Salvianolic Acid A Protects Against Diabetic Nephropathy through Ameliorating Glomerular Endothelial Dysfunction via Inhibiting AGE-RAGE Signaling
Background/Aims: Glomerular endothelium dysfunction leads to the progression of renal architectonic and functional abnormalities in early-stage diabetic nephropathy (DN). Advanced glycation end products (AGEs) and receptor for AGEs (RAGE) are proved to play important roles in diabetic nephropathy. T...
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| Veröffentlicht in: | Cellular physiology and biochemistry 2017-01, Vol.44 (6), p.2378-2394 |
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| creator | Hou, Biyu Qiang, Guifen Zhao, Yuerong Yang, Xiuying Chen, Xi Yan, Yu Wang, Xiaobo Liu, Chenge Zhang, Li Du, Guanhua |
| description | Background/Aims: Glomerular endothelium dysfunction leads to the progression of renal architectonic and functional abnormalities in early-stage diabetic nephropathy (DN). Advanced glycation end products (AGEs) and receptor for AGEs (RAGE) are proved to play important roles in diabetic nephropathy. This study investigated the role of Salvianolic acid A (SalA) on early-stage DN and its possible underlying mechanism. Methods: In vitro AGEs formation and breaking rate were measured to illustrate the effect of SalA on AGEs. Type 2 diabetic nephropathy rats were induced by high-fat diet and low-dose streptozocin (STZ). After eight-week treatment with SalA 1 mg/kg/day, 24h-urine protein, creatinine clearance was tested and renal structural injury was assessed by PAS and PASM staining. Primary glomerular endothelial cell permeability was evaluated after exposed to AGEs. AGEs-induced RhoA/ROCK and subsequently activated disarrange of cytoskeleton were assessed by western blot and immunofluorescence. Results: Biochemical assay and histological examination demonstrated that SalA markedly reduced endothelium loss and glomerular hyperfiltration, suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced urinary albumin and ameliorated renal function. Further investigation suggested that SalA exerted its renoprotective effects through inhibiting AGE-RAGE signaling. It not only inhibited formation of AGEs and increased its breaking in vitro, but also reduced AGEs accumulation in vivo and downregulated RAGE expression. SalA restored glomerular endothelial permeability through suppressing AGEs-induced rearrangement of actin cytoskeleton via AGE-RAGE-RhoA/ ROCK pathway. Moreover, SalA attenuated oxidative stress induced by AGEs, subsequently alleviated inflammation and restored the disturbed autophagy in glomerular endothelial cell and diabetic rats via AGE-RAGE-Nox4 axis. Conclusion: Our study indicated that SalA restored glomerular endothelial function and alleviated renal structural deterioration through inhibiting AGE-RAGE, thus effectively ameliorated early-stage diabetic nephropathy. SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy. |
| doi_str_mv | 10.1159/000486154 |
| format | Article |
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Advanced glycation end products (AGEs) and receptor for AGEs (RAGE) are proved to play important roles in diabetic nephropathy. This study investigated the role of Salvianolic acid A (SalA) on early-stage DN and its possible underlying mechanism. Methods: In vitro AGEs formation and breaking rate were measured to illustrate the effect of SalA on AGEs. Type 2 diabetic nephropathy rats were induced by high-fat diet and low-dose streptozocin (STZ). After eight-week treatment with SalA 1 mg/kg/day, 24h-urine protein, creatinine clearance was tested and renal structural injury was assessed by PAS and PASM staining. Primary glomerular endothelial cell permeability was evaluated after exposed to AGEs. AGEs-induced RhoA/ROCK and subsequently activated disarrange of cytoskeleton were assessed by western blot and immunofluorescence. Results: Biochemical assay and histological examination demonstrated that SalA markedly reduced endothelium loss and glomerular hyperfiltration, suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced urinary albumin and ameliorated renal function. Further investigation suggested that SalA exerted its renoprotective effects through inhibiting AGE-RAGE signaling. It not only inhibited formation of AGEs and increased its breaking in vitro, but also reduced AGEs accumulation in vivo and downregulated RAGE expression. SalA restored glomerular endothelial permeability through suppressing AGEs-induced rearrangement of actin cytoskeleton via AGE-RAGE-RhoA/ ROCK pathway. Moreover, SalA attenuated oxidative stress induced by AGEs, subsequently alleviated inflammation and restored the disturbed autophagy in glomerular endothelial cell and diabetic rats via AGE-RAGE-Nox4 axis. Conclusion: Our study indicated that SalA restored glomerular endothelial function and alleviated renal structural deterioration through inhibiting AGE-RAGE, thus effectively ameliorated early-stage diabetic nephropathy. SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.</description><identifier>ISSN: 1015-8987</identifier><identifier>EISSN: 1421-9778</identifier><identifier>DOI: 10.1159/000486154</identifier><identifier>PMID: 29262395</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Acids ; Advanced glycation end products ; Age ; Animals ; Autophagy ; Caffeic Acids - therapeutic use ; Cell adhesion & migration ; Cells, Cultured ; Cytokines ; Diabetes ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - physiopathology ; Diabetic Nephropathies - etiology ; Diabetic Nephropathies - metabolism ; Diabetic Nephropathies - physiopathology ; Diabetic Nephropathies - prevention & control ; Diabetic nephropathy ; Diabetic retinopathy ; Drugs, Chinese Herbal - therapeutic use ; Endothelium - drug effects ; Endothelium - metabolism ; Endothelium - physiopathology ; Glomerular endothelia dysfunction ; Glucose ; Glycation End Products, Advanced - metabolism ; Inflammation ; Kidney Glomerulus - drug effects ; Kidney Glomerulus - metabolism ; Kidney Glomerulus - physiopathology ; Kinases ; Laboratory animals ; Lactates - therapeutic use ; Male ; Original Paper ; Oxidative stress ; Oxidative Stress - drug effects ; Permeability ; Protective Agents - therapeutic use ; Proteins ; Rats, Sprague-Dawley ; Receptor for Advanced Glycation End Products - metabolism ; Rodents ; Salvianolic acid A ; Signal Transduction - drug effects ; Tumor necrosis factor-TNF</subject><ispartof>Cellular physiology and biochemistry, 2017-01, Vol.44 (6), p.2378-2394</ispartof><rights>2017 The Author(s). Published by S. Karger AG, Basel</rights><rights>2017 The Author(s). Published by S. Karger AG, Basel.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-b2e58d065ababf82870945e2dd196525682a5aed284ef534d5e79b280d3788883</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,2096,27612,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29262395$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hou, Biyu</creatorcontrib><creatorcontrib>Qiang, Guifen</creatorcontrib><creatorcontrib>Zhao, Yuerong</creatorcontrib><creatorcontrib>Yang, Xiuying</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Yan, Yu</creatorcontrib><creatorcontrib>Wang, Xiaobo</creatorcontrib><creatorcontrib>Liu, Chenge</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Du, Guanhua</creatorcontrib><title>Salvianolic Acid A Protects Against Diabetic Nephropathy through Ameliorating Glomerular Endothelial Dysfunction via Inhibiting AGE-RAGE Signaling</title><title>Cellular physiology and biochemistry</title><addtitle>Cell Physiol Biochem</addtitle><description>Background/Aims: Glomerular endothelium dysfunction leads to the progression of renal architectonic and functional abnormalities in early-stage diabetic nephropathy (DN). Advanced glycation end products (AGEs) and receptor for AGEs (RAGE) are proved to play important roles in diabetic nephropathy. This study investigated the role of Salvianolic acid A (SalA) on early-stage DN and its possible underlying mechanism. Methods: In vitro AGEs formation and breaking rate were measured to illustrate the effect of SalA on AGEs. Type 2 diabetic nephropathy rats were induced by high-fat diet and low-dose streptozocin (STZ). After eight-week treatment with SalA 1 mg/kg/day, 24h-urine protein, creatinine clearance was tested and renal structural injury was assessed by PAS and PASM staining. Primary glomerular endothelial cell permeability was evaluated after exposed to AGEs. AGEs-induced RhoA/ROCK and subsequently activated disarrange of cytoskeleton were assessed by western blot and immunofluorescence. Results: Biochemical assay and histological examination demonstrated that SalA markedly reduced endothelium loss and glomerular hyperfiltration, suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced urinary albumin and ameliorated renal function. Further investigation suggested that SalA exerted its renoprotective effects through inhibiting AGE-RAGE signaling. It not only inhibited formation of AGEs and increased its breaking in vitro, but also reduced AGEs accumulation in vivo and downregulated RAGE expression. SalA restored glomerular endothelial permeability through suppressing AGEs-induced rearrangement of actin cytoskeleton via AGE-RAGE-RhoA/ ROCK pathway. Moreover, SalA attenuated oxidative stress induced by AGEs, subsequently alleviated inflammation and restored the disturbed autophagy in glomerular endothelial cell and diabetic rats via AGE-RAGE-Nox4 axis. Conclusion: Our study indicated that SalA restored glomerular endothelial function and alleviated renal structural deterioration through inhibiting AGE-RAGE, thus effectively ameliorated early-stage diabetic nephropathy. SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.</description><subject>Acids</subject><subject>Advanced glycation end products</subject><subject>Age</subject><subject>Animals</subject><subject>Autophagy</subject><subject>Caffeic Acids - therapeutic use</subject><subject>Cell adhesion & migration</subject><subject>Cells, Cultured</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Diabetic Nephropathies - etiology</subject><subject>Diabetic Nephropathies - metabolism</subject><subject>Diabetic Nephropathies - physiopathology</subject><subject>Diabetic Nephropathies - prevention & control</subject><subject>Diabetic nephropathy</subject><subject>Diabetic retinopathy</subject><subject>Drugs, Chinese Herbal - therapeutic use</subject><subject>Endothelium - drug effects</subject><subject>Endothelium - metabolism</subject><subject>Endothelium - physiopathology</subject><subject>Glomerular endothelia dysfunction</subject><subject>Glucose</subject><subject>Glycation End Products, Advanced - metabolism</subject><subject>Inflammation</subject><subject>Kidney Glomerulus - drug effects</subject><subject>Kidney Glomerulus - metabolism</subject><subject>Kidney Glomerulus - physiopathology</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Lactates - therapeutic use</subject><subject>Male</subject><subject>Original Paper</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Permeability</subject><subject>Protective Agents - therapeutic use</subject><subject>Proteins</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor for Advanced Glycation End Products - metabolism</subject><subject>Rodents</subject><subject>Salvianolic acid A</subject><subject>Signal Transduction - drug effects</subject><subject>Tumor necrosis factor-TNF</subject><issn>1015-8987</issn><issn>1421-9778</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptkUGP1CAUxxujcdfVg3djSLzooQoMFDjW2XGcZKMbV8-EFtoyMqUCNZmvsZ942Z1xTIwc4PH4vf_j5V8ULxF8jxAVHyCEhFeIkkfFOSIYlYIx_jjHENGSC87OimcxbmG-MoGfFmdY4AovBD0vbm-U-23V6J1tQd1aDWpwHXwybYqg7pUdYwKXVjUmZeCLmYbgJ5WGPUg5mvsB1DvjrA8q2bEHa-d3JsxOBbAatU9DflMOXO5jN49tsn4EuRvYjINt7ENFvV6V3_IGbmw_KpdTz4snnXLRvDieF8WPT6vvy8_l1df1ZllflS2lLJUNNpRrWFHVqKbjmDMoCDVYayQqimnFsaLKaMyJ6eiCaGqYaDCHesF4XouLYnPQ1V5t5RTsToW99MrKh4QPvVQhT-2MFALDhqMWcWMI7rRodNtiwTTSrOoIzlpvD1pT8L9mE5Pc2dga59Ro_BwlEkwQwbiAGX3zD7r1c8ijR4kRYohkZ-4F3x2oNvgYg-lOH0RQ3psuT6Zn9vVRcW52Rp_IPy7_bflThd6EE7C8_niQkJPuMvXqv9Sxyx0nzLu4</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Hou, Biyu</creator><creator>Qiang, Guifen</creator><creator>Zhao, Yuerong</creator><creator>Yang, Xiuying</creator><creator>Chen, Xi</creator><creator>Yan, Yu</creator><creator>Wang, Xiaobo</creator><creator>Liu, Chenge</creator><creator>Zhang, Li</creator><creator>Du, Guanhua</creator><general>S. Karger AG</general><general>Cell Physiol Biochem Press GmbH & Co KG</general><scope>M--</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>DOA</scope></search><sort><creationdate>20170101</creationdate><title>Salvianolic Acid A Protects Against Diabetic Nephropathy through Ameliorating Glomerular Endothelial Dysfunction via Inhibiting AGE-RAGE Signaling</title><author>Hou, Biyu ; Qiang, Guifen ; Zhao, Yuerong ; Yang, Xiuying ; Chen, Xi ; Yan, Yu ; Wang, Xiaobo ; Liu, Chenge ; Zhang, Li ; Du, Guanhua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-b2e58d065ababf82870945e2dd196525682a5aed284ef534d5e79b280d3788883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acids</topic><topic>Advanced glycation end products</topic><topic>Age</topic><topic>Animals</topic><topic>Autophagy</topic><topic>Caffeic Acids - therapeutic use</topic><topic>Cell adhesion & migration</topic><topic>Cells, Cultured</topic><topic>Cytokines</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Diabetic Nephropathies - etiology</topic><topic>Diabetic Nephropathies - metabolism</topic><topic>Diabetic Nephropathies - physiopathology</topic><topic>Diabetic Nephropathies - prevention & control</topic><topic>Diabetic nephropathy</topic><topic>Diabetic retinopathy</topic><topic>Drugs, Chinese Herbal - therapeutic use</topic><topic>Endothelium - drug effects</topic><topic>Endothelium - metabolism</topic><topic>Endothelium - physiopathology</topic><topic>Glomerular endothelia dysfunction</topic><topic>Glucose</topic><topic>Glycation End Products, Advanced - metabolism</topic><topic>Inflammation</topic><topic>Kidney Glomerulus - drug effects</topic><topic>Kidney Glomerulus - metabolism</topic><topic>Kidney Glomerulus - physiopathology</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Lactates - therapeutic use</topic><topic>Male</topic><topic>Original Paper</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Permeability</topic><topic>Protective Agents - therapeutic use</topic><topic>Proteins</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor for Advanced Glycation End Products - metabolism</topic><topic>Rodents</topic><topic>Salvianolic acid A</topic><topic>Signal Transduction - drug effects</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hou, Biyu</creatorcontrib><creatorcontrib>Qiang, Guifen</creatorcontrib><creatorcontrib>Zhao, Yuerong</creatorcontrib><creatorcontrib>Yang, Xiuying</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Yan, Yu</creatorcontrib><creatorcontrib>Wang, Xiaobo</creatorcontrib><creatorcontrib>Liu, Chenge</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Du, Guanhua</creatorcontrib><collection>Karger Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Cellular physiology and biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hou, Biyu</au><au>Qiang, Guifen</au><au>Zhao, Yuerong</au><au>Yang, Xiuying</au><au>Chen, Xi</au><au>Yan, Yu</au><au>Wang, Xiaobo</au><au>Liu, Chenge</au><au>Zhang, Li</au><au>Du, Guanhua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Salvianolic Acid A Protects Against Diabetic Nephropathy through Ameliorating Glomerular Endothelial Dysfunction via Inhibiting AGE-RAGE Signaling</atitle><jtitle>Cellular physiology and biochemistry</jtitle><addtitle>Cell Physiol Biochem</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>44</volume><issue>6</issue><spage>2378</spage><epage>2394</epage><pages>2378-2394</pages><issn>1015-8987</issn><eissn>1421-9778</eissn><abstract>Background/Aims: Glomerular endothelium dysfunction leads to the progression of renal architectonic and functional abnormalities in early-stage diabetic nephropathy (DN). Advanced glycation end products (AGEs) and receptor for AGEs (RAGE) are proved to play important roles in diabetic nephropathy. This study investigated the role of Salvianolic acid A (SalA) on early-stage DN and its possible underlying mechanism. Methods: In vitro AGEs formation and breaking rate were measured to illustrate the effect of SalA on AGEs. Type 2 diabetic nephropathy rats were induced by high-fat diet and low-dose streptozocin (STZ). After eight-week treatment with SalA 1 mg/kg/day, 24h-urine protein, creatinine clearance was tested and renal structural injury was assessed by PAS and PASM staining. Primary glomerular endothelial cell permeability was evaluated after exposed to AGEs. AGEs-induced RhoA/ROCK and subsequently activated disarrange of cytoskeleton were assessed by western blot and immunofluorescence. Results: Biochemical assay and histological examination demonstrated that SalA markedly reduced endothelium loss and glomerular hyperfiltration, suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced urinary albumin and ameliorated renal function. Further investigation suggested that SalA exerted its renoprotective effects through inhibiting AGE-RAGE signaling. It not only inhibited formation of AGEs and increased its breaking in vitro, but also reduced AGEs accumulation in vivo and downregulated RAGE expression. SalA restored glomerular endothelial permeability through suppressing AGEs-induced rearrangement of actin cytoskeleton via AGE-RAGE-RhoA/ ROCK pathway. Moreover, SalA attenuated oxidative stress induced by AGEs, subsequently alleviated inflammation and restored the disturbed autophagy in glomerular endothelial cell and diabetic rats via AGE-RAGE-Nox4 axis. Conclusion: Our study indicated that SalA restored glomerular endothelial function and alleviated renal structural deterioration through inhibiting AGE-RAGE, thus effectively ameliorated early-stage diabetic nephropathy. SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>29262395</pmid><doi>10.1159/000486154</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acids Advanced glycation end products Age Animals Autophagy Caffeic Acids - therapeutic use Cell adhesion & migration Cells, Cultured Cytokines Diabetes Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - physiopathology Diabetic Nephropathies - etiology Diabetic Nephropathies - metabolism Diabetic Nephropathies - physiopathology Diabetic Nephropathies - prevention & control Diabetic nephropathy Diabetic retinopathy Drugs, Chinese Herbal - therapeutic use Endothelium - drug effects Endothelium - metabolism Endothelium - physiopathology Glomerular endothelia dysfunction Glucose Glycation End Products, Advanced - metabolism Inflammation Kidney Glomerulus - drug effects Kidney Glomerulus - metabolism Kidney Glomerulus - physiopathology Kinases Laboratory animals Lactates - therapeutic use Male Original Paper Oxidative stress Oxidative Stress - drug effects Permeability Protective Agents - therapeutic use Proteins Rats, Sprague-Dawley Receptor for Advanced Glycation End Products - metabolism Rodents Salvianolic acid A Signal Transduction - drug effects Tumor necrosis factor-TNF |
| title | Salvianolic Acid A Protects Against Diabetic Nephropathy through Ameliorating Glomerular Endothelial Dysfunction via Inhibiting AGE-RAGE Signaling |
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