Astragalus polysaccharide ameliorates vascular endothelial dysfunction by stimulating macrophage M2 polarization via potentiating Nrf2/HO-1 signaling pathway
•Macrophage polarization is a critical and initiating factor in atherosclerosis and related cardiovascular diseases in T2DM.•Astragalus polysaccharide potentiated anti-inflammatory responses by regulating macrophage subtype.•Activation of Nrf2/HO-1 by Astragalus polysaccharide alleviate macrophage a...
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| Veröffentlicht in: | Phytomedicine (Stuttgart) 2023-04, Vol.112, p.154667-154667, Article 154667 |
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| creator | Sha, Wenjun Zhao, Bei Wei, Huizhen Yang, Yunyi Yin, Hongping Gao, Jie Zhao, Weiwei Kong, Wenwen Ge, Guangbo Lei, Tao |
| description | •Macrophage polarization is a critical and initiating factor in atherosclerosis and related cardiovascular diseases in T2DM.•Astragalus polysaccharide potentiated anti-inflammatory responses by regulating macrophage subtype.•Activation of Nrf2/HO-1 by Astragalus polysaccharide alleviate macrophage and high glucose-induced endothelial dysfunction.
Oxidative stress and chronic non-infectious inflammation caused vascular endothelial dysfunction (VED) is a critical and initiating factor in Type 2 diabetes induced vascular complications, while macrophage polarization plays a regulatory role in VED. Astragalus polysaccharide (APS) has been widely used for treating diabetic vascular diseases, but its mechanisms of action have not been fully elucidated.
This study aimed to investigate the modulatory effects of APS on macrophage polarization and to reveal the potential mechanisms of APS in LPS and HG stimulated macrophages and diabetic model rats.
In vitro and in vivo studies were used to explore the mechanism of APS. The macrophage polarization and reactive oxygen species (ROS) release was monitored by flow cytometry and the associated inflammatory factors were detected by ELISA. For oxidative stress regulatory pathway detection, protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) was measured by Western blotting. The vascular endothelial functions were measured by transwell, tube formation assay, scratch assay, adhesion assay. The thoracic aorta pathological changes were evaluated by Haematoxylin-eosin and immunohistochemistry.
In vitro, APS inhibited the LPS/HG-stimulated THP-1 macrophage differentiated into macrophage M1, coupling with reduction in the ROS production and pro-inflammatory factors (TNF-α, IL-6, IL-12) release. Furthermore, endothelial cells proliferation and apoptosis were ameliorated after APS treatment. Meanwhile, APS-treated THP-1/macrophage occurred a differentiation into M2 polarization and anti-inflammatory factors (IL-4, IL-10, and Arg-1) release via enhancing Nrf2/HO-1 signaling pathway, which could be disturbed by using siNrf2. APS promoted the migration and angiogenesis of endothelial cells in co-cultured of HUVECs and macrophages under high glucose. Finally, similar results were observed in vivo, APS alleviated thoracic aorta complications of diabetic rats accompanied by a remarkable reduction in inflammation and an increased in the number of anti-inflammatory macrophage polarization.
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| doi_str_mv | 10.1016/j.phymed.2023.154667 |
| format | Article |
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Oxidative stress and chronic non-infectious inflammation caused vascular endothelial dysfunction (VED) is a critical and initiating factor in Type 2 diabetes induced vascular complications, while macrophage polarization plays a regulatory role in VED. Astragalus polysaccharide (APS) has been widely used for treating diabetic vascular diseases, but its mechanisms of action have not been fully elucidated.
This study aimed to investigate the modulatory effects of APS on macrophage polarization and to reveal the potential mechanisms of APS in LPS and HG stimulated macrophages and diabetic model rats.
In vitro and in vivo studies were used to explore the mechanism of APS. The macrophage polarization and reactive oxygen species (ROS) release was monitored by flow cytometry and the associated inflammatory factors were detected by ELISA. For oxidative stress regulatory pathway detection, protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) was measured by Western blotting. The vascular endothelial functions were measured by transwell, tube formation assay, scratch assay, adhesion assay. The thoracic aorta pathological changes were evaluated by Haematoxylin-eosin and immunohistochemistry.
In vitro, APS inhibited the LPS/HG-stimulated THP-1 macrophage differentiated into macrophage M1, coupling with reduction in the ROS production and pro-inflammatory factors (TNF-α, IL-6, IL-12) release. Furthermore, endothelial cells proliferation and apoptosis were ameliorated after APS treatment. Meanwhile, APS-treated THP-1/macrophage occurred a differentiation into M2 polarization and anti-inflammatory factors (IL-4, IL-10, and Arg-1) release via enhancing Nrf2/HO-1 signaling pathway, which could be disturbed by using siNrf2. APS promoted the migration and angiogenesis of endothelial cells in co-cultured of HUVECs and macrophages under high glucose. Finally, similar results were observed in vivo, APS alleviated thoracic aorta complications of diabetic rats accompanied by a remarkable reduction in inflammation and an increased in the number of anti-inflammatory macrophage polarization.
Our results demonstrated that APS ameliorated vascular endothelial dysfunction in diabetes by stimulating macrophage polarization to M2 via enhancing the Nrf2/HO-1 pathway.</description><identifier>ISSN: 0944-7113</identifier><identifier>EISSN: 1618-095X</identifier><identifier>DOI: 10.1016/j.phymed.2023.154667</identifier><identifier>PMID: 36842218</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Animals ; Anti-Inflammatory Agents - pharmacology ; Astragalus Plant ; Astragalus polysaccharide (APS) ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes vascular complications ; Endothelial Cells - metabolism ; Heme Oxygenase-1 - metabolism ; Inflammation - metabolism ; Lipopolysaccharides - pharmacology ; Macrophage polarization ; Macrophages - metabolism ; NF-E2-Related Factor 2 - metabolism ; Nrf2/HO-1 signaling pathway ; Polysaccharides - pharmacology ; Rats ; Reactive Oxygen Species - metabolism ; Signal Transduction ; Vascular endothelial dysfunction</subject><ispartof>Phytomedicine (Stuttgart), 2023-04, Vol.112, p.154667-154667, Article 154667</ispartof><rights>2023</rights><rights>Copyright © 2023. Published by Elsevier GmbH.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-5cecd78afe4128be3d08b8f9f7f3ee862178590f9edb95c1460118b0da39de213</citedby><cites>FETCH-LOGICAL-c362t-5cecd78afe4128be3d08b8f9f7f3ee862178590f9edb95c1460118b0da39de213</cites><orcidid>0000-0001-5474-4476 ; 0000-0002-0756-0006</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.phymed.2023.154667$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36842218$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sha, Wenjun</creatorcontrib><creatorcontrib>Zhao, Bei</creatorcontrib><creatorcontrib>Wei, Huizhen</creatorcontrib><creatorcontrib>Yang, Yunyi</creatorcontrib><creatorcontrib>Yin, Hongping</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>Zhao, Weiwei</creatorcontrib><creatorcontrib>Kong, Wenwen</creatorcontrib><creatorcontrib>Ge, Guangbo</creatorcontrib><creatorcontrib>Lei, Tao</creatorcontrib><title>Astragalus polysaccharide ameliorates vascular endothelial dysfunction by stimulating macrophage M2 polarization via potentiating Nrf2/HO-1 signaling pathway</title><title>Phytomedicine (Stuttgart)</title><addtitle>Phytomedicine</addtitle><description>•Macrophage polarization is a critical and initiating factor in atherosclerosis and related cardiovascular diseases in T2DM.•Astragalus polysaccharide potentiated anti-inflammatory responses by regulating macrophage subtype.•Activation of Nrf2/HO-1 by Astragalus polysaccharide alleviate macrophage and high glucose-induced endothelial dysfunction.
Oxidative stress and chronic non-infectious inflammation caused vascular endothelial dysfunction (VED) is a critical and initiating factor in Type 2 diabetes induced vascular complications, while macrophage polarization plays a regulatory role in VED. Astragalus polysaccharide (APS) has been widely used for treating diabetic vascular diseases, but its mechanisms of action have not been fully elucidated.
This study aimed to investigate the modulatory effects of APS on macrophage polarization and to reveal the potential mechanisms of APS in LPS and HG stimulated macrophages and diabetic model rats.
In vitro and in vivo studies were used to explore the mechanism of APS. The macrophage polarization and reactive oxygen species (ROS) release was monitored by flow cytometry and the associated inflammatory factors were detected by ELISA. For oxidative stress regulatory pathway detection, protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) was measured by Western blotting. The vascular endothelial functions were measured by transwell, tube formation assay, scratch assay, adhesion assay. The thoracic aorta pathological changes were evaluated by Haematoxylin-eosin and immunohistochemistry.
In vitro, APS inhibited the LPS/HG-stimulated THP-1 macrophage differentiated into macrophage M1, coupling with reduction in the ROS production and pro-inflammatory factors (TNF-α, IL-6, IL-12) release. Furthermore, endothelial cells proliferation and apoptosis were ameliorated after APS treatment. Meanwhile, APS-treated THP-1/macrophage occurred a differentiation into M2 polarization and anti-inflammatory factors (IL-4, IL-10, and Arg-1) release via enhancing Nrf2/HO-1 signaling pathway, which could be disturbed by using siNrf2. APS promoted the migration and angiogenesis of endothelial cells in co-cultured of HUVECs and macrophages under high glucose. Finally, similar results were observed in vivo, APS alleviated thoracic aorta complications of diabetic rats accompanied by a remarkable reduction in inflammation and an increased in the number of anti-inflammatory macrophage polarization.
Our results demonstrated that APS ameliorated vascular endothelial dysfunction in diabetes by stimulating macrophage polarization to M2 via enhancing the Nrf2/HO-1 pathway.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Astragalus Plant</subject><subject>Astragalus polysaccharide (APS)</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes vascular complications</subject><subject>Endothelial Cells - metabolism</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Inflammation - metabolism</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Macrophage polarization</subject><subject>Macrophages - metabolism</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Nrf2/HO-1 signaling pathway</subject><subject>Polysaccharides - pharmacology</subject><subject>Rats</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Signal Transduction</subject><subject>Vascular endothelial dysfunction</subject><issn>0944-7113</issn><issn>1618-095X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1TAQhi1ERQ-FN0DISzY5tR0ncTZIVVUoUi-bIrGzJvbkxEe5YTsHhXfhXUlIu2U10sw3_2j0EfKBsz1nPL887sdm7tDuBRPpnmcyz4tXZMdzrhJWZj9ekx0rpUwKztNz8jaEI2NclgV7Q87TXEkhuNqRP1chejhAOwU6Du0cwJgGvLNIocPWDR4iBnqCYKYWPMXeDrFZBtBSO4d66k10Q0-rmYbouoWJrj_QDowfxgYOSO_FGrxE_oZ_5MnB0ojYR7exD74Wl7ePCafBHXpo194IsfkF8ztyVkMb8P1zvSDfv9w8Xd8md49fv11f3SUmzUVMMoPGFgpqlFyoClPLVKXqsi7qFFHlghcqK1ldoq3KzHCZM85VxSykpUXB0wvyacsd_fBzwhB154LBtoUehyloUSgmlWKFXFC5ocuDIXis9ehdB37WnOlVjD7qTYxexehNzLL28fnCVK2zl6UXEwvweQNw-fPk0OtgHPYGrfNooraD-_-Fv1c0pdU</recordid><startdate>202304</startdate><enddate>202304</enddate><creator>Sha, Wenjun</creator><creator>Zhao, Bei</creator><creator>Wei, Huizhen</creator><creator>Yang, Yunyi</creator><creator>Yin, Hongping</creator><creator>Gao, Jie</creator><creator>Zhao, Weiwei</creator><creator>Kong, Wenwen</creator><creator>Ge, Guangbo</creator><creator>Lei, Tao</creator><general>Elsevier GmbH</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><orcidid>https://orcid.org/0000-0001-5474-4476</orcidid><orcidid>https://orcid.org/0000-0002-0756-0006</orcidid></search><sort><creationdate>202304</creationdate><title>Astragalus polysaccharide ameliorates vascular endothelial dysfunction by stimulating macrophage M2 polarization via potentiating Nrf2/HO-1 signaling pathway</title><author>Sha, Wenjun ; Zhao, Bei ; Wei, Huizhen ; Yang, Yunyi ; Yin, Hongping ; Gao, Jie ; Zhao, Weiwei ; Kong, Wenwen ; Ge, Guangbo ; Lei, Tao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-5cecd78afe4128be3d08b8f9f7f3ee862178590f9edb95c1460118b0da39de213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Astragalus Plant</topic><topic>Astragalus polysaccharide (APS)</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes vascular complications</topic><topic>Endothelial Cells - metabolism</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Inflammation - metabolism</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Macrophage polarization</topic><topic>Macrophages - metabolism</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Nrf2/HO-1 signaling pathway</topic><topic>Polysaccharides - pharmacology</topic><topic>Rats</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Signal Transduction</topic><topic>Vascular endothelial dysfunction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sha, Wenjun</creatorcontrib><creatorcontrib>Zhao, Bei</creatorcontrib><creatorcontrib>Wei, Huizhen</creatorcontrib><creatorcontrib>Yang, Yunyi</creatorcontrib><creatorcontrib>Yin, Hongping</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>Zhao, Weiwei</creatorcontrib><creatorcontrib>Kong, Wenwen</creatorcontrib><creatorcontrib>Ge, Guangbo</creatorcontrib><creatorcontrib>Lei, Tao</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>Phytomedicine (Stuttgart)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sha, Wenjun</au><au>Zhao, Bei</au><au>Wei, Huizhen</au><au>Yang, Yunyi</au><au>Yin, Hongping</au><au>Gao, Jie</au><au>Zhao, Weiwei</au><au>Kong, Wenwen</au><au>Ge, Guangbo</au><au>Lei, Tao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Astragalus polysaccharide ameliorates vascular endothelial dysfunction by stimulating macrophage M2 polarization via potentiating Nrf2/HO-1 signaling pathway</atitle><jtitle>Phytomedicine (Stuttgart)</jtitle><addtitle>Phytomedicine</addtitle><date>2023-04</date><risdate>2023</risdate><volume>112</volume><spage>154667</spage><epage>154667</epage><pages>154667-154667</pages><artnum>154667</artnum><issn>0944-7113</issn><eissn>1618-095X</eissn><abstract>•Macrophage polarization is a critical and initiating factor in atherosclerosis and related cardiovascular diseases in T2DM.•Astragalus polysaccharide potentiated anti-inflammatory responses by regulating macrophage subtype.•Activation of Nrf2/HO-1 by Astragalus polysaccharide alleviate macrophage and high glucose-induced endothelial dysfunction.
Oxidative stress and chronic non-infectious inflammation caused vascular endothelial dysfunction (VED) is a critical and initiating factor in Type 2 diabetes induced vascular complications, while macrophage polarization plays a regulatory role in VED. Astragalus polysaccharide (APS) has been widely used for treating diabetic vascular diseases, but its mechanisms of action have not been fully elucidated.
This study aimed to investigate the modulatory effects of APS on macrophage polarization and to reveal the potential mechanisms of APS in LPS and HG stimulated macrophages and diabetic model rats.
In vitro and in vivo studies were used to explore the mechanism of APS. The macrophage polarization and reactive oxygen species (ROS) release was monitored by flow cytometry and the associated inflammatory factors were detected by ELISA. For oxidative stress regulatory pathway detection, protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) was measured by Western blotting. The vascular endothelial functions were measured by transwell, tube formation assay, scratch assay, adhesion assay. The thoracic aorta pathological changes were evaluated by Haematoxylin-eosin and immunohistochemistry.
In vitro, APS inhibited the LPS/HG-stimulated THP-1 macrophage differentiated into macrophage M1, coupling with reduction in the ROS production and pro-inflammatory factors (TNF-α, IL-6, IL-12) release. Furthermore, endothelial cells proliferation and apoptosis were ameliorated after APS treatment. Meanwhile, APS-treated THP-1/macrophage occurred a differentiation into M2 polarization and anti-inflammatory factors (IL-4, IL-10, and Arg-1) release via enhancing Nrf2/HO-1 signaling pathway, which could be disturbed by using siNrf2. APS promoted the migration and angiogenesis of endothelial cells in co-cultured of HUVECs and macrophages under high glucose. Finally, similar results were observed in vivo, APS alleviated thoracic aorta complications of diabetic rats accompanied by a remarkable reduction in inflammation and an increased in the number of anti-inflammatory macrophage polarization.
Our results demonstrated that APS ameliorated vascular endothelial dysfunction in diabetes by stimulating macrophage polarization to M2 via enhancing the Nrf2/HO-1 pathway.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>36842218</pmid><doi>10.1016/j.phymed.2023.154667</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-5474-4476</orcidid><orcidid>https://orcid.org/0000-0002-0756-0006</orcidid></addata></record> |
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| subjects | Animals Anti-Inflammatory Agents - pharmacology Astragalus Plant Astragalus polysaccharide (APS) Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Type 2 - metabolism Diabetes vascular complications Endothelial Cells - metabolism Heme Oxygenase-1 - metabolism Inflammation - metabolism Lipopolysaccharides - pharmacology Macrophage polarization Macrophages - metabolism NF-E2-Related Factor 2 - metabolism Nrf2/HO-1 signaling pathway Polysaccharides - pharmacology Rats Reactive Oxygen Species - metabolism Signal Transduction Vascular endothelial dysfunction |
| title | Astragalus polysaccharide ameliorates vascular endothelial dysfunction by stimulating macrophage M2 polarization via potentiating Nrf2/HO-1 signaling pathway |
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