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Effects of the Tibetan medicine Byur dMar Nyer lNga Ril Bu on Alzheimer's disease in mice models

Byur dMar Nyer lNga Ril Bu (BdNlRB) is a classic Tibetan medicine prescription for treating " white vein disease". Alzheimer's disease (AD) is a chronic degenerative disease of the central nervous system, characterized by distinct "white vein disease". In the absence of effe...

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Published in:Journal of ethnopharmacology 2022-01, Vol.283, p.114724-114724, Article 114724
Main Authors: Tsering, Jokyab, Chen, Qianqian, Li, Honghong, Han, Yanan, Wu, Jinpeng, Yin, Huijuan, Hu, Jiashen, Su, Siying, Shi, Xiafei, Hu, Xianda, Che, Bochen
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Chen, Qianqian
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description Byur dMar Nyer lNga Ril Bu (BdNlRB) is a classic Tibetan medicine prescription for treating " white vein disease". Alzheimer's disease (AD) is a chronic degenerative disease of the central nervous system, characterized by distinct "white vein disease". In the absence of effective drugs for AD, BdNlRB may be a possible treatment for AD. To verify the therapeutic effect and possible mechanism of the proved Tibetan medicine BdNlRB on Alzheimer's disease. 60 APP/PS1 double transgenic AD mice (Mt) and 60 Aß1-40 protein-induced AD mice (Mi) were divided into 3 groups according to the dose of BdNlRB: BdNlRB-100, BdNlRB-200 and BdNlRB-400, with 100, 200 and 400 mg/kg*weight, respectively. The mice were administrated by gavage for 8 weeks. The cognitive ability of mice was detected by Morris Water Maze, the expression of Aß protein, p-tau and microglia was detected by immunofluorescent staining, the protein expression in the hippocampus was detected by proteomics, and the abundance of fecal intestinal flora was detected by 16S RNA. The learning ability and memory ability of Mi mice were significantly improved after BdNlRB administration. The learning ability of Mt mice was significantly improved, while the memory ability was not improved after BdNlRB administration. After the treatment with low and medium doses of BdNlRB, the expression of p-tau decreased significantly (the rate of decrease in BdNlRB-100 and BdNlRB-200 groups was 8.05% and 12.7%, respectively), and the number of microglia increased (39.3% and 31.6%, respectively). BdNlRB significantly affected the protein expression in the hippocampus of Mt mice. 382 proteins in different expression in all three groups mainly involved in amino acid synthesis, fatty acid degradation, glutamine metabolism, synaptic vesicular cycle and oxidative phosphorylation, PPAR signaling pathway and Fc gamma-mediated phagocytosis were activated. Meanwhile, the administration of BdNlRB can regulate the intestinal flora of Mt mice, which reduces the abundance of Muribaculum and uncultured bacteroidales bacterium, and improves the abundance of Ruminococcus-1 and Ruminiclostridium-9. The oral administration of BdNlRB significantly improved the cognitive ability of AD mice, and neuroinflammation and intestinal flora regulation were the possible mechanisms. [Display omitted] •Two animal models of Alzheimer's disease were used to study the drug on gut flora.•BDNLRB can effectively improve the learning ability of the two AD models.•P-Ta
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Alzheimer's disease (AD) is a chronic degenerative disease of the central nervous system, characterized by distinct "white vein disease". In the absence of effective drugs for AD, BdNlRB may be a possible treatment for AD. To verify the therapeutic effect and possible mechanism of the proved Tibetan medicine BdNlRB on Alzheimer's disease. 60 APP/PS1 double transgenic AD mice (Mt) and 60 Aß1-40 protein-induced AD mice (Mi) were divided into 3 groups according to the dose of BdNlRB: BdNlRB-100, BdNlRB-200 and BdNlRB-400, with 100, 200 and 400 mg/kg*weight, respectively. The mice were administrated by gavage for 8 weeks. The cognitive ability of mice was detected by Morris Water Maze, the expression of Aß protein, p-tau and microglia was detected by immunofluorescent staining, the protein expression in the hippocampus was detected by proteomics, and the abundance of fecal intestinal flora was detected by 16S RNA. The learning ability and memory ability of Mi mice were significantly improved after BdNlRB administration. The learning ability of Mt mice was significantly improved, while the memory ability was not improved after BdNlRB administration. After the treatment with low and medium doses of BdNlRB, the expression of p-tau decreased significantly (the rate of decrease in BdNlRB-100 and BdNlRB-200 groups was 8.05% and 12.7%, respectively), and the number of microglia increased (39.3% and 31.6%, respectively). BdNlRB significantly affected the protein expression in the hippocampus of Mt mice. 382 proteins in different expression in all three groups mainly involved in amino acid synthesis, fatty acid degradation, glutamine metabolism, synaptic vesicular cycle and oxidative phosphorylation, PPAR signaling pathway and Fc gamma-mediated phagocytosis were activated. Meanwhile, the administration of BdNlRB can regulate the intestinal flora of Mt mice, which reduces the abundance of Muribaculum and uncultured bacteroidales bacterium, and improves the abundance of Ruminococcus-1 and Ruminiclostridium-9. The oral administration of BdNlRB significantly improved the cognitive ability of AD mice, and neuroinflammation and intestinal flora regulation were the possible mechanisms. [Display omitted] •Two animal models of Alzheimer's disease were used to study the drug on gut flora.•BDNLRB can effectively improve the learning ability of the two AD models.•P-Tau decreased and microglia increased significantly after BDNLRB administration.•Muribaculum, Ruminococcus-1 and Ruminiclostridium-9 were affected by BdNlRB.</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2021.114724</identifier><identifier>PMID: 34627984</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Alzheimer Disease - drug therapy ; Alzheimer Disease - physiopathology ; Alzheimer's disease ; Animals ; Aß plaqhe ; Byur dMar Nyer lNga Ril Bu ; Cognition - drug effects ; Cognitive Dysfunction - drug therapy ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Gastrointestinal Microbiome - drug effects ; Intestinal flora ; Male ; Maze Learning - drug effects ; Medicine, Tibetan Traditional - methods ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuroinflammatory Diseases - drug therapy ; Plant Extracts - administration &amp; dosage ; Plant Extracts - pharmacology ; Proteomics</subject><ispartof>Journal of ethnopharmacology, 2022-01, Vol.283, p.114724-114724, Article 114724</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-17b5367539e792e9d24541e1fa9d56986c4afdc1b628f74e10f506974429552f3</citedby><cites>FETCH-LOGICAL-c353t-17b5367539e792e9d24541e1fa9d56986c4afdc1b628f74e10f506974429552f3</cites><orcidid>0000-0002-4821-7562</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34627984$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsering, Jokyab</creatorcontrib><creatorcontrib>Chen, Qianqian</creatorcontrib><creatorcontrib>Li, Honghong</creatorcontrib><creatorcontrib>Han, Yanan</creatorcontrib><creatorcontrib>Wu, Jinpeng</creatorcontrib><creatorcontrib>Yin, Huijuan</creatorcontrib><creatorcontrib>Hu, Jiashen</creatorcontrib><creatorcontrib>Su, Siying</creatorcontrib><creatorcontrib>Shi, Xiafei</creatorcontrib><creatorcontrib>Hu, Xianda</creatorcontrib><creatorcontrib>Che, Bochen</creatorcontrib><title>Effects of the Tibetan medicine Byur dMar Nyer lNga Ril Bu on Alzheimer's disease in mice models</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>Byur dMar Nyer lNga Ril Bu (BdNlRB) is a classic Tibetan medicine prescription for treating " white vein disease". Alzheimer's disease (AD) is a chronic degenerative disease of the central nervous system, characterized by distinct "white vein disease". In the absence of effective drugs for AD, BdNlRB may be a possible treatment for AD. To verify the therapeutic effect and possible mechanism of the proved Tibetan medicine BdNlRB on Alzheimer's disease. 60 APP/PS1 double transgenic AD mice (Mt) and 60 Aß1-40 protein-induced AD mice (Mi) were divided into 3 groups according to the dose of BdNlRB: BdNlRB-100, BdNlRB-200 and BdNlRB-400, with 100, 200 and 400 mg/kg*weight, respectively. The mice were administrated by gavage for 8 weeks. The cognitive ability of mice was detected by Morris Water Maze, the expression of Aß protein, p-tau and microglia was detected by immunofluorescent staining, the protein expression in the hippocampus was detected by proteomics, and the abundance of fecal intestinal flora was detected by 16S RNA. The learning ability and memory ability of Mi mice were significantly improved after BdNlRB administration. The learning ability of Mt mice was significantly improved, while the memory ability was not improved after BdNlRB administration. After the treatment with low and medium doses of BdNlRB, the expression of p-tau decreased significantly (the rate of decrease in BdNlRB-100 and BdNlRB-200 groups was 8.05% and 12.7%, respectively), and the number of microglia increased (39.3% and 31.6%, respectively). BdNlRB significantly affected the protein expression in the hippocampus of Mt mice. 382 proteins in different expression in all three groups mainly involved in amino acid synthesis, fatty acid degradation, glutamine metabolism, synaptic vesicular cycle and oxidative phosphorylation, PPAR signaling pathway and Fc gamma-mediated phagocytosis were activated. Meanwhile, the administration of BdNlRB can regulate the intestinal flora of Mt mice, which reduces the abundance of Muribaculum and uncultured bacteroidales bacterium, and improves the abundance of Ruminococcus-1 and Ruminiclostridium-9. The oral administration of BdNlRB significantly improved the cognitive ability of AD mice, and neuroinflammation and intestinal flora regulation were the possible mechanisms. [Display omitted] •Two animal models of Alzheimer's disease were used to study the drug on gut flora.•BDNLRB can effectively improve the learning ability of the two AD models.•P-Tau decreased and microglia increased significantly after BDNLRB administration.•Muribaculum, Ruminococcus-1 and Ruminiclostridium-9 were affected by BdNlRB.</description><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - physiopathology</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Aß plaqhe</subject><subject>Byur dMar Nyer lNga Ril Bu</subject><subject>Cognition - drug effects</subject><subject>Cognitive Dysfunction - drug therapy</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Gastrointestinal Microbiome - drug effects</subject><subject>Intestinal flora</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>Medicine, Tibetan Traditional - methods</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Neuroinflammatory Diseases - drug therapy</subject><subject>Plant Extracts - administration &amp; 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dosage</topic><topic>Plant Extracts - pharmacology</topic><topic>Proteomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsering, Jokyab</creatorcontrib><creatorcontrib>Chen, Qianqian</creatorcontrib><creatorcontrib>Li, Honghong</creatorcontrib><creatorcontrib>Han, Yanan</creatorcontrib><creatorcontrib>Wu, Jinpeng</creatorcontrib><creatorcontrib>Yin, Huijuan</creatorcontrib><creatorcontrib>Hu, Jiashen</creatorcontrib><creatorcontrib>Su, Siying</creatorcontrib><creatorcontrib>Shi, Xiafei</creatorcontrib><creatorcontrib>Hu, Xianda</creatorcontrib><creatorcontrib>Che, Bochen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsering, Jokyab</au><au>Chen, Qianqian</au><au>Li, Honghong</au><au>Han, Yanan</au><au>Wu, Jinpeng</au><au>Yin, Huijuan</au><au>Hu, Jiashen</au><au>Su, Siying</au><au>Shi, Xiafei</au><au>Hu, Xianda</au><au>Che, Bochen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of the Tibetan medicine Byur dMar Nyer lNga Ril Bu on Alzheimer's disease in mice models</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2022-01-30</date><risdate>2022</risdate><volume>283</volume><spage>114724</spage><epage>114724</epage><pages>114724-114724</pages><artnum>114724</artnum><issn>0378-8741</issn><eissn>1872-7573</eissn><abstract>Byur dMar Nyer lNga Ril Bu (BdNlRB) is a classic Tibetan medicine prescription for treating " white vein disease". Alzheimer's disease (AD) is a chronic degenerative disease of the central nervous system, characterized by distinct "white vein disease". In the absence of effective drugs for AD, BdNlRB may be a possible treatment for AD. To verify the therapeutic effect and possible mechanism of the proved Tibetan medicine BdNlRB on Alzheimer's disease. 60 APP/PS1 double transgenic AD mice (Mt) and 60 Aß1-40 protein-induced AD mice (Mi) were divided into 3 groups according to the dose of BdNlRB: BdNlRB-100, BdNlRB-200 and BdNlRB-400, with 100, 200 and 400 mg/kg*weight, respectively. The mice were administrated by gavage for 8 weeks. The cognitive ability of mice was detected by Morris Water Maze, the expression of Aß protein, p-tau and microglia was detected by immunofluorescent staining, the protein expression in the hippocampus was detected by proteomics, and the abundance of fecal intestinal flora was detected by 16S RNA. The learning ability and memory ability of Mi mice were significantly improved after BdNlRB administration. The learning ability of Mt mice was significantly improved, while the memory ability was not improved after BdNlRB administration. After the treatment with low and medium doses of BdNlRB, the expression of p-tau decreased significantly (the rate of decrease in BdNlRB-100 and BdNlRB-200 groups was 8.05% and 12.7%, respectively), and the number of microglia increased (39.3% and 31.6%, respectively). BdNlRB significantly affected the protein expression in the hippocampus of Mt mice. 382 proteins in different expression in all three groups mainly involved in amino acid synthesis, fatty acid degradation, glutamine metabolism, synaptic vesicular cycle and oxidative phosphorylation, PPAR signaling pathway and Fc gamma-mediated phagocytosis were activated. Meanwhile, the administration of BdNlRB can regulate the intestinal flora of Mt mice, which reduces the abundance of Muribaculum and uncultured bacteroidales bacterium, and improves the abundance of Ruminococcus-1 and Ruminiclostridium-9. The oral administration of BdNlRB significantly improved the cognitive ability of AD mice, and neuroinflammation and intestinal flora regulation were the possible mechanisms. [Display omitted] •Two animal models of Alzheimer's disease were used to study the drug on gut flora.•BDNLRB can effectively improve the learning ability of the two AD models.•P-Tau decreased and microglia increased significantly after BDNLRB administration.•Muribaculum, Ruminococcus-1 and Ruminiclostridium-9 were affected by BdNlRB.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>34627984</pmid><doi>10.1016/j.jep.2021.114724</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-4821-7562</orcidid></addata></record>
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subjects Alzheimer Disease - drug therapy
Alzheimer Disease - physiopathology
Alzheimer's disease
Animals
Aß plaqhe
Byur dMar Nyer lNga Ril Bu
Cognition - drug effects
Cognitive Dysfunction - drug therapy
Disease Models, Animal
Dose-Response Relationship, Drug
Gastrointestinal Microbiome - drug effects
Intestinal flora
Male
Maze Learning - drug effects
Medicine, Tibetan Traditional - methods
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neuroinflammatory Diseases - drug therapy
Plant Extracts - administration & dosage
Plant Extracts - pharmacology
Proteomics
title Effects of the Tibetan medicine Byur dMar Nyer lNga Ril Bu on Alzheimer's disease in mice models
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