Bojungikgi-Tang, a Traditional Herbal Formula, Exerts Neuroprotective Effects and Ameliorates Memory Impairments in Alzheimer's Disease-Like Experimental Models
Bojungikgi-tang (BJIGT; Bu Zhong Yi Qi Tang in China, Hochuekkito in Japan) is a traditional Oriental herbal formula comprised of eight medicinal herbs that has long been used for the treatment of digestive disorders. A recent clinical study from South Korea reported that BJIGT-gamibang administrati...
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description | Bojungikgi-tang (BJIGT; Bu Zhong Yi Qi Tang in China, Hochuekkito in Japan) is a traditional Oriental herbal formula comprised of eight medicinal herbs that has long been used for the treatment of digestive disorders. A recent clinical study from South Korea reported that BJIGT-gamibang administration may be effective in treating dementia. We aimed to establish scientific evidence for the anti-dementia effects of BJIGT using in vitro and in vivo experimental models. We measured amyloid- β (Aβ) aggregation, β-secretase (BACE), and antioxidant activity in a cell free system. Neuroprotective effects were assessed using CCK-8. Imprinting control region (ICR) mice were divided into the following six groups: Normal control, Aβ-injected, Aβ-injection + oral BJIGT gavage (200, 400, or 800 mg/kg/day), and Aβ-injection + oral morin administration (10 mg/kg/day). Subsequently, behavioral evaluations were conducted and brain samples were collected from all the animals and assessed. BJIGT enhanced inhibition of Aβ aggregation and BACE activity in vivo, as well as antioxidant activity in in vitro, cell-free systems. BJIGT also exerted neuroprotective effects in a hydroperoxide (H₂O₂)-induced damaged HT22 hippocampal cell line model. In addition, BJIGT administration significantly ameliorated cognitive impairments in Aβ-injected mice, as assessed by the passive avoidance and Y-maze tests. Furthermore, BJIGT treatment suppressed Aβ aggregation and expression, as well as expression of Aβ, NeuN, and brain-derived neurotrophic factor (BDNF) in the hippocampi of Aβ-injected mice. Overall, our results demonstrate that, with further testing in clinical populations, BJIGT may have great utility for the treatment of dementia and especially Alzheimer's disease. |
doi_str_mv | 10.3390/nu10121952 |
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A recent clinical study from South Korea reported that BJIGT-gamibang administration may be effective in treating dementia. We aimed to establish scientific evidence for the anti-dementia effects of BJIGT using in vitro and in vivo experimental models. We measured amyloid- β (Aβ) aggregation, β-secretase (BACE), and antioxidant activity in a cell free system. Neuroprotective effects were assessed using CCK-8. Imprinting control region (ICR) mice were divided into the following six groups: Normal control, Aβ-injected, Aβ-injection + oral BJIGT gavage (200, 400, or 800 mg/kg/day), and Aβ-injection + oral morin administration (10 mg/kg/day). Subsequently, behavioral evaluations were conducted and brain samples were collected from all the animals and assessed. BJIGT enhanced inhibition of Aβ aggregation and BACE activity in vivo, as well as antioxidant activity in in vitro, cell-free systems. BJIGT also exerted neuroprotective effects in a hydroperoxide (H₂O₂)-induced damaged HT22 hippocampal cell line model. In addition, BJIGT administration significantly ameliorated cognitive impairments in Aβ-injected mice, as assessed by the passive avoidance and Y-maze tests. Furthermore, BJIGT treatment suppressed Aβ aggregation and expression, as well as expression of Aβ, NeuN, and brain-derived neurotrophic factor (BDNF) in the hippocampi of Aβ-injected mice. Overall, our results demonstrate that, with further testing in clinical populations, BJIGT may have great utility for the treatment of dementia and especially Alzheimer's disease.</description><identifier>ISSN: 2072-6643</identifier><identifier>EISSN: 2072-6643</identifier><identifier>DOI: 10.3390/nu10121952</identifier><identifier>PMID: 30544702</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alzheimer Disease - metabolism ; Alzheimer's disease ; Amyloid ; Animals ; antioxidant activity ; Antioxidants ; Behavior, Animal - drug effects ; brain ; Brain-derived neurotrophic factor ; Calibration ; cell free system ; Cell Line ; cell lines ; China ; Cholecystokinin ; Chromatography ; cognitive disorders ; Dementia ; Dementia disorders ; digestive system diseases ; Disease Models, Animal ; Drugs, Chinese Herbal - analysis ; Drugs, Chinese Herbal - chemistry ; Drugs, Chinese Herbal - pharmacology ; Enzymes ; Experiments ; Health services ; Herbal medicine ; Hippocampus ; Humans ; Hydrogen peroxide ; In vivo methods and tests ; Injection ; Japan ; Male ; Medicinal herbs ; medicinal plants ; Memory ; Memory - drug effects ; memory disorders ; Mice ; Mice, Inbred ICR ; Neuroprotection ; Neuroprotective Agents - analysis ; Neuroprotective Agents - chemistry ; Neuroprotective Agents - pharmacology ; neuroprotective effect ; Reagents ; Secretase ; South Korea ; β-Site APP-cleaving enzymes</subject><ispartof>Nutrients, 2018-12, Vol.10 (12), p.1952</ispartof><rights>2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 by the authors. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-9feb1a60541340566926981eebb7a513198696e5e378cc261ffbf9861190e0a03</citedby><cites>FETCH-LOGICAL-c505t-9feb1a60541340566926981eebb7a513198696e5e378cc261ffbf9861190e0a03</cites><orcidid>0000-0001-5152-9439 ; 0000-0003-0727-3864</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/PMC6316759/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316759/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30544702$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lim, Hye-Sun</creatorcontrib><creatorcontrib>Kim, Yu Jin</creatorcontrib><creatorcontrib>Sohn, Eunjin</creatorcontrib><creatorcontrib>Yoon, Jiyeon</creatorcontrib><creatorcontrib>Kim, Bu-Yeo</creatorcontrib><creatorcontrib>Jeong, Soo-Jin</creatorcontrib><title>Bojungikgi-Tang, a Traditional Herbal Formula, Exerts Neuroprotective Effects and Ameliorates Memory Impairments in Alzheimer's Disease-Like Experimental Models</title><title>Nutrients</title><addtitle>Nutrients</addtitle><description>Bojungikgi-tang (BJIGT; Bu Zhong Yi Qi Tang in China, Hochuekkito in Japan) is a traditional Oriental herbal formula comprised of eight medicinal herbs that has long been used for the treatment of digestive disorders. A recent clinical study from South Korea reported that BJIGT-gamibang administration may be effective in treating dementia. We aimed to establish scientific evidence for the anti-dementia effects of BJIGT using in vitro and in vivo experimental models. We measured amyloid- β (Aβ) aggregation, β-secretase (BACE), and antioxidant activity in a cell free system. Neuroprotective effects were assessed using CCK-8. Imprinting control region (ICR) mice were divided into the following six groups: Normal control, Aβ-injected, Aβ-injection + oral BJIGT gavage (200, 400, or 800 mg/kg/day), and Aβ-injection + oral morin administration (10 mg/kg/day). Subsequently, behavioral evaluations were conducted and brain samples were collected from all the animals and assessed. BJIGT enhanced inhibition of Aβ aggregation and BACE activity in vivo, as well as antioxidant activity in in vitro, cell-free systems. BJIGT also exerted neuroprotective effects in a hydroperoxide (H₂O₂)-induced damaged HT22 hippocampal cell line model. In addition, BJIGT administration significantly ameliorated cognitive impairments in Aβ-injected mice, as assessed by the passive avoidance and Y-maze tests. Furthermore, BJIGT treatment suppressed Aβ aggregation and expression, as well as expression of Aβ, NeuN, and brain-derived neurotrophic factor (BDNF) in the hippocampi of Aβ-injected mice. Overall, our results demonstrate that, with further testing in clinical populations, BJIGT may have great utility for the treatment of dementia and especially Alzheimer's disease.</description><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer's disease</subject><subject>Amyloid</subject><subject>Animals</subject><subject>antioxidant activity</subject><subject>Antioxidants</subject><subject>Behavior, Animal - drug effects</subject><subject>brain</subject><subject>Brain-derived neurotrophic factor</subject><subject>Calibration</subject><subject>cell free system</subject><subject>Cell Line</subject><subject>cell lines</subject><subject>China</subject><subject>Cholecystokinin</subject><subject>Chromatography</subject><subject>cognitive disorders</subject><subject>Dementia</subject><subject>Dementia disorders</subject><subject>digestive system diseases</subject><subject>Disease Models, Animal</subject><subject>Drugs, Chinese Herbal - analysis</subject><subject>Drugs, Chinese Herbal - chemistry</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Enzymes</subject><subject>Experiments</subject><subject>Health services</subject><subject>Herbal medicine</subject><subject>Hippocampus</subject><subject>Humans</subject><subject>Hydrogen peroxide</subject><subject>In vivo methods and tests</subject><subject>Injection</subject><subject>Japan</subject><subject>Male</subject><subject>Medicinal herbs</subject><subject>medicinal plants</subject><subject>Memory</subject><subject>Memory - drug effects</subject><subject>memory disorders</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - analysis</subject><subject>Neuroprotective Agents - chemistry</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>neuroprotective effect</subject><subject>Reagents</subject><subject>Secretase</subject><subject>South Korea</subject><subject>β-Site APP-cleaving enzymes</subject><issn>2072-6643</issn><issn>2072-6643</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFks1u1DAUhS0EolXphgdAlliAUAP-ie3xBmkoU1ppCpthbTmZm6mnjp3aSdXyNDwqHrWUwgZv7pX96fhc3YPQS0rec67JhzBRQhnVgj1B-4woVklZ86eP-j10mPOW7I4iSvLnaI8TUdeKsH3081PcTmHjLjeuWtmwOcIWr5Jdu9HFYD0-hdSUchJTP3l7hBc3kMaMv8KU4pDiCO3orgEvuq50GduwxvMevIvJjpDxOfQx3eKzfrAu9RAK4gKe-x8X4HpIbzL-7DLYDNXSXRaZmwGS23Hlz_O4Bp9foGed9RkO7-sB-n6yWB2fVstvX86O58uqFUSMle6goVaWuSiviZBSM6lnFKBplBWUUz2TWoIArmZtyyTtuqYrd5RqAsQSfoA-3ukOU9PDui0ekvVmKHZsujXROvP3S3AXZhOvjeRUKqGLwNt7gRSvJsij6V1uwXsbIE7ZMFYckJmsxf9RKpRUNaU7W6__QbdxSmUzhZKybJMJwQv17o5qU8w5QffgmxKzi4n5E5MCv3o86QP6OxT8Fx9SuTw</recordid><startdate>20181210</startdate><enddate>20181210</enddate><creator>Lim, Hye-Sun</creator><creator>Kim, Yu Jin</creator><creator>Sohn, Eunjin</creator><creator>Yoon, Jiyeon</creator><creator>Kim, Bu-Yeo</creator><creator>Jeong, Soo-Jin</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5152-9439</orcidid><orcidid>https://orcid.org/0000-0003-0727-3864</orcidid></search><sort><creationdate>20181210</creationdate><title>Bojungikgi-Tang, a Traditional Herbal Formula, Exerts Neuroprotective Effects and Ameliorates Memory Impairments in Alzheimer's Disease-Like Experimental Models</title><author>Lim, Hye-Sun ; Kim, Yu Jin ; Sohn, Eunjin ; Yoon, Jiyeon ; Kim, Bu-Yeo ; Jeong, Soo-Jin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-9feb1a60541340566926981eebb7a513198696e5e378cc261ffbf9861190e0a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer's disease</topic><topic>Amyloid</topic><topic>Animals</topic><topic>antioxidant activity</topic><topic>Antioxidants</topic><topic>Behavior, Animal - drug effects</topic><topic>brain</topic><topic>Brain-derived neurotrophic factor</topic><topic>Calibration</topic><topic>cell free system</topic><topic>Cell Line</topic><topic>cell lines</topic><topic>China</topic><topic>Cholecystokinin</topic><topic>Chromatography</topic><topic>cognitive disorders</topic><topic>Dementia</topic><topic>Dementia disorders</topic><topic>digestive system diseases</topic><topic>Disease Models, Animal</topic><topic>Drugs, Chinese Herbal - analysis</topic><topic>Drugs, Chinese Herbal - chemistry</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Enzymes</topic><topic>Experiments</topic><topic>Health services</topic><topic>Herbal medicine</topic><topic>Hippocampus</topic><topic>Humans</topic><topic>Hydrogen peroxide</topic><topic>In vivo methods and tests</topic><topic>Injection</topic><topic>Japan</topic><topic>Male</topic><topic>Medicinal herbs</topic><topic>medicinal plants</topic><topic>Memory</topic><topic>Memory - drug effects</topic><topic>memory disorders</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - analysis</topic><topic>Neuroprotective Agents - chemistry</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>neuroprotective effect</topic><topic>Reagents</topic><topic>Secretase</topic><topic>South Korea</topic><topic>β-Site APP-cleaving enzymes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lim, Hye-Sun</creatorcontrib><creatorcontrib>Kim, Yu Jin</creatorcontrib><creatorcontrib>Sohn, Eunjin</creatorcontrib><creatorcontrib>Yoon, Jiyeon</creatorcontrib><creatorcontrib>Kim, Bu-Yeo</creatorcontrib><creatorcontrib>Jeong, Soo-Jin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Physical Education Index</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nutrients</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lim, Hye-Sun</au><au>Kim, Yu Jin</au><au>Sohn, Eunjin</au><au>Yoon, Jiyeon</au><au>Kim, Bu-Yeo</au><au>Jeong, Soo-Jin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bojungikgi-Tang, a Traditional Herbal Formula, Exerts Neuroprotective Effects and Ameliorates Memory Impairments in Alzheimer's Disease-Like Experimental Models</atitle><jtitle>Nutrients</jtitle><addtitle>Nutrients</addtitle><date>2018-12-10</date><risdate>2018</risdate><volume>10</volume><issue>12</issue><spage>1952</spage><pages>1952-</pages><issn>2072-6643</issn><eissn>2072-6643</eissn><abstract>Bojungikgi-tang (BJIGT; Bu Zhong Yi Qi Tang in China, Hochuekkito in Japan) is a traditional Oriental herbal formula comprised of eight medicinal herbs that has long been used for the treatment of digestive disorders. A recent clinical study from South Korea reported that BJIGT-gamibang administration may be effective in treating dementia. We aimed to establish scientific evidence for the anti-dementia effects of BJIGT using in vitro and in vivo experimental models. We measured amyloid- β (Aβ) aggregation, β-secretase (BACE), and antioxidant activity in a cell free system. Neuroprotective effects were assessed using CCK-8. Imprinting control region (ICR) mice were divided into the following six groups: Normal control, Aβ-injected, Aβ-injection + oral BJIGT gavage (200, 400, or 800 mg/kg/day), and Aβ-injection + oral morin administration (10 mg/kg/day). Subsequently, behavioral evaluations were conducted and brain samples were collected from all the animals and assessed. BJIGT enhanced inhibition of Aβ aggregation and BACE activity in vivo, as well as antioxidant activity in in vitro, cell-free systems. BJIGT also exerted neuroprotective effects in a hydroperoxide (H₂O₂)-induced damaged HT22 hippocampal cell line model. In addition, BJIGT administration significantly ameliorated cognitive impairments in Aβ-injected mice, as assessed by the passive avoidance and Y-maze tests. Furthermore, BJIGT treatment suppressed Aβ aggregation and expression, as well as expression of Aβ, NeuN, and brain-derived neurotrophic factor (BDNF) in the hippocampi of Aβ-injected mice. Overall, our results demonstrate that, with further testing in clinical populations, BJIGT may have great utility for the treatment of dementia and especially Alzheimer's disease.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>30544702</pmid><doi>10.3390/nu10121952</doi><orcidid>https://orcid.org/0000-0001-5152-9439</orcidid><orcidid>https://orcid.org/0000-0003-0727-3864</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Alzheimer Disease - metabolism Alzheimer's disease Amyloid Animals antioxidant activity Antioxidants Behavior, Animal - drug effects brain Brain-derived neurotrophic factor Calibration cell free system Cell Line cell lines China Cholecystokinin Chromatography cognitive disorders Dementia Dementia disorders digestive system diseases Disease Models, Animal Drugs, Chinese Herbal - analysis Drugs, Chinese Herbal - chemistry Drugs, Chinese Herbal - pharmacology Enzymes Experiments Health services Herbal medicine Hippocampus Humans Hydrogen peroxide In vivo methods and tests Injection Japan Male Medicinal herbs medicinal plants Memory Memory - drug effects memory disorders Mice Mice, Inbred ICR Neuroprotection Neuroprotective Agents - analysis Neuroprotective Agents - chemistry Neuroprotective Agents - pharmacology neuroprotective effect Reagents Secretase South Korea β-Site APP-cleaving enzymes |
title | Bojungikgi-Tang, a Traditional Herbal Formula, Exerts Neuroprotective Effects and Ameliorates Memory Impairments in Alzheimer's Disease-Like Experimental Models |
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