jmf.2008.1011
  35. Lee, S. H., Yang, H. W., Ding, Y., Wang, Y., Jeon, Y. J., Moon, S. H., et al. (2015). Anti-inflammatory effects of enzymatic hydrolysates of velvet antler in raw 264.7 cells in vitro and zebrafish model. EXCLI J. 14(1122-1132. 10.17179/excli2015-481
  36. Oh, Y. C.Jeong, Y. H.Li, W. & Go, Y. (2019). Angelicae gigantis radix regulates lps-induced neuroinflammation in bv2 microglia by inhibiting nf-kappab and mapk activity and inducing nrf-2 activity. Molecules. 24(20). 10.3390/molecules24203755