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Mulberry fruit ameliorates Parkinson's-disease-related pathology by reducing α-synuclein and ubiquitin levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model.
J Nutr Biochem. 2017 01; 39:15-21.JN

Abstract

Mulberry fruit, which has been long used in traditional oriental medicine, was reported to ameliorate motor dysfunction and dopaminergic neuronal degeneration via antioxidant and antiapoptotic effects in an animal model of Parkinson's disease (PD). More than 95% of PD patients exhibit nonmotor problems such as olfactory dysfunction and gastrointestinal constipation, which are generally considered to be early symptoms of PD. However, few studies have actually examined potential drugs to treat early PD symptoms. The present study examined the protective effects of mulberry fruit extract (ME) against neurotoxicity in a 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) model of early PD. MPTP/p model was developed by systemic administration with MPTP (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. The behavioral studies showed that treatment of mice with ME significantly improved PD-related nonmotor symptoms as well as motor impairment, demonstrated by utilizing the olfactory, pole, rotarod and open field tests. In addition, immunohistochemical analysis indicated that ME exhibits the protective effects against dopaminergic neuronal damage induced by MPTP/p in the substantia nigra and striatum. Moreover, by using Western blot analysis, we found that treatment with ME inhibited the up-regulation of α-synuclein and ubiquitin, well known as composition of Lewy bodies in the substantia nigra and striatum of the MPTP/p mice. Taken together, these data suggest that ME may have therapeutic potential for preventing PD.

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Authors+Show Affiliations

Gu PS
Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
Moon M
Department of Biochemistry, College of Medicine, Konyang University, 158 Gwanjeodong-ro, Seo-gu, Daejeon, 302-718, Republic of Korea.
Choi JG
Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
Oh MS
Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 130-701, Republic of Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 130-701, Republic of Korea. Electronic address: msohok@khu.ac.kr.

MeSH

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsAntioxidantsCorpus StriatumDisease Models, AnimalDopaminergic NeuronsFruitGene Expression RegulationMaleMiceMice, Inbred C57BLMorusNeuroprotective AgentsParkinson DiseasePlant ExtractsProbenecidSubstantia NigraUbiquitinalpha-Synuclein

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27741433

Citation

Gu, Pil Sung, et al. "Mulberry Fruit Ameliorates Parkinson's-disease-related Pathology By Reducing Α-synuclein and Ubiquitin Levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid Model." The Journal of Nutritional Biochemistry, vol. 39, 2017, pp. 15-21.
Gu PS, Moon M, Choi JG, et al. Mulberry fruit ameliorates Parkinson's-disease-related pathology by reducing α-synuclein and ubiquitin levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model. J Nutr Biochem. 2017;39:15-21.
Gu, P. S., Moon, M., Choi, J. G., & Oh, M. S. (2017). Mulberry fruit ameliorates Parkinson's-disease-related pathology by reducing α-synuclein and ubiquitin levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model. The Journal of Nutritional Biochemistry, 39, 15-21. https://doi.org/10.1016/j.jnutbio.2016.08.014
Gu PS, et al. Mulberry Fruit Ameliorates Parkinson's-disease-related Pathology By Reducing Α-synuclein and Ubiquitin Levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid Model. J Nutr Biochem. 2017;39:15-21. PubMed PMID: 27741433.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mulberry fruit ameliorates Parkinson's-disease-related pathology by reducing α-synuclein and ubiquitin levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model. AU - Gu,Pil Sung, AU - Moon,Minho, AU - Choi,Jin Gyu, AU - Oh,Myung Sook, Y1 - 2016/09/22/ PY - 2016/02/01/received PY - 2016/08/03/revised PY - 2016/08/10/accepted PY - 2016/10/16/pubmed PY - 2018/1/18/medline PY - 2016/10/15/entrez KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - Mulberry fruit KW - Parkinson's disease KW - Probenecid KW - α-Synuclein SP - 15 EP - 21 JF - The Journal of nutritional biochemistry JO - J Nutr Biochem VL - 39 N2 - Mulberry fruit, which has been long used in traditional oriental medicine, was reported to ameliorate motor dysfunction and dopaminergic neuronal degeneration via antioxidant and antiapoptotic effects in an animal model of Parkinson's disease (PD). More than 95% of PD patients exhibit nonmotor problems such as olfactory dysfunction and gastrointestinal constipation, which are generally considered to be early symptoms of PD. However, few studies have actually examined potential drugs to treat early PD symptoms. The present study examined the protective effects of mulberry fruit extract (ME) against neurotoxicity in a 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) model of early PD. MPTP/p model was developed by systemic administration with MPTP (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. The behavioral studies showed that treatment of mice with ME significantly improved PD-related nonmotor symptoms as well as motor impairment, demonstrated by utilizing the olfactory, pole, rotarod and open field tests. In addition, immunohistochemical analysis indicated that ME exhibits the protective effects against dopaminergic neuronal damage induced by MPTP/p in the substantia nigra and striatum. Moreover, by using Western blot analysis, we found that treatment with ME inhibited the up-regulation of α-synuclein and ubiquitin, well known as composition of Lewy bodies in the substantia nigra and striatum of the MPTP/p mice. Taken together, these data suggest that ME may have therapeutic potential for preventing PD. SN - 1873-4847 UR - https://www.unboundmedicine.com/medline/citation/27741433/Mulberry_fruit_ameliorates_Parkinson's_disease_related_pathology_by_reducing_α_synuclein_and_ubiquitin_levels_in_a_1_methyl_4_phenyl_1236_tetrahydropyridine/probenecid_model_ DB - PRIME DP - Unbound Medicine ER -