Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway

Objective. Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model o...

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Veröffentlicht in:Evidence-based complementary and alternative medicine 2020, Vol.2020 (2020), p.1-11
Hauptverfasser: Yu, Gu-Ran, Xie, Dao-Jun, Chen, Huai-Zhen, Jin, Shan, Cui, Shen-Wei, Li, Liang-Yong, Tang, Lu-Lu, Zhang, Jing, Yang, Wen-Ming
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container_end_page 11
container_issue 2020
container_start_page 1
container_title Evidence-based complementary and alternative medicine
container_volume 2020
creator Yu, Gu-Ran
Xie, Dao-Jun
Chen, Huai-Zhen
Jin, Shan
Cui, Shen-Wei
Li, Liang-Yong
Tang, Lu-Lu
Zhang, Jing
Yang, Wen-Ming
description Objective. Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. Methods. Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. Results. Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. Conclusion. Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.
doi_str_mv 10.1155/2020/3183714
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Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. Methods. Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. Results. Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. Conclusion. Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2020/3183714</identifier><identifier>PMID: 33456485</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Alanine ; Alanine transaminase ; Animals ; Apoptosis ; Aspartate transaminase ; Autophagy ; Bilirubin ; Chinese medicine ; Disease ; Drug dosages ; Enzyme-linked immunosorbent assay ; Ethics ; Fluorescence microscopy ; Gene expression ; Mitochondria ; Mitophagy ; Mutation ; Neuroprotection ; Oxidative stress ; Parkin protein ; Polymerase chain reaction ; PTEN-induced putative kinase ; Reverse transcription ; Transaminase ; Transmission electron microscopy ; Western blotting ; Wilson's disease</subject><ispartof>Evidence-based complementary and alternative medicine, 2020, Vol.2020 (2020), p.1-11</ispartof><rights>Copyright © 2020 Jing Zhang et al.</rights><rights>Copyright © 2020 Jing Zhang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Jing Zhang et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-83d177c70c81800b2d447d6d21046860e46bb6d0b430b6828ba6b248102378bf3</citedby><cites>FETCH-LOGICAL-c471t-83d177c70c81800b2d447d6d21046860e46bb6d0b430b6828ba6b248102378bf3</cites><orcidid>0000-0002-8333-8554 ; 0000-0003-4237-4855 ; 0000-0002-9356-8695 ; 0000-0001-8154-5894 ; 0000-0002-4273-6222 ; 0000-0001-8509-2140 ; 0000-0003-4102-938X ; 0000-0003-2362-1363 ; 0000-0001-8163-7318</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787754/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787754/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,4025,27925,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33456485$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chen, Xiaojia</contributor><contributor>Xiaojia Chen</contributor><creatorcontrib>Yu, Gu-Ran</creatorcontrib><creatorcontrib>Xie, Dao-Jun</creatorcontrib><creatorcontrib>Chen, Huai-Zhen</creatorcontrib><creatorcontrib>Jin, Shan</creatorcontrib><creatorcontrib>Cui, Shen-Wei</creatorcontrib><creatorcontrib>Li, Liang-Yong</creatorcontrib><creatorcontrib>Tang, Lu-Lu</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Yang, Wen-Ming</creatorcontrib><title>Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway</title><title>Evidence-based complementary and alternative medicine</title><addtitle>Evid Based Complement Alternat Med</addtitle><description>Objective. Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. Methods. Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. Results. Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. Conclusion. 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Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. Methods. Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. Results. Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. Conclusion. Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>33456485</pmid><doi>10.1155/2020/3183714</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8333-8554</orcidid><orcidid>https://orcid.org/0000-0003-4237-4855</orcidid><orcidid>https://orcid.org/0000-0002-9356-8695</orcidid><orcidid>https://orcid.org/0000-0001-8154-5894</orcidid><orcidid>https://orcid.org/0000-0002-4273-6222</orcidid><orcidid>https://orcid.org/0000-0001-8509-2140</orcidid><orcidid>https://orcid.org/0000-0003-4102-938X</orcidid><orcidid>https://orcid.org/0000-0003-2362-1363</orcidid><orcidid>https://orcid.org/0000-0001-8163-7318</orcidid><oa>free_for_read</oa></addata></record>
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subjects Alanine
Alanine transaminase
Animals
Apoptosis
Aspartate transaminase
Autophagy
Bilirubin
Chinese medicine
Disease
Drug dosages
Enzyme-linked immunosorbent assay
Ethics
Fluorescence microscopy
Gene expression
Mitochondria
Mitophagy
Mutation
Neuroprotection
Oxidative stress
Parkin protein
Polymerase chain reaction
PTEN-induced putative kinase
Reverse transcription
Transaminase
Transmission electron microscopy
Western blotting
Wilson's disease
title Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway
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