Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity
Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platel...
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| Veröffentlicht in: | Free radical biology & medicine 2019-01, Vol.130, p.196-205 |
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| creator | Paul, Manoj Hemshekhar, Mahadevappa Kemparaju, Kempaiah Girish, Kesturu S. |
| description | Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platelet hyper-reactivity and apoptosis during DM is accounted for the accumulated reactive oxygen species (ROS) due to increased aldose reductase (AR) and NADPH oxidase (NOX) activities. Considering aspirin insensitivity in DM patients, new therapies targeting the underlying mechanism is urgently warranted. Berberine, a benzylisoquinoline alkaloids, from Chinese folk medicine has been demonstrated with several anti-diabetic effects. Therefore, we evaluated whether berberine inhibits high glucose potentiated platelet aggregation, apoptosis and further evaluated the mechanism of its action in platelets. Berberine was found to inhibit platelet aggregation, superoxide production via modulating AR, NOX, and glutathione reductase activities in high glucose (HG) treated platelets. Correlated with this, berberine inhibited, calcium release, ERK activation, α- and dense granule release and platelet adhesive properties. In addition, berberine inhibited p38-p53 mediated BAX activation, mitochondrial dysfunction and platelet apoptosis induced by HG. The platelet protective effect of berberine by inhibiting AR and NOX in high glucose-treated platelets suggest that berberine could be developed as a potential therapeutic molecule in the treating pathologies associated with DM.
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•Berberine (BB) inhibits aldose reductase (AR) and NADPH oxidase in platelets.•BB inhibits AR-mediated O2•− production in high glucose (HG)-treated platelets.•BB attenuates ROS-mediated p38-p53 activation and platelet apoptosis during HG.•BB inhibits HG-primed Ca2+ release, α/dense granule secretion, and platelet aggregation. |
| doi_str_mv | 10.1016/j.freeradbiomed.2018.10.453 |
| format | Article |
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[Display omitted]
•Berberine (BB) inhibits aldose reductase (AR) and NADPH oxidase in platelets.•BB inhibits AR-mediated O2•− production in high glucose (HG)-treated platelets.•BB attenuates ROS-mediated p38-p53 activation and platelet apoptosis during HG.•BB inhibits HG-primed Ca2+ release, α/dense granule secretion, and platelet aggregation.</description><identifier>ISSN: 0891-5849</identifier><identifier>EISSN: 1873-4596</identifier><identifier>DOI: 10.1016/j.freeradbiomed.2018.10.453</identifier><identifier>PMID: 30391673</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aldehyde Reductase - metabolism ; Antioxidants - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Arterial Occlusive Diseases - drug therapy ; Berberine ; Berberine - pharmacology ; Blood Platelets - drug effects ; Blood Platelets - physiology ; Cells, Cultured ; Diabetes mellitus ; Diabetes Mellitus - drug therapy ; Glucose - metabolism ; Humans ; Medicine, Chinese Traditional ; NADPH Oxidases - metabolism ; Oxidation-Reduction ; Oxidative Stress ; Platelet aggregation ; Platelet Aggregation - drug effects ; Platelets ; Reactive Oxygen Species - metabolism ; Signal Transduction</subject><ispartof>Free radical biology & medicine, 2019-01, Vol.130, p.196-205</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-e971e3c1ff196b7a396b7bb58b9c2871d7dcbb4df40e9468e73f58f409b438923</citedby><cites>FETCH-LOGICAL-c449t-e971e3c1ff196b7a396b7bb58b9c2871d7dcbb4df40e9468e73f58f409b438923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0891584918311390$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30391673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Paul, Manoj</creatorcontrib><creatorcontrib>Hemshekhar, Mahadevappa</creatorcontrib><creatorcontrib>Kemparaju, Kempaiah</creatorcontrib><creatorcontrib>Girish, Kesturu S.</creatorcontrib><title>Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity</title><title>Free radical biology & medicine</title><addtitle>Free Radic Biol Med</addtitle><description>Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platelet hyper-reactivity and apoptosis during DM is accounted for the accumulated reactive oxygen species (ROS) due to increased aldose reductase (AR) and NADPH oxidase (NOX) activities. Considering aspirin insensitivity in DM patients, new therapies targeting the underlying mechanism is urgently warranted. Berberine, a benzylisoquinoline alkaloids, from Chinese folk medicine has been demonstrated with several anti-diabetic effects. Therefore, we evaluated whether berberine inhibits high glucose potentiated platelet aggregation, apoptosis and further evaluated the mechanism of its action in platelets. Berberine was found to inhibit platelet aggregation, superoxide production via modulating AR, NOX, and glutathione reductase activities in high glucose (HG) treated platelets. Correlated with this, berberine inhibited, calcium release, ERK activation, α- and dense granule release and platelet adhesive properties. In addition, berberine inhibited p38-p53 mediated BAX activation, mitochondrial dysfunction and platelet apoptosis induced by HG. The platelet protective effect of berberine by inhibiting AR and NOX in high glucose-treated platelets suggest that berberine could be developed as a potential therapeutic molecule in the treating pathologies associated with DM.
[Display omitted]
•Berberine (BB) inhibits aldose reductase (AR) and NADPH oxidase in platelets.•BB inhibits AR-mediated O2•− production in high glucose (HG)-treated platelets.•BB attenuates ROS-mediated p38-p53 activation and platelet apoptosis during HG.•BB inhibits HG-primed Ca2+ release, α/dense granule secretion, and platelet aggregation.</description><subject>Aldehyde Reductase - metabolism</subject><subject>Antioxidants - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Arterial Occlusive Diseases - drug therapy</subject><subject>Berberine</subject><subject>Berberine - pharmacology</subject><subject>Blood Platelets - drug effects</subject><subject>Blood Platelets - physiology</subject><subject>Cells, Cultured</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus - drug therapy</subject><subject>Glucose - metabolism</subject><subject>Humans</subject><subject>Medicine, Chinese Traditional</subject><subject>NADPH Oxidases - metabolism</subject><subject>Oxidation-Reduction</subject><subject>Oxidative Stress</subject><subject>Platelet aggregation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelets</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Signal Transduction</subject><issn>0891-5849</issn><issn>1873-4596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9u1DAQxi0EokvhFZAlLlyy2LGT2OJUSqFIFXCAs-U_k9SrJA62U3UfgbfGYdsDNy4ej7_fzMjzIfSGkj0ltH132PcRIGpnfJjA7WtCRVH2vGFP0I6KjlW8ke1TtCNC0qoRXJ6hFykdCCGFEc_RGSNM0rZjO_T7A0QD0c-AJ5_9oDMkfOuHWzyMqw0JqiVkmLMvgsPLWMIIGethiFBgH2asZ4f1EpYckk_YHPEU3FpAPw9Yj670wBHcarMutw3-evHx-zUO9979fbHZ3_l8fIme9XpM8OohnqOfn65-XF5XN98-f7m8uKks5zJXIDsKzNK-p7I1nWbbaUwjjLS16KjrnDWGu54TkLwV0LG-ESWThjMha3aO3p76LjH8WiFlNflkYRz1DGFNqqaMkEa0NSvo-xNqY0gpQq-W6Ccdj4oStXmhDuofL9TmxSaWPZfq1w-DVrNpj7WPyy_A1QmA8t07D1El62G24HwEm5UL_r8G_QFa8KX0</recordid><startdate>201901</startdate><enddate>201901</enddate><creator>Paul, Manoj</creator><creator>Hemshekhar, Mahadevappa</creator><creator>Kemparaju, Kempaiah</creator><creator>Girish, Kesturu S.</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>201901</creationdate><title>Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity</title><author>Paul, Manoj ; Hemshekhar, Mahadevappa ; Kemparaju, Kempaiah ; Girish, Kesturu S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-e971e3c1ff196b7a396b7bb58b9c2871d7dcbb4df40e9468e73f58f409b438923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aldehyde Reductase - metabolism</topic><topic>Antioxidants - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Arterial Occlusive Diseases - drug therapy</topic><topic>Berberine</topic><topic>Berberine - pharmacology</topic><topic>Blood Platelets - drug effects</topic><topic>Blood Platelets - physiology</topic><topic>Cells, Cultured</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus - drug therapy</topic><topic>Glucose - metabolism</topic><topic>Humans</topic><topic>Medicine, Chinese Traditional</topic><topic>NADPH Oxidases - metabolism</topic><topic>Oxidation-Reduction</topic><topic>Oxidative Stress</topic><topic>Platelet aggregation</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelets</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paul, Manoj</creatorcontrib><creatorcontrib>Hemshekhar, Mahadevappa</creatorcontrib><creatorcontrib>Kemparaju, Kempaiah</creatorcontrib><creatorcontrib>Girish, Kesturu S.</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>Free radical biology & medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paul, Manoj</au><au>Hemshekhar, Mahadevappa</au><au>Kemparaju, Kempaiah</au><au>Girish, Kesturu S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity</atitle><jtitle>Free radical biology & medicine</jtitle><addtitle>Free Radic Biol Med</addtitle><date>2019-01</date><risdate>2019</risdate><volume>130</volume><spage>196</spage><epage>205</epage><pages>196-205</pages><issn>0891-5849</issn><eissn>1873-4596</eissn><abstract>Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platelet hyper-reactivity and apoptosis during DM is accounted for the accumulated reactive oxygen species (ROS) due to increased aldose reductase (AR) and NADPH oxidase (NOX) activities. Considering aspirin insensitivity in DM patients, new therapies targeting the underlying mechanism is urgently warranted. Berberine, a benzylisoquinoline alkaloids, from Chinese folk medicine has been demonstrated with several anti-diabetic effects. Therefore, we evaluated whether berberine inhibits high glucose potentiated platelet aggregation, apoptosis and further evaluated the mechanism of its action in platelets. Berberine was found to inhibit platelet aggregation, superoxide production via modulating AR, NOX, and glutathione reductase activities in high glucose (HG) treated platelets. Correlated with this, berberine inhibited, calcium release, ERK activation, α- and dense granule release and platelet adhesive properties. In addition, berberine inhibited p38-p53 mediated BAX activation, mitochondrial dysfunction and platelet apoptosis induced by HG. The platelet protective effect of berberine by inhibiting AR and NOX in high glucose-treated platelets suggest that berberine could be developed as a potential therapeutic molecule in the treating pathologies associated with DM.
[Display omitted]
•Berberine (BB) inhibits aldose reductase (AR) and NADPH oxidase in platelets.•BB inhibits AR-mediated O2•− production in high glucose (HG)-treated platelets.•BB attenuates ROS-mediated p38-p53 activation and platelet apoptosis during HG.•BB inhibits HG-primed Ca2+ release, α/dense granule secretion, and platelet aggregation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30391673</pmid><doi>10.1016/j.freeradbiomed.2018.10.453</doi><tpages>10</tpages></addata></record> |
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| subjects | Aldehyde Reductase - metabolism Antioxidants - pharmacology Apoptosis Apoptosis - drug effects Arterial Occlusive Diseases - drug therapy Berberine Berberine - pharmacology Blood Platelets - drug effects Blood Platelets - physiology Cells, Cultured Diabetes mellitus Diabetes Mellitus - drug therapy Glucose - metabolism Humans Medicine, Chinese Traditional NADPH Oxidases - metabolism Oxidation-Reduction Oxidative Stress Platelet aggregation Platelet Aggregation - drug effects Platelets Reactive Oxygen Species - metabolism Signal Transduction |
| title | Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity |
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