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Piceatannol alleviates inflammation and oxidative stress via modulation of the Nrf2/HO-1 and NF-κB pathways in diabetic cardiomyopathy
Diabetic cardiomyopathy (DCM) is one of the leading causes of morbidity and mortality in diabetic patients. Piceatannol (PIC) has protective effects against cardiovascular disease; however, it remains unknown whether it also protects against DCM. A Cell Counting Kit-8 (CCK-8) assay was used to evalu...
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Published in: | Chemico-biological interactions 2019-09, Vol.310, p.108754-108754, Article 108754 |
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description | Diabetic cardiomyopathy (DCM) is one of the leading causes of morbidity and mortality in diabetic patients. Piceatannol (PIC) has protective effects against cardiovascular disease; however, it remains unknown whether it also protects against DCM. A Cell Counting Kit-8 (CCK-8) assay was used to evaluate the effects of PIC on the viability of high glucose (HG)-induced H9C2 cells. Protein expression and mRNA levels were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. In vivo, physical and biochemical analyses, together with transthoracic echocardiography and hemodynamic measurements, were used to detect the effects of PIC treatment on cardiac function in DCM rats. Reactive oxygen species production was determined using an ELISA kit, and inflammatory cytokines were detected by RT-PCR. Pathological changes were assessed by hematoxylin-eosin staining, immunohistochemical staining, and TUNEL staining. According to the results, PIC treatment improved cell viability and inhibited cell apoptosis in HG-induced H9C2 cardiac myoblasts. In addition, PIC not only attenuated the over-production of interleukin-6 (IL-6) (P |
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•PIC inhibits cell apoptosis by reducing oxidative stress and inflammation.•The pic-mediated suppression of NF-κB activation is dependent on Nrf2.•PIC improves the cardiac function of DCM rats.•PIC suppresses diabetes-induced cardiac oxidative stress and inflammation.•PIC can be a promising and safe agent for the treatment of DCM.</description><identifier>ISSN: 0009-2797</identifier><identifier>EISSN: 1872-7786</identifier><identifier>DOI: 10.1016/j.cbi.2019.108754</identifier><identifier>PMID: 31323227</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Cardiomyopathy ; Diabetic ; Inflammation ; Nrf-2/HO-1 ; Oxidative stress ; Piceatannol</subject><ispartof>Chemico-biological interactions, 2019-09, Vol.310, p.108754-108754, Article 108754</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-99f4401808a5d5ca5e84e6b76bab1267cf5c1809ea646b09683562eba01d54f73</citedby><cites>FETCH-LOGICAL-c353t-99f4401808a5d5ca5e84e6b76bab1267cf5c1809ea646b09683562eba01d54f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31323227$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Hao</creatorcontrib><creatorcontrib>Shi, Youyang</creatorcontrib><creatorcontrib>Wang, Xuliang</creatorcontrib><creatorcontrib>Li, Ping</creatorcontrib><creatorcontrib>Zhang, Songyue</creatorcontrib><creatorcontrib>Wu, Tingting</creatorcontrib><creatorcontrib>Yan, Yaoyao</creatorcontrib><creatorcontrib>Zhan, Yi</creatorcontrib><creatorcontrib>Ren, Yue</creatorcontrib><creatorcontrib>Rong, Xing</creatorcontrib><creatorcontrib>Xia, Tianhe</creatorcontrib><creatorcontrib>Chu, Maoping</creatorcontrib><creatorcontrib>Wu, Rongzhou</creatorcontrib><title>Piceatannol alleviates inflammation and oxidative stress via modulation of the Nrf2/HO-1 and NF-κB pathways in diabetic cardiomyopathy</title><title>Chemico-biological interactions</title><addtitle>Chem Biol Interact</addtitle><description>Diabetic cardiomyopathy (DCM) is one of the leading causes of morbidity and mortality in diabetic patients. Piceatannol (PIC) has protective effects against cardiovascular disease; however, it remains unknown whether it also protects against DCM. A Cell Counting Kit-8 (CCK-8) assay was used to evaluate the effects of PIC on the viability of high glucose (HG)-induced H9C2 cells. Protein expression and mRNA levels were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. In vivo, physical and biochemical analyses, together with transthoracic echocardiography and hemodynamic measurements, were used to detect the effects of PIC treatment on cardiac function in DCM rats. Reactive oxygen species production was determined using an ELISA kit, and inflammatory cytokines were detected by RT-PCR. Pathological changes were assessed by hematoxylin-eosin staining, immunohistochemical staining, and TUNEL staining. According to the results, PIC treatment improved cell viability and inhibited cell apoptosis in HG-induced H9C2 cardiac myoblasts. In addition, PIC not only attenuated the over-production of interleukin-6 (IL-6) (P < 0.05) and tumor necrosis factor alpha (TNF-α) (P < 0.05), but also improved the expression of nuclear factor E2-related factor 2 (Nrf2) (P < 0.05) and heme oxygenase-1 (HO-1) (P < 0.01). Importantly, knockdown of Nrf2 suppressed PIC-mediated activation of the Nrf2/HO-1 pathway and abolished its anti-inflammatory effects. In vivo, oral administration of PIC suppressed STZ-induced inflammation, oxidative stress hypertrophy, fibrosis(myocardial collagen volume fraction in 5 mg/kg and 10 mg/kg PIC group was decreased 25.83% and 55.61% compared with the DM group), and apoptosis(Caspase-3 level in 5 mg/kg and 10 mg/kg PIC group was decreased 13.21% and 33.91% compared with the DM group), thereby relieving cardiac dysfunction and improving both fibrosis and pathological changes in cardiac tissues of diabetic rats. These findings define for the first time that the effects of PIC against DCM can be attributed to its role in inflammation and oxidative stress inhibition.
•PIC inhibits cell apoptosis by reducing oxidative stress and inflammation.•The pic-mediated suppression of NF-κB activation is dependent on Nrf2.•PIC improves the cardiac function of DCM rats.•PIC suppresses diabetes-induced cardiac oxidative stress and inflammation.•PIC can be a promising and safe agent for the treatment of DCM.</description><subject>Cardiomyopathy</subject><subject>Diabetic</subject><subject>Inflammation</subject><subject>Nrf-2/HO-1</subject><subject>Oxidative stress</subject><subject>Piceatannol</subject><issn>0009-2797</issn><issn>1872-7786</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kMFu1DAURS1ERYfCB7BBXrLJ1HZiOxErqFqKVLVdwNp6sV9Uj5J4sD0D8wX9Jz6Cb8JDCktW1tU790o-hLzhbM0ZV-ebte39WjDeldxq2TwjK95qUWndqudkxRjrKqE7fUpeprQpkYmGvSCnNa9FLYRekcd7bxEyzHMYKYwj7j1kTNTPwwjTBNmHmcLsaPjhXUl7pClHTIkWkE7B7caFCQPND0hv4yDOr-8q_qd0e1X9-vmRbiE_fIfDcZU6Dz1mb6mF6HyYDuF4PbwiJwOMCV8_vWfk69Xll4vr6ubu0-eLDzeVrWWdq64bmobxlrUgnbQgsW1Q9Vr10HOhtB2kLdcOQTWqZ51qa6kE9sC4k82g6zPybtndxvBthymbySeL4wgzhl0yQijeKdnWTUH5gtoYUoo4mG30E8SD4cwc_ZuNKf7N0b9Z_JfO26f5XT-h-9f4K7wA7xcAyyf3HqNJ1uNs0fmINhsX_H_mfwP01JdX</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Li, Hao</creator><creator>Shi, Youyang</creator><creator>Wang, Xuliang</creator><creator>Li, Ping</creator><creator>Zhang, Songyue</creator><creator>Wu, Tingting</creator><creator>Yan, Yaoyao</creator><creator>Zhan, Yi</creator><creator>Ren, Yue</creator><creator>Rong, Xing</creator><creator>Xia, Tianhe</creator><creator>Chu, Maoping</creator><creator>Wu, Rongzhou</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20190901</creationdate><title>Piceatannol alleviates inflammation and oxidative stress via modulation of the Nrf2/HO-1 and NF-κB pathways in diabetic cardiomyopathy</title><author>Li, Hao ; Shi, Youyang ; Wang, Xuliang ; Li, Ping ; Zhang, Songyue ; Wu, Tingting ; Yan, Yaoyao ; Zhan, Yi ; Ren, Yue ; Rong, Xing ; Xia, Tianhe ; Chu, Maoping ; Wu, Rongzhou</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-99f4401808a5d5ca5e84e6b76bab1267cf5c1809ea646b09683562eba01d54f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Cardiomyopathy</topic><topic>Diabetic</topic><topic>Inflammation</topic><topic>Nrf-2/HO-1</topic><topic>Oxidative stress</topic><topic>Piceatannol</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Hao</creatorcontrib><creatorcontrib>Shi, Youyang</creatorcontrib><creatorcontrib>Wang, Xuliang</creatorcontrib><creatorcontrib>Li, Ping</creatorcontrib><creatorcontrib>Zhang, Songyue</creatorcontrib><creatorcontrib>Wu, Tingting</creatorcontrib><creatorcontrib>Yan, Yaoyao</creatorcontrib><creatorcontrib>Zhan, Yi</creatorcontrib><creatorcontrib>Ren, Yue</creatorcontrib><creatorcontrib>Rong, Xing</creatorcontrib><creatorcontrib>Xia, Tianhe</creatorcontrib><creatorcontrib>Chu, Maoping</creatorcontrib><creatorcontrib>Wu, Rongzhou</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chemico-biological interactions</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Hao</au><au>Shi, Youyang</au><au>Wang, Xuliang</au><au>Li, Ping</au><au>Zhang, Songyue</au><au>Wu, Tingting</au><au>Yan, Yaoyao</au><au>Zhan, Yi</au><au>Ren, Yue</au><au>Rong, Xing</au><au>Xia, Tianhe</au><au>Chu, Maoping</au><au>Wu, Rongzhou</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Piceatannol alleviates inflammation and oxidative stress via modulation of the Nrf2/HO-1 and NF-κB pathways in diabetic cardiomyopathy</atitle><jtitle>Chemico-biological interactions</jtitle><addtitle>Chem Biol Interact</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>310</volume><spage>108754</spage><epage>108754</epage><pages>108754-108754</pages><artnum>108754</artnum><issn>0009-2797</issn><eissn>1872-7786</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Diabetic cardiomyopathy (DCM) is one of the leading causes of morbidity and mortality in diabetic patients. Piceatannol (PIC) has protective effects against cardiovascular disease; however, it remains unknown whether it also protects against DCM. A Cell Counting Kit-8 (CCK-8) assay was used to evaluate the effects of PIC on the viability of high glucose (HG)-induced H9C2 cells. Protein expression and mRNA levels were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. In vivo, physical and biochemical analyses, together with transthoracic echocardiography and hemodynamic measurements, were used to detect the effects of PIC treatment on cardiac function in DCM rats. Reactive oxygen species production was determined using an ELISA kit, and inflammatory cytokines were detected by RT-PCR. Pathological changes were assessed by hematoxylin-eosin staining, immunohistochemical staining, and TUNEL staining. According to the results, PIC treatment improved cell viability and inhibited cell apoptosis in HG-induced H9C2 cardiac myoblasts. In addition, PIC not only attenuated the over-production of interleukin-6 (IL-6) (P < 0.05) and tumor necrosis factor alpha (TNF-α) (P < 0.05), but also improved the expression of nuclear factor E2-related factor 2 (Nrf2) (P < 0.05) and heme oxygenase-1 (HO-1) (P < 0.01). Importantly, knockdown of Nrf2 suppressed PIC-mediated activation of the Nrf2/HO-1 pathway and abolished its anti-inflammatory effects. In vivo, oral administration of PIC suppressed STZ-induced inflammation, oxidative stress hypertrophy, fibrosis(myocardial collagen volume fraction in 5 mg/kg and 10 mg/kg PIC group was decreased 25.83% and 55.61% compared with the DM group), and apoptosis(Caspase-3 level in 5 mg/kg and 10 mg/kg PIC group was decreased 13.21% and 33.91% compared with the DM group), thereby relieving cardiac dysfunction and improving both fibrosis and pathological changes in cardiac tissues of diabetic rats. These findings define for the first time that the effects of PIC against DCM can be attributed to its role in inflammation and oxidative stress inhibition.
•PIC inhibits cell apoptosis by reducing oxidative stress and inflammation.•The pic-mediated suppression of NF-κB activation is dependent on Nrf2.•PIC improves the cardiac function of DCM rats.•PIC suppresses diabetes-induced cardiac oxidative stress and inflammation.•PIC can be a promising and safe agent for the treatment of DCM.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>31323227</pmid><doi>10.1016/j.cbi.2019.108754</doi><tpages>1</tpages></addata></record> |
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subjects | Cardiomyopathy Diabetic Inflammation Nrf-2/HO-1 Oxidative stress Piceatannol |
title | Piceatannol alleviates inflammation and oxidative stress via modulation of the Nrf2/HO-1 and NF-κB pathways in diabetic cardiomyopathy |
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