Research Articles

Multi-omics analysis reveals the neuroprotective effect of Atractylodis Rhizoma Alba extract against Parkinson’s disease in mouse

  • Sohi KANG ,
  • Sueun LEE ,
  • Byeong Cheol MOON ,
  • Jun Ho SONG ,
  • Sung-Ho KIM ,
  • Changjong MOON ,
  • Soong-In LEE ,
  • Chul KIM ,
  • Joong Sun KIM
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  • 1 Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea
    2 College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Republic of Korea
    3 Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111, Geonjae-ro, Naju-si, Jeollanam-do 58245, Republic of Korea
    4 Department of Biology, Chungbuk National University, Cheongju 28644, Republic of Korea
    5 Department of Oriental Medicine Prescription, College of Oriental Medicine, Dong-Shin University, Naju-si, Jeollanam-do 58245, Republic of Korea
    6 KM Data Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea

Received date: 2020-11-22

  Accepted date: 2023-12-06

  Online published: 2024-11-12

Supported by

Development of Sustainable Application for Standard Herbal Resource by the Korea Institute of Oriental Medicine(KSN2012320)

Abstract

OBJECTIVE: To assess Atractylodis Rhizoma Alba extract (ARE) neuroprotective function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and related genes.

METHODS: Examined mRNA-DNA methylation changes induced by ARE in MPTP-induced Parkinson’s disease (PD) model’s substantia nigra.

RESULTS: ARE mitigated MPTP-induced motor impairment in rotarod and open field tests and preserved tyrosine hydroxylase-positive neuronal cells in substantia nigra and striatum. Genome RNA-Sequencing and Methyl-Sequencing in substantia nigra of vehicle/ARE-treated MPTP-induced PD mice showed 84 differentially expressed genes (DEGs) and 1804 differentially methylated regions (DMRs). Upregulated genes involved zinc ion homeostasis, cilium protein localization, and transcription; downregulated genes linked to ephrin receptor signaling, somitogenesis, and gene expression regulation. Hyper/hypomethylated DMRs post-ARE treatment associated with Wnt signaling, mitochondrial organization, dopamine biosynthesis, and hindbrain development. No significant correlation between DEGs and methylated genes related to PD pathogenesis.

CONCLUSION: This research has identified the epigenetic targets of ARE's therapeutic action and gives insight on how ARE protects neurons in Parkinson's disease.

Cite this article

Sohi KANG , Sueun LEE , Byeong Cheol MOON , Jun Ho SONG , Sung-Ho KIM , Changjong MOON , Soong-In LEE , Chul KIM , Joong Sun KIM . Multi-omics analysis reveals the neuroprotective effect of Atractylodis Rhizoma Alba extract against Parkinson’s disease in mouse[J]. Journal of Traditional Chinese Medicine, 2024 , 44(6) : 1111 -1117 . DOI: 10.19852/j.cnki.jtcm.2024.06.002

References

1. Ministry of Food and Drug Safety. The Korean Pharmacopoeial Forum. 18th ed. North Chungcheong: Ministry of Food and Drug Safety, 2021: 116-23.
2. Zhang WJ, Zhao ZY, Chang LK, et al. Atractylodis Rhizoma: a review of its traditional uses, phytochemistry, pharmacology, toxicology and quality control. J Ethnopharmacol 2021; 266: 113415.
3. Zhu B, Zhang QL, Hua JW, Cheng WL, Qin LP. The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: a review. J Ethnopharmacol 2018; 226: 143-67.
4. Park ST, Lee MS, Jeon BH, Park KI, Oh JM. Effect of Atractylodis Rhizoma alba on osteoclast formation. J Physiol Pathol Kor Med 2011; 25: 109-14.
5. Choi S. Pharmacological and molecular studies of Atracylodes japonica Koidzumi on anti-oxidant activity. Seoul: KyungHee University, 2011: 1-29.
6. Han YK, Park YK. Effect of Atractylodis Rhizoma Alba water extract on streptozotocin-induced diabetes in rats. Korea J Herbol 2011; 26: 23-30.
7. Park CS, Kim DH. Biological activities of extracts from Scutellaria baicalensis, Zizyphus jujuba and Atractylodes macrocephala. Korea J Herbol 2008; 23: 41-51.
8. Lim SY, Kim HR, Choi YS, Lee I. Review of current clinical studies for herbal medicine of Parkinson’s disease in Traditional Chinese Medicine. J Physiol Pathol Kor Med 2016; 30: 327-37.
9. Jang JH, Jung K, Kim JS, Jung I, Yoo H, Moon C. Potential application of Yokukansan as a remedy for Parkinson’s disease. Evid Based Complement Alternat Med 2018; 2018.
10. Kim YE, Kim IW, Lee JH, Lee SG, Lee KS. Case report of Parkinson's disease diagnosed as deficiency of Qi and blood. J Intern Kor Med 2009; 30: 901-8.
11. Jeong HS, Kim HR, Kim SY, et al. Effects of Korean medicine on pain in patients with Parkinson's disease: a retrospective study. J Intern Kor Med 2020; 41: 947-58.
12. Kim SW, Yang JY, Lee YJ, et al. A case of Parkinson's disease patient with nausea and vomiting induced by taking levodopa. J Intern Kor Med 2019; 40: 246-53.
13. Lee SJ, Ha JB, Lew JH. A case study of parkinson's disease patient with anorexia and nausea treated with korean-medicine treatment including Hyangsayukgunja-tang. J Intern Kor Med 2020; 41: 717-23.
14. More S, Choi DK. Neuroprotective role of atractylenolide-I in an in vitro and in vivo model of Parkinson’s disease. Nutrients 2017; 9: 451.
15. Kang S, Lee SE, Lee A, et al. Protective effects of Atractylodis Rhizoma Alba Extract on seizures mice model. Korea J Herbol 2021; 36: 1-8.
16. Zuzuárregui JRP, During EH. Sleep issues in Parkinson’s disease and their management. Neurotherapeutics 2020; 17: 1480-94.
17. Lee E, Hwang I, Park S, et al. MPTP-driven NLRP3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration. Cell Death Differ 2019; 26: 213-28.
18. Latif S, Jahangeer M, Razia DM, et al. Dopamine in Parkinson's disease. Clin Chim Acta 2021; 522: 114-26.
19. Wada M, Ang MJ, Weerasinghe-Mudiyanselage PD, et al. Behavioral characterization in MPTP/p mouse model of Parkinson’s disease. J Integr Neurosci 2021; 20: 307-20.
20. Bossers K, Meerhoff G, Balesar R, et al. Analysis of gene expression in Parkinson's disease: possible involvement of neurotrophic support and axon guidance in dopaminergic cell death. Brain Pathol 2009; 19: 91-107.
21. Simunovic F, Yi M, Wang Y, et al. Gene expression profiling of substantia nigra dopamine neurons: further insights into Parkinson's disease pathology. Brain 2009; 132: 1795-809.
22. Duke D, Moran L, Kalaitzakis M, et al. Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson’s disease. Neurogenetics 2006; 7: 139-48.
23. Moran LB, Graeber MB. Towards a pathway definition of Parkinson’s disease: a complex disorder with links to cancer, diabetes and inflammation. Neurogenetics 2008; 9: 1-13.
24. Han HY, Yang YS, Kim SN, et al. Two-week repeated dose toxicity of Atractylodis Rhizoma Alba in F344 rats. Nat Prod Sci 2016; 22: 180-6.
25. Kim JS, Lim HS, Moon BC, et al. Epigenetic mechanisms involved in the neuroprotective effect of scorpion extract in a Parkinson's disease murine model based on multi-omics approach. J Tradit Chin Med 2021; 41: 390.
26. Meredith GE, Rademacher DJ. MPTP mouse models of Parkinson's disease: an update. J Parkinsons Dis 2011; 1: 19-33.
27. Rozas G, Guerra M, Labandeira-Garc?a J. An automated rotarod method for quantitative drug-free evaluation of overall motor deficits in rat models of parkinsonism. Brain Res Brain Res Protoc 1997; 2: 75-84.
28. Sedelis M, Schwarting RK, Huston JP. Behavioral phenotyping of the MPTP mouse model of Parkinson's disease. Behav Brain Res 2001; 125: 109-25.
29. Fernandez-Espejo E. Pathogenesis of Parkinson’s disease. Mol Neurobiol 2004; 29: 15-30.
30. Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron 2003; 39: 889-909.
31. Zhang T, Chen T, Chen P, Zhang B, Hong J, Chen L. MPTP-induced dopamine depletion in basolateral amygdala via decrease of D2R activation suppresses GABAA receptors expression and LTD induction leading to anxiety-like behaviors. Front Mol Neurosci 2017; 10: 247.
32. Jayaraj RL, Elangovan N, Manigandan K, Singh S, Shukla S. CNB-001 a novel curcumin derivative, guards dopamine neurons in MPTP model of Parkinson’s disease. BioMed research international 2014; 2014: 236182.
33. Bos JL, Rehmann H, Wittinghofer A. GEFs and GAPs: critical elements in the control of small G proteins. Cell 2007; 129: 865-77.
34. Xiong Y, Coombes CE, Kilaru A, et al. GTPase activity plays a key role in the pathobiology of LRRK2. PLoS Genet 2010; 6: e1000902.
35. Kang S, Kim JS, Lee J, Moon C, Kim C. Genome-wide analysis of DNA methylation and gene expression changes in MPTP-induced Parkinson’s diseases mouse model. Kor Herb Med Inform 2021; 9: 209-20.
36. Gogia N, Chimata AV, Deshpande P, Singh A, Singh A. Hippo signaling: bridging the gap between cancer and neurodegenerative disorders. Neural Regen Res 2021; 16: 643.
37. Caricasole A, Bakker A, Copani A, Nicoletti F, Gaviraghi G, Terstappen G. Two sides of the same coin: Wnt signaling in neurodegeneration and neuro-oncology. Biosci Rep 2005; 25: 309-27.
38. Inestrosa NC, Arenas E. Emerging roles of Wnts in the adult nervous system. Nat Rev Neurosci 2010; 11: 77-86.
39. Rawal N, Corti O, Sacchetti P, et al. Parkin protects dopaminergic neurons from excessive Wnt/β-catenin signaling. Biochem Biophys Res Commun 2009; 388: 473-8.
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