Biomolecules & Therapeutics

  • 제31권4호
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  • Pages.417-424
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  • 2023
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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6-Shogaol, an Active Ingredient of Ginger, Improves Intestinal and Brain Abnormalities in Proteus Mirabilis-Induced Parkinson's Disease Mouse Model

  • Eugene Huh (Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University) ;
  • Jin Gyu Choi (Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University) ;
  • Yujin Choi (Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • In Gyoung Ju (Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University) ;
  • Dongjin Noh (Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University) ;
  • Dong-yun Shin (College of Pharmacy, Gachon University) ;
  • Dong Hyun Kim (Neurobiota Research Center, College of Pharmacy, Kyung Hee University) ;
  • Hi-Joon Park (Acupuncture and Meridian Science Research Center (AMSRC), College of Korean Medicine, Kyung Hee University) ;
  • Myung Sook Oh (Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University)
  • 투고 : 2023.05.19
  • 심사 : 2023.05.30
  • 발행 : 2023.07.01
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초록

Parkinson's disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus mirabilis (P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

키워드

과제정보

This study was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education [NRF-2018R1D1A1B07048099] and grants from the National Research Foundation of Korea funded by the Korean government [2022M3A9B6017813].

참고문헌

  1. Angelopoulou, E., Paudel, Y. N., Papageorgiou, S. G. and Piperi, C. (2022) Elucidating the beneficial effects of ginger (Zingiber officinale Roscoe) in Parkinson's disease. ACS Pharmacol. Transl. Sci. 5, 838-848. https://doi.org/10.1021/acsptsci.2c00104
  2. Choi, J. G., Kim, N., Ju, I. G., Eo, H., Lim, S. M., Jang, S. E., Kim, D. H. and Oh, M. S. (2018) Oral administration of Proteus mirabilis damages dopaminergic neurons and motor functions in mice. Sci. Rep. 8, 1275.
  3. Choi, J. S., Bae, W. Y., Park, C. and Jeong, J. W. (2015) Zingerone activates VMAT2 during MPP(+) -induced Cell Death. Phytother. Res. 29, 1783-1790. https://doi.org/10.1002/ptr.5435
  4. Deol, P. K., Khare, P., Singh, D. P., Soman, G., Bishnoi, M., Kondepudi, K. K. and Kaur, I. P. (2017) Managing colonic inflammation associated gut derangements by systematically optimised and targeted ginger extract-Lactobacillus acidophilus loaded pharmacobiotic alginate beads. Int. J. Biol. Macromol. 105, 81-91. https://doi.org/10.1016/j.ijbiomac.2017.06.117
  5. Forsythe, P. and Bienenstock, J. (2010) Immunomodulation by commensal and probiotic bacteria. Immunol. Invest. 39, 429-448. https://doi.org/10.3109/08820131003667978
  6. Huh, E., Choi, J. G., Noh, D., Yoo, H. S., Ryu, J., Kim, N. J., Kim, H. and Oh, M. S. (2020) Ginger and 6-shogaol protect intestinal tight junction and enteric dopaminergic neurons against 1-methyl4-phenyl 1,2,3,6-tetrahydropyridine in mice. Nutr. Neurosci. 23, 455-464. https://doi.org/10.1080/1028415X.2018.1520477
  7. Huh, E., Lim, S., Kim, H. G., Ha, S. K., Park, H. Y., Huh, Y. and Oh, M. S. (2018) Ginger fermented with Schizosaccharomyces pombe alleviates memory impairment via protecting hippocampal neuronal cells in amyloid beta(1-42) plaque injected mice. Food Funct. 9, 171-178. https://doi.org/10.1039/C7FO01149K
  8. Kabuto, H., Nishizawa, M., Tada, M., Higashio, C., Shishibori, T. and Kohno, M. (2005) Zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone] prevents 6-hydroxydopamine-induced dopamine depression in mouse striatum and increases superoxide scavenging activity in serum. Neurochem. Res. 30, 325-332. https://doi.org/10.1007/s11064-005-2606-3
  9. Kabuto, H. and Yamanushi, T. T. (2011) Effects of zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone] and eugenol [2-methoxy-4-(2-propenyl)phenol] on the pathological progress in the 6-hydroxydopamine-induced Parkinson's disease mouse model. Neurochem. Res. 36, 2244-2249. https://doi.org/10.1007/s11064-011-0548-5
  10. Kelly, L. P., Carvey, P. M., Keshavarzian, A., Shannon, K. M., Shaikh, M., Bakay, R. A. and Kordower, J. H. (2014) Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson's disease. Mov. Disord. 29, 999-1009. https://doi.org/10.1002/mds.25736
  11. Kumar, N. V., Murthy, P. S., Manjunatha, J. R. and Bettadaiah, B. K. (2014) Synthesis and quorum sensing inhibitory activity of key phenolic compounds of ginger and their derivatives. Food Chem. 159, 451-457. https://doi.org/10.1016/j.foodchem.2014.03.039
  12. Li, Y., Xu, B., Xu, M., Chen, D., Xiong, Y., Lian, M., Sun, Y., Tang, Z., Wang, L., Jiang, C. and Lin, Y. (2017) 6-Gingerol protects intestinal barrier from ischemia/reperfusion-induced damage via inhibition of p38 MAPK to NF-kappaB signalling. Pharmacol. Res. 119, 137-148. https://doi.org/10.1016/j.phrs.2017.01.026
  13. Luettig, J., Rosenthal, R., Lee, I. M., Krug, S. M. and Schulzke, J. D. (2016) The ginger component 6-shogaol prevents TNF-alphainduced barrier loss via inhibition of PI3K/Akt and NF-kappaB signaling. Mol. Nutr. Food Res. 60, 2576-2586. https://doi.org/10.1002/mnfr.201600274
  14. Manju, V. and Nalini, N. (2006) Effect of ginger on bacterial enzymes in 1,2-dimethylhydrazine induced experimental colon carcinogenesis. Eur. J. Cancer Prev. 15, 377-383. https://doi.org/10.1097/00008469-200610000-00001
  15. Moon, M., Kim, H. G., Choi, J. G., Oh, H., Lee, P. K., Ha, S. K., Kim, S. Y., Park, Y., Huh, Y. and Oh, M. S. (2014) 6-Shogaol, an active constituent of ginger, attenuates neuroinflammation and cognitive deficits in animal models of dementia. Biochem. Biophys. Res. Commun. 449, 8-13. https://doi.org/10.1016/j.bbrc.2014.04.121
  16. Na, J. Y., Song, K., Lee, J. W., Kim, S. and Kwon, J. (2016) 6-Shogaol has anti-amyloidogenic activity and ameliorates Alzheimer's disease via CysLT1R-mediated inhibition of cathepsin B. Biochem. Biophys. Res. Commun. 477, 96-102. https://doi.org/10.1016/j.bbrc.2016.06.026
  17. Park, G., Kim, H. G., Ju, M. S., Ha, S. K., Park, Y., Kim, S. Y. and Oh, M. S. (2013) 6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation. Acta Pharmacol. Sin. 34, 1131-1139. https://doi.org/10.1038/aps.2013.57
  18. Peng, S., Yao, J., Liu, Y., Duan, D., Zhang, X. and Fang, J. (2015) Activation of Nrf2 target enzymes conferring protection against oxidative stress in PC12 cells by ginger principal constituent 6-shogaol. Food Funct. 6, 2813-2823. https://doi.org/10.1039/C5FO00214A
  19. Raza, C., Anjum, R. and Shakeel, N. U. A. (2019) Parkinson's disease: Mechanisms, translational models and management strategies. Life Sci. 226, 77-90. https://doi.org/10.1016/j.lfs.2019.03.057
  20. Samanta, A. K., Jayaram, C., Jayapal, N., Sondhi, N., Kolte, A. P., Senani, S., Sridhar, M. and Dhali, A. (2015) Assessment of fecal microflora changes in pigs supplemented with herbal residue and prebiotic. PLoS One 10, e0132961.
  21. Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., Chesselet, M. F., Keshavarzian, A., Shannon, K. M., KrajmalnikBrown, R., Wittung-Stafshede, P., Knight, R. and Mazmanian, S. K. (2016) Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell 167, 1469-1480.e12. https://doi.org/10.1016/j.cell.2016.11.018
  22. Scheperjans, F., Aho, V., Pereira, P. A., Koskinen, K., Paulin, L., Pekkonen, E., Haapaniemi, E., Kaakkola, S., Eerola-Rautio, J., Pohja, M., Kinnunen, E., Murros, K. and Auvinen, P. (2015) Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov. Disord. 30, 350-358. https://doi.org/10.1002/mds.26069