Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats
Background: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor Aβ42 which was the marker of Alzheimer’s disease. In addition, th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00334/full |
| _version_ | 1818560369870766080 |
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| author | Qingjie Chen Qingjie Chen Ran Mo Ninghua Wu Xin Zou Cai Shi Jing Gong Jingbin Li Ke Fang Dingkun Wang Deshen Yang Kaifu Wang Juan Chen Juan Chen |
| author_facet | Qingjie Chen Qingjie Chen Ran Mo Ninghua Wu Xin Zou Cai Shi Jing Gong Jingbin Li Ke Fang Dingkun Wang Deshen Yang Kaifu Wang Juan Chen Juan Chen |
| author_sort | Qingjie Chen |
| collection | DOAJ |
| description | Background: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor Aβ42 which was the marker of Alzheimer’s disease. In addition, the impairment of memory in diabetes mellitus was also correlated predominantly with uptake/metabolism of glucose in medial prefrontal cortex (mPFC). Previously, anti-inflammation and hypoglycemic effects of berberine (BBr) have been described in peripheral tissues. For better understanding the effects of BBr on cognitive action in diabetics, we investigated the functions of BBr involved in anti-inflammation and ameliorating insulin resistance in prefrontal cortex of diabetic rats.Methods: Intragastric administration of BBr (187.5 mg/Kg/d) was used in diabetic rats. Fear-condition assay was applied for cognitive assessment, and relative protein expressions were detected by western-blot. The glucose uptake in prefrontal cortex of diabetic rats was tested by Positron-Emission Tomography imaging. The levels of inflammation mediators were determined by commercial ELISA kits.Results: The inflammation mediator release and insulin resistance in the mPFC of diabetic rats was inhibited by BBr. The activation of PI3K/Akt/mTOR and MAPK signaling pathway, as well as two novel isoforms PKCη and PKC𝜀 and the translocation of NF-κB in neuron were also down-regulated by BBr; furthermore, the neuron specific glucose transporter GLUT3 was remarkably augmented by 2–3 times when compared with diabetic group; meanwhile, BBr also promoted glucose uptake in the brain. Additionally BBr decreased the expressions of amyloid precursor protein and BACE-1, and the production of oligomeric Aβ42. Finally, it accelerates the reinforcement of the information and ameliorates cognitive impairment.Conclusion: BBr inhibited the activation of inflammation pathway and insulin resistance in the mPFC of diabetic rats. Finally, it improved the lesion of cognition in diabetic rats. |
| first_indexed | 2024-12-14T00:37:38Z |
| format | Article |
| id | doaj.art-a82c979663fb429ab258fdabca306d74 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T00:37:38Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-a82c979663fb429ab258fdabca306d742022-12-21T23:24:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-06-01810.3389/fphar.2017.00334259304Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM RatsQingjie Chen0Qingjie Chen1Ran Mo2Ninghua Wu3Xin Zou4Cai Shi5Jing Gong6Jingbin Li7Ke Fang8Dingkun Wang9Deshen Yang10Kaifu Wang11Juan Chen12Juan Chen13Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaHubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and TechnologyXianning, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, ChinaInstitute for Brain Research, Huazhong University of Science and TechnologyWuhan, ChinaBackground: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor Aβ42 which was the marker of Alzheimer’s disease. In addition, the impairment of memory in diabetes mellitus was also correlated predominantly with uptake/metabolism of glucose in medial prefrontal cortex (mPFC). Previously, anti-inflammation and hypoglycemic effects of berberine (BBr) have been described in peripheral tissues. For better understanding the effects of BBr on cognitive action in diabetics, we investigated the functions of BBr involved in anti-inflammation and ameliorating insulin resistance in prefrontal cortex of diabetic rats.Methods: Intragastric administration of BBr (187.5 mg/Kg/d) was used in diabetic rats. Fear-condition assay was applied for cognitive assessment, and relative protein expressions were detected by western-blot. The glucose uptake in prefrontal cortex of diabetic rats was tested by Positron-Emission Tomography imaging. The levels of inflammation mediators were determined by commercial ELISA kits.Results: The inflammation mediator release and insulin resistance in the mPFC of diabetic rats was inhibited by BBr. The activation of PI3K/Akt/mTOR and MAPK signaling pathway, as well as two novel isoforms PKCη and PKC𝜀 and the translocation of NF-κB in neuron were also down-regulated by BBr; furthermore, the neuron specific glucose transporter GLUT3 was remarkably augmented by 2–3 times when compared with diabetic group; meanwhile, BBr also promoted glucose uptake in the brain. Additionally BBr decreased the expressions of amyloid precursor protein and BACE-1, and the production of oligomeric Aβ42. Finally, it accelerates the reinforcement of the information and ameliorates cognitive impairment.Conclusion: BBr inhibited the activation of inflammation pathway and insulin resistance in the mPFC of diabetic rats. Finally, it improved the lesion of cognition in diabetic rats.http://journal.frontiersin.org/article/10.3389/fphar.2017.00334/fullberberinecognitiveinflammationinsulinmedial prefrontal cortexneuron and astrocyte |
| spellingShingle | Qingjie Chen Qingjie Chen Ran Mo Ninghua Wu Xin Zou Cai Shi Jing Gong Jingbin Li Ke Fang Dingkun Wang Deshen Yang Kaifu Wang Juan Chen Juan Chen Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats Frontiers in Pharmacology berberine cognitive inflammation insulin medial prefrontal cortex neuron and astrocyte |
| title | Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats |
| title_full | Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats |
| title_fullStr | Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats |
| title_full_unstemmed | Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats |
| title_short | Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats |
| title_sort | berberine ameliorates diabetes associated cognitive decline through modulation of aberrant inflammation response and insulin signaling pathway in dm rats |
| topic | berberine cognitive inflammation insulin medial prefrontal cortex neuron and astrocyte |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00334/full |
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