The Journal of Korean Medicine (대한한의학회지)

The Society of Korean Medicine (대한한의학회)
권호 표지
DOI QR코드

DOI QR Code

Screening of 56 Herbal formulas covered by the National Health Insurance Service on Dementia-related Factors

국민 건강보험 급여 한약 처방 56종의 치매 주요 생리지표 및 신경세포 변화에 대한 효능 비교 연구

  • Lim, Hye-Sun (Clinical Medicine Division, Korea Institute of Oriental Medicine) ;
  • Kim, Yu Jin (Clinical Medicine Division, Korea Institute of Oriental Medicine) ;
  • Kim, Yoon ju (Clinical Medicine Division, Korea Institute of Oriental Medicine) ;
  • Kim, Bu-Yeo (Clinical Medicine Division, Korea Institute of Oriental Medicine) ;
  • Jeong, Soo-Jin (Clinical Medicine Division, Korea Institute of Oriental Medicine)
  • 임혜선 (한국한의학연구원 임상의학부) ;
  • 김유진 (한국한의학연구원 임상의학부) ;
  • 김윤주 (한국한의학연구원 임상의학부) ;
  • 김부여 (한국한의학연구원 임상의학부) ;
  • 정수진 (한국한의학연구원 임상의학부)
  • Received : 2018.07.12
  • Accepted : 2018.09.07
  • Published : 2018.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: The purpose of this study was to investigate the effects of 56 herbal formulae covered by the National Health Insurance Corporation (NHIC) on dementia-related biomarkers and neuronal cell changes. Methods: The 56 herbal formulae were extracted with 70% ethanol at $100^{\circ}C$ for 2 h. The antioxidant properties was measured by radical scavenging assay using ABTS+ radical. The acetylcholinesterase (AChE) activity was tested by Ellman's assay and $amyloid-{\beta}$ ($A{\beta}$) aggregation was determined using fluorescence method. To estimate the inhibitory effects of herbal formulae on neuronal cell death and inflammation using HT22 hippocampal cells and BV-2 microglia, respectively. Results: Among the 56 herbal formulae, Dangguiyukhwangtang, Banhasasimtang, Samhwangsasimtang, Cheongwiesan, Hwangryunhaedoktang, Banhabaekchulchunmatang, Jaeumganghwatang, Cheongseoikgitang, and Hoechunyanggyuksan has a significant inhibitory effects on acetylcholinesterase (AChE) activity. Doinseunggitang and Samhwangsasimtang exerted the effect on the inhibition of $amyloid-{\beta}$ ($A{\beta}$) aggregation. Additionally, 10 herbal formulae affected AChE and $A{\beta}$ aggregation revealed antioxidant activity as well as neuroprotective and anti-neuroinflammation effects in neuronal cell lines. Conclusions: 10 herbal formulae that have been shown to be effective against the major dementia markers have been shown to have antioxidant activity, neuronal cell protection and inhibition of brain inflammation. Further investigation of these herbal formulae will need to be validated in dementia animal models.

Keywords

References

  1. Son CH, Kim YH, Lim S. A Study on Korean Oriental Medical Doctors' Use of Uninsured Herbal Extracts and How to Promote the Insurance Coverage of Such Herbal Extracts. J Korean Oriental Med. 2009;30(4):64-78.
  2. Burns A1, Iliffe S. Dementia. BMJ. 2009;338:b75. https://doi.org/10.1136/bmj.b75
  3. Akhondzadeh S, Abbasi SH. Herbal medicine in the treatment of Alzheimer's disease. Am J Alzheimers Dis Other Demen. 2006;21(2):113-8. https://doi.org/10.1177/153331750602100211
  4. Cho HY, Hong SS, Whang WW, Cho SH. A Retrospective Study on Dementia Outpatients in Oriental Neuropsychiatry Clinic of One Medical Center. J of Oriental Neuropsychiatry. 2010;21(4):137-49.
  5. Kim BG, Hyun KC, Kim JW, Whang WW. A Clinical Study on the Effects of Oriental Medical Treatment on Dementia of Alzheimer type. J of Oriental Neuropsychiatry. 1998;9(1);25-43.
  6. Terasawa K, Shimada Y, Kita T, Yamamoto T, Tosa H, Tanaka N, et al. Choto-san in the treatment of vascular dementia: a double-blind, placebo-controlled study. Phytomedicine. 1997;4(1):15-22. https://doi.org/10.1016/S0944-7113(97)80022-0
  7. Matsuda Y, Kishi T, Shibayama H, Iwata N. Yokukansan in the treatment of behavioral and psychological symptoms of dementia: a systematic review and meta-analysis of randomized controlled trials. Hum Psychopharmacol. 2013;28(1):80-6. https://doi.org/10.1002/hup.2286
  8. Lim HS, Kim Y, Kim OS, Jeong SJ. Screening of 50 Korean Herbal formulas with Inhibitory Effects on Acetylcholinesterase Activity and Amyloid-$\beta$ Aggregation. Kor J Pharmacogn. 2016;47(3):287-294.
  9. Ministry of Health and Welfare Notice. No. 2014-56. 2014 Apr 18.
  10. Lim HS, Ha H, Seo CS, Jin SE, Kim Y, Jeon WY, et al. Comparative study on efficacies and ingredient contents of different solvent extracts of Insampaedok-san. Kor. J. Herbology. 2012:27(6):115-122. https://doi.org/10.6116/kjh.2012.27.6.115
  11. Ellman GL, Courtney KD, Andres VJr, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88-95. https://doi.org/10.1016/0006-2952(61)90145-9
  12. Habtemariam S. The therapeutic potential of Berberis darwinii stem-bark: quantification of berberine and in vitro evidence for Alzheimer's disease therapy. Nat Prod Commun 2011:6(8): 1089-90.
  13. Hellstrand E, Boland B, Walsh DM, Linse S. Amyloid $\beta$-protein aggregation produces highly reproducible kinetic data and occurs by a two-phase process. ACS Chem. Neurosci. 2010;1:13-8. https://doi.org/10.1021/cn900015v
  14. Lemkul JA, Bevan DR. Morin inhibits the early stages of amyloid $\beta$-peptide aggregation by altering tertiary and quaternary interactions to produce "off-pathway" structures. Biochemistry. 2012:51(30):5990-6009. https://doi.org/10.1021/bi300113x
  15. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biol Med. 1999;26:1231-7. https://doi.org/10.1016/S0891-5849(98)00315-3
  16. Prince M, Ali GC, Guerchet M, Prina AM, Albanese E, Wu YT. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther. 2016;8(1):23. https://doi.org/10.1186/s13195-016-0188-8
  17. Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med. 2008;148(5):379-97. https://doi.org/10.7326/0003-4819-148-5-200803040-00009
  18. Naik RS, Hartmann J, Kiewert C, Duysen EG, Lockridge O, Klein J. Effects of rivastigmine and donepezil on brain acetylcholine levels in acetylcholinesterase-deficient mice. J Pharm Pharm Sci. 2009;12:79-85. https://doi.org/10.18433/J3MK59
  19. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA. 1993;90:7915-7922. https://doi.org/10.1073/pnas.90.17.7915
  20. Koo JS, Seo BI, Park JH, Roh SS. Analysis of papers on Oriental herbal medicines(prescriptions and herbs) for dementia. Kor J Herbology. 2010;25:131-137.
  21. Kim W, Jeon W, Heo E, Park S, Han C. Literature review and suggestions: dementia clinical studies in Korean Oriental Medicine. Kor J Orient Med. 2011;17:39-46.
  22. Vetrivel KS, Thinakaran G. Amyloidogenic processing of betaamyloid precursor protein in intracellular compartments. Neurology. 2006;66:S69-73. https://doi.org/10.1212/01.wnl.0000192393.05850.ec
  23. Eikelenboom P, van Gool WA. Neuroinflammatory perspectives on the two faces of Alzheimer's disease. J Neural Transm. 2004;111:281-94. https://doi.org/10.1007/s00702-003-0055-1
  24. Liu B, Hong JS. Role of microglia in inflammation-mediated neurodegenerative diseases:mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther. 2003;304:1-7. https://doi.org/10.1124/jpet.102.035048
  25. Ministry of Health and Welfare Notice. No. 2015-35. 2015 Feb 23.
  26. Hsu YL, Kuo PI, Tzeng TF, Sung SC, Yen MH, Lin YT, et al. Huang-lian-jie-du-tang, a traditional Chinese medicine prescription, induces cell-cycle arrest and apoptosis in human liver cancer cells in vitro and in vivo. J Gastroenterol Hepatol. 2008;23:e290-9. https://doi.org/10.1111/j.1440-1746.2008.05390.x
  27. Lu J, Wang JS, Kong LY. Anti-inflammatory effects of Huang-Lian-Jie-Du decoction, its two fractions and four typical compounds. J Ethnopharmacol. 2011;134:911-8. https://doi.org/10.1016/j.jep.2011.01.049
  28. Sasaki K, Sudo T, Kurusu T, Kiuchi T, Yoshizaki F. The mechanism of alteration of monoamine metabolism in brain regions in marble burying behavior-isolated housing mice and effect of oren-gedoku-to on this alteration. Yakugaku Zasshi. 2000;120(6):559-67. https://doi.org/10.1248/yakushi1947.120.6_559
  29. Chung SY, Kim JW, Lee JR, Jang HH, Kim HT, Whang WW. The Effects of Whangryonghaedoktang on Morris Water Maze and Tyrosine Hydroxylase Expression in Ventral Tegmental Area and Locus Coeruleus of the Chronic Mild Stress Animal Model of Depression. J of Oriental Neuropsychiatry. 2003;14(1):1-16.
  30. Guoxin DU, Shangqin LIU, Xiaoxi XIE, Li HE, Xiaoling ZHU, Wenyu RONG, et al. The efficacy of Huang-Lian-Jie-Du-Tang combined with chemotherapy for multiple myeloma. J Clinical Hematology. 2012;25(5):306-8.
  31. Sao L, Goto K, Shimada Y, Terasawa Y. Clinical comparative study of Huangyang detoxification hot water boiled rhubarb and atorvastatin for hyperlipidemia: including diet control, comparison with Placebo. Japan Toyo Kagaku Journal. 2004;55:236.
  32. Tohru S. Significance of Combined Use of Huangyaku Toxin for Insomnia in Manic Condition. Journal of Japan Toyo Medical Journal. 2004;55:179.
  33. Kim HY, Shin SH, Lee I. Neuroprotective Effect of Hwangryunhaedok-tang Against Glucosedeprivation Induced Cytotoxicity in PC-12 Cells. Korean J Oriental Physiology & Pathology. 2008;22(6):1462-9.
  34. Qing F, Xiaoping Z, Jianwei M, Mei S. The therapeutic effect of Huanglian Jiedu Decoction on AD rats and its effect on cytokine content. J of Tradit Chin Med. 2004;29(6):575-8.
  35. Qiu Y, Chen G, Mei G, Wang W, Wang K, Pan S. Effect of Huanglian Jiedu Decoction on free radical metabolism and IL-6, IL-$1{\beta}$ content in brain tissue of mice with APP/PS1 double transgenic Alzheimer's disease. Stroke and neurological diseases. 2011;18(2):72-4.
  36. Chen G, Shan P, Qiu Y. Clinical study of Huanglian Jiedu Decoction in the treatment of senile dementia (Heart and Liver). Chinese Journal of Emergency Medicine. 2007;16(4):386-7.
  37. Ministry of Health and Welfare Notice. No. 2017-214. 2017 Nov 27.
  38. Lee JY, Kook YB. Effects of Samhwangsasimtang on obesity-related metabolic disease in mice. Herbal formula science. 2014;22(1):93-104. https://doi.org/10.14374/HFS.2014.22.1.093
  39. Lee HC, Jeong MY, Choi JH, Park SY. Effects of Samhwangsasim-tang Gamibang on Atopic Dermatitis in Mice. Herbal formula science. 2017;25(3)337-47. https://doi.org/10.14374/HFS.2017.25.3.337
  40. Koo JS, Kwon DK, Seo BI, Park JH, Roh SS, Kim SM, et al. The Antimicrobial Activity of Samhwangsasimtang against pseudomonas aeruginosa 38 isolated from an acne patient. Kor J Herbology. 2010;25(2):11-9. https://doi.org/10.6116/KJH.2010.25.2.011
  41. Seok SH, Kim JH, Kim GW, Koo BS. A case of insomnia incurable by neuropsychiatric medication alone, but made possible with Sam-Hwang-Sa-Sim-Tang. J of Oriental Neuropsychiatry. 2006; 17(3):117-29.
  42. Shin SU, Lee JS, Kim SS. Effect of modified Samhwangsasim-tang(三黃瀉心湯加味方) on Suspicious Dementia of Multiple Infarction Induced by Hypoxia: A Case ReportJ Oriental Rehab Med. 2001;11(2):219-26