The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology (한방안이비인후피부과학회지)

The Society of Korean Medicine Ophthalmology, Otolaryngology & Dermatology (대한한방안이비인후피부과학회)
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Analysis of the Active Compounds and Therapeutic Mechanisms of Yijin-tang on Meniere's Disease Using Network Pharmacology(I)

네트워크 약리학을 활용한 메니에르병에 대한 이진탕(二陳湯)의 활성 성분과 치료 기전 연구(I)

  • SunKyung, Jin (Department of Ophthalmology, Otolaryngology and Dermatology of Korean Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Hae-Jeong, Nam (Department of Ophthalmology, Otolaryngology and Dermatology of Korean Medicine, College of Korean Medicine, Kyung Hee University)
  • 진선경 (경희대학교 한의과대학 안이비인후피부과학교실) ;
  • 남혜정 (경희대학교 한의과대학 안이비인후피부과학교실)
  • Received : 2023.01.07
  • Accepted : 2023.02.07
  • Published : 2023.02.25
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Abstract

Objectives : This study used a network pharmacology approach to explore the active compounds and therapeutic mechanisms of Yijin-tang on Meniere's disease. Methods : The active compounds of Yijin-tang were screened via the TCMSP database and their target proteins were screened via the STITCH database. The GeneCard was used to establish the Meniere's disease-related genes. The intersection targets were obtained through Venny 2.1.0. The related protein interaction network was constructed with the STRING database, and topology analysis was performed through CytoNCA. GO biological function analysis and KEGG enrichment analysis for core targets were performed through the ClueGO. Results : Network analysis identified 126 compounds in five herbal medicines of Yijin-tang. Among them, 15 compounds(naringenin, beta-sitosterol, stigmasterol, baicalein, baicalin, calycosin, dihydrocapsaicin, formononetin, glabridin, isorhamnetin, kaempferol, mairin, quercetin, sitosterol, nobiletin) were the key chemicals. The target proteins were 119, and 7 proteins(TNF, CASP9, PARP1, CCL2, CFTR, NOS2, NOS1) were linked to Meniere's disease-related genes. Core genes in this network were TNF, CASP9, and NOS2. GO/KEGG pathway analysis results indicate that these targets are primarily involved in regulating biological processes, such as excitotoxicity, oxidative stress, and apoptosis. Conclusion : Pharmacological network analysis can help to explain the applicability of Yijin-tang on Meniere's disease.

Keywords

References

  1. Espinosa-Sanchez JM, Lopez-Escamez JA. Meniere's disease. Handbook of clinical neurology. 2016;137:257-77. https://doi.org/10.1016/B978-0-444-63437-5.00019-4
  2. Yokota Y, Kitahara T, Sakagami M, Ito T, Kimura T, Okayasu T, et al. Surgical results and psychological status in patients with intractable Meniere's disease. Auris Nasus Larynx. 2016;43(3):287-91. https://doi.org/10.1016/j.anl.2015.10.007
  3. Baloh RW. Harold Schuknecht and pathology of the ear. Otology & neurotology. 2001; 22(1):113-22. https://doi.org/10.1097/00129492-200101000-00021
  4. Kiang NYS. An auditory physiologist's view of Meniere's syndrome. 2nd Int Symp Men Dis. Amsterdam:Kugler. 1989:13-24.
  5. Jung SC, Kim YJ. The bibliographicol study on Yijin-tang(sang). Journal of Haehwa Medicine. 2002;11(1):29-41.
  6. Park WH, Choi DY. The bibliographicol study on Dam-Eum. The Journal of Dong Guk Oriental Medicine. 1992;1(1):141-60.
  7. Jung HJ, Ko WS, Yoon HJ. Korean Medicinal Review of the Latest Research Trend on Pathology of Meniere's Disease. J Korean Med Ophtahlmol Otolaryngol Dermatol. 2017;30(3):103-18.
  8. Li S, Fan TP, Jia W, Lu A, Zhang W. Network pharmacology in traditional Chinese medicine. Evidence-based complementary and alternative medicine. 2014;2014:2.
  9. Lee WY, Lee CY, Kim YS, Kim CE. The methodological trends of traditional herbal medicine employing network pharmacology. Biomolecules. 2019;9(8):362.
  10. Lee AY, Park W, Kang TW, Cha MH, Chun JM. Network pharmacology-based prediction of active compounds and molecular targets in Yijin-Tang acting on hyperlipidaemia and atherosclerosis. Journal of Ethnopharmacology. 2018;221:151-9. https://doi.org/10.1016/j.jep.2018.04.027
  11. Liu H, Xu J, Li H, Zhang L, Xu P. Network pharmacology-based investigation to explore the effect and mechanism of Erchen decoction against the nonalcoholic fatty liver disease. The Anatomical Record. 2021; 304(11):2605-19. https://doi.org/10.1002/ar.24770
  12. Ding S, Chen Q, Huang Y, Li X, Chai Y, Li C, et al. Exploring miRNA-related molecular targets of erchen decoction against lipid metabolism disorder using A network pharmacologic approach. Combinatorial Chemistry & High Throughput Screening. 2022;25(6):986-97. https://doi.org/10.2174/1386207324666210302093300
  13. Bradley J. TNF-mediated inflammatory disease. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland. 2008;214(2):149-60. https://doi.org/10.1002/path.2287
  14. Frejo L, Gallego-Martinez A, Requena T, Martin-Sanz E, Amor-Dorado JC, Soto-Varela A, et al. Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease. Scientific reports. 2018;8(1):1-11. https://doi.org/10.1038/s41598-018-23911-4
  15. Patel JA, Nair S, Revai K, Grady J, Saeed K, Matalon R, et al. Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media. Pediatrics. 2006;118(6):2273-9. https://doi.org/10.1542/peds.2006-0764
  16. Keithley EM, Wang X, Barkdull GC. Tumor necrosis factor α can induce recruitment of inflammatory cells to the cochlea. Otology & Neurotology. 2008;29(6):854-9. https://doi.org/10.1097/MAO.0b013e31818256a9
  17. Huang CJ, Wan TK, Fang TY, Wang PC. CASP9 genotype confers gentamicin susceptibility in intratympanic treatment of intractable vertigo caused by Meniere's disease. Acta Oto-Laryngologica. 2019;139 (4):336-9. https://doi.org/10.1080/00016489.2019.1575525
  18. Junet P, Karkas A, Dumas G, Quesada JL, Schmerber S. Vestibular results after intratympanic gentamicin therapy in disabling Meniere's disease. European Archives of Oto-Rhino-Laryngology. 2016;273(10):3011-8. https://doi.org/10.1007/s00405-015-3889-x
  19. Cunningham LL, Cheng AG, Rubel EW. Caspase activation in hair cells of the mouse utricle exposed to neomycin. Journal of Neuroscience. 2002;22(19):8532-40. https://doi.org/10.1523/jneurosci.22-19-08532.2002
  20. MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Annual review of immunology. 1997;15:323.
  21. Hess A, Bloch W, Huverstuhl J, Su J, Stennert E, Addicks K, et al. Expression of inducible nitric oxide synthase(iNOS/NOS II) in the cochlea of guinea pigs after intratympanical endotoxin-treatment. Brain research. 1999;830(1):113-22. https://doi.org/10.1016/S0006-8993(99)01433-X
  22. Lechner M, Lirk P, Rieder J. Inducible nitric oxide synthase(iNOS) in tumor biology: the two sides of the same coin. Seminars in cancer biology. 2005;15(4):277-89. https://doi.org/10.1016/j.semcancer.2005.04.004
  23. Michel O, Hess A, Su J, Bloch W, Stennert E, Addicks K. Expression of inducible nitric oxide synthase(iNOS/NOS II) in the hydropic cochlea of guinea pigs. Hearing research. 2000;143(1,2):23-8. https://doi.org/10.1016/S0378-5955(00)00018-6
  24. Msiv NP, Zdanski CJ, Gregory CW, Prazma J, Carrasco V. Sodium nitroprusside/nitric oxide causes apoptosis in spiral ganglion cells. Otolaryngology-Head and Neck Surgery. 1998;119(4):323-30. https://doi.org/10.1016/S0194-5998(98)70072-5
  25. Ishiyama G, Lopez IA, Ishiyama P, Vinters HV, Ishiyama A. The blood labyrinthine barrier in the human normal and Meniere's disease macula utricle. Scientific reports. 2017;7(1):1-10. https://doi.org/10.1038/s41598-016-0028-x
  26. Ishiyama G, Wester J, Lopez IA, Beltran-Parrazal L, Ishiyama A. Oxidative stress in the blood labyrinthine barrier in the macula utricle of Meniere's disease patients. Frontiers in Physiology. 2018;9:1068.
  27. Suslu N, Yilmaz T, Gursel B. Utility of immunologic parameters in the evaluation of Meniere's disease. Acta oto-laryngologica. 2009;129(11):1160-5. https://doi.org/10.3109/00016480802631966
  28. Gazquez I, Lopez-Escamez JA, Moreno A, Campbell CA, Meyer NC, Carey J, et al. Functional variants in NOS1 and NOS2A are not associated with progressive hearing loss in Meniere's disease in a European Caucasian population. DNA and cell biology. 2011;30(9):699-708. https://doi.org/10.1089/dna.2011.1259
  29. Merchant SN, Adams JC, Nadol Jr JB. Pathophysiology of Meniere's syndrome: are symptoms caused by endolymphatic hydrops?. Otology & Neurotology. 2005;26(1):74-81. https://doi.org/10.1097/00129492-200501000-00013
  30. Semaan MT, Alagramam KN, Megerian CA. The basic science of Meniere's disease and endolymphatic hydrops. Current opinion in otolaryngology & head and neck surgery. 2005;13(5):301-7. https://doi.org/10.1097/01.moo.0000186335.44206.1c
  31. Frejo L, Lopez-Escamez JA. Cytokines and inflammation in Meniere disease. Clinical and Experimental Otorhinolaryngology. 2022;15(1):49.
  32. Pazzaglia S, Pioli C. Multifaceted role of PARP-1 in DNA repair and inflammation: pathological and therapeutic implications in cancer and non-cancer diseases. Cells. 2019;9(1):41.
  33. Morgenstern C, Mori N, Amano H. Pathogenesis of experimental endolymphatic hydrops. Acta Oto-Laryngologica. 1983;96(406):56-8. https://doi.org/10.3109/00016488309123003
  34. Pawankar R, Tomiyama S, Ikezono T, Nonaka M, Jinnouchi K, Yagi T. Interferon-gamma expression in the inner ear of rats following secondary immune reaction in the endolymphatic sac. Acta Otolaryngol Suppl. 2004;553:6-12. https://doi.org/10.1080/03655230410017580
  35. Satoh H, Firestein GS, Billings PB, Harris JP, Keithley EM. Proinflammatory cytokine expression in the endolymphatic sac during inner ear inflammation. Journal of the Association for Research in Otolaryngology. 2003;4(2):139-47. https://doi.org/10.1007/s10162-002-3025-7
  36. Matsubara A, Miyashita T, Inamoto R, Hoshikawa H, Mori N. Cystic fibrosis transmembrane conductance regulator in the endolymphatic sac of the rat. Auris Nasus Larynx. 2014;41(5):409-12.  https://doi.org/10.1016/j.anl.2014.02.005