Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging‐Induced Renal Inflammation and Senescence via NADPH Oxidase‐Mediated Reactive Oxygen Generation

The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age‐related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2‐ or 8‐mg/kg body weight...

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Veröffentlicht in:Phytotherapy research 2017-05, Vol.31 (5), p.721-728
Hauptverfasser: Park, Chan Hum, Shin, Sung Ho, Lee, Eun Kyeong, Kim, Dae Hyun, Kim, Min‐Jo, Roh, Seong‐Soo, Yokozawa, Takako, Chung, Hae Young
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container_issue 5
container_start_page 721
container_title Phytotherapy research
container_volume 31
creator Park, Chan Hum
Shin, Sung Ho
Lee, Eun Kyeong
Kim, Dae Hyun
Kim, Min‐Jo
Roh, Seong‐Soo
Yokozawa, Takako
Chung, Hae Young
description The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age‐related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2‐ or 8‐mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22phox), phospho‐p38, nuclear factor‐kappa B p65, cyclooxygenase‐2, and inducible nitric oxide synthase. In addition, MLB‐treated old rats showed lower levels of senescence‐related proteins such as p16, ADP‐ribosylation factor 6, p53, and p21 through effects on the mitogen‐activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age‐related increase in serum urea nitrogen, reflecting renal dysfunction, up‐regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley & Sons, Ltd.
doi_str_mv 10.1002/ptr.5789
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Magnesium lithospermate B was orally administered at a dose of 2‐ or 8‐mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22phox), phospho‐p38, nuclear factor‐kappa B p65, cyclooxygenase‐2, and inducible nitric oxide synthase. In addition, MLB‐treated old rats showed lower levels of senescence‐related proteins such as p16, ADP‐ribosylation factor 6, p53, and p21 through effects on the mitogen‐activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age‐related increase in serum urea nitrogen, reflecting renal dysfunction, up‐regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley &amp; Sons, Ltd.</description><identifier>ISSN: 0951-418X</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.5789</identifier><identifier>PMID: 28211114</identifier><identifier>CODEN: PHYREH</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adenosine diphosphate ; ADP-ribosylation ; ADP-ribosylation factor 6 ; ADP-Ribosylation Factors ; Aging ; Aging (artificial) ; Aging - drug effects ; Aging - physiology ; Animals ; Body weight ; Cyclooxygenase 2 - metabolism ; Cyclooxygenase-2 ; Drugs, Chinese Herbal - chemistry ; Drugs, Chinese Herbal - pharmacology ; Fuel consumption ; GTP-binding protein ; inflammation ; Inflammation - metabolism ; Injury prevention ; Kidney Diseases - drug therapy ; Kidneys ; Kinases ; Magnesium ; magnesium lithospermate B ; Male ; MAP kinase ; Mitogen-Activated Protein Kinases - metabolism ; NAD(P)H oxidase ; NADPH Oxidases - metabolism ; NADPH-diaphorase ; NF-kappa B - metabolism ; NF-κB protein ; Nicotinamide ; Nicotinamide adenine dinucleotide ; Nitric oxide ; Nitric-oxide synthase ; NOX4 protein ; Oral administration ; Oxidase ; Oxidative stress ; Oxidative Stress - drug effects ; p53 Protein ; Phosphates ; Protein kinase ; Proteins ; Rats ; Rats, Sprague-Dawley ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; renal damage ; Renal function ; Rodents ; Salvia miltiorrhiza ; Salvia miltiorrhiza - chemistry ; Senescence ; Structural proteins ; Urea</subject><ispartof>Phytotherapy research, 2017-05, Vol.31 (5), p.721-728</ispartof><rights>Copyright © 2017 John Wiley &amp; Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0003-2423-1973 ; 0000-0002-3215-8828</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fptr.5789$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.5789$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28211114$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Chan Hum</creatorcontrib><creatorcontrib>Shin, Sung Ho</creatorcontrib><creatorcontrib>Lee, Eun Kyeong</creatorcontrib><creatorcontrib>Kim, Dae Hyun</creatorcontrib><creatorcontrib>Kim, Min‐Jo</creatorcontrib><creatorcontrib>Roh, Seong‐Soo</creatorcontrib><creatorcontrib>Yokozawa, Takako</creatorcontrib><creatorcontrib>Chung, Hae Young</creatorcontrib><title>Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging‐Induced Renal Inflammation and Senescence via NADPH Oxidase‐Mediated Reactive Oxygen Generation</title><title>Phytotherapy research</title><addtitle>Phytother Res</addtitle><description>The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age‐related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2‐ or 8‐mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22phox), phospho‐p38, nuclear factor‐kappa B p65, cyclooxygenase‐2, and inducible nitric oxide synthase. In addition, MLB‐treated old rats showed lower levels of senescence‐related proteins such as p16, ADP‐ribosylation factor 6, p53, and p21 through effects on the mitogen‐activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age‐related increase in serum urea nitrogen, reflecting renal dysfunction, up‐regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley &amp; Sons, Ltd.</description><subject>Adenosine diphosphate</subject><subject>ADP-ribosylation</subject><subject>ADP-ribosylation factor 6</subject><subject>ADP-Ribosylation Factors</subject><subject>Aging</subject><subject>Aging (artificial)</subject><subject>Aging - drug effects</subject><subject>Aging - physiology</subject><subject>Animals</subject><subject>Body weight</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Cyclooxygenase-2</subject><subject>Drugs, Chinese Herbal - chemistry</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Fuel consumption</subject><subject>GTP-binding protein</subject><subject>inflammation</subject><subject>Inflammation - metabolism</subject><subject>Injury prevention</subject><subject>Kidney Diseases - drug therapy</subject><subject>Kidneys</subject><subject>Kinases</subject><subject>Magnesium</subject><subject>magnesium lithospermate B</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>NAD(P)H oxidase</subject><subject>NADPH Oxidases - metabolism</subject><subject>NADPH-diaphorase</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>Nicotinamide</subject><subject>Nicotinamide adenine dinucleotide</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>NOX4 protein</subject><subject>Oral administration</subject><subject>Oxidase</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>p53 Protein</subject><subject>Phosphates</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>renal damage</subject><subject>Renal function</subject><subject>Rodents</subject><subject>Salvia miltiorrhiza</subject><subject>Salvia miltiorrhiza - chemistry</subject><subject>Senescence</subject><subject>Structural proteins</subject><subject>Urea</subject><issn>0951-418X</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkstu1TAQhi1ERU8LEk-ALLFhk-JLnNjL00LbI51e1BaJXeTEk9RV4qR2UjiseASehIfiSXB6YcEC4c1Inu__Z2T_CL2mZI8Swt4Po98TuVTP0IISpRIqcv4cLYgSNEmp_LyNdkK4IYQoRtIXaJtJRuNJF-jniW4cBDt1eG3H6z4M4Ds9At7Hte87fKnbO6txZ9vR9t5f228a70-uAbzsoI1XkQ142VjX_Pr-Y-XMVIHBF-B0i1eubnUX3WzvsHYGX0IcVYGrAM-mp8sP58f47Ks1OkBUn4Cx0W6W62q0dxB7mwYcPoo6f2_zEm3Vug3w6rHuok-HH68OjpP12dHqYLlOBs6lSoyWqiQpp6kgWpmKp5ngtUpFzVVdUS4rCiQrOQeRGl4KKA0XUioDVDKTC76L3j34Dr6_nSCMRWfj5m2rHfRTKKhUOZdUMPUfaKZUJhmXEX37F3rTTz4-VaQUz4iQKWH_pKSiGWUsn6k3j9RUdmCKwdtO-03x9LURSB6AL7aFzZ8-JcUcmSJGppgjU5xfXcyV_waxlbVX</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Park, Chan Hum</creator><creator>Shin, Sung Ho</creator><creator>Lee, Eun Kyeong</creator><creator>Kim, Dae Hyun</creator><creator>Kim, Min‐Jo</creator><creator>Roh, Seong‐Soo</creator><creator>Yokozawa, Takako</creator><creator>Chung, Hae Young</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2423-1973</orcidid><orcidid>https://orcid.org/0000-0002-3215-8828</orcidid></search><sort><creationdate>201705</creationdate><title>Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging‐Induced Renal Inflammation and Senescence via NADPH Oxidase‐Mediated Reactive Oxygen Generation</title><author>Park, Chan Hum ; Shin, Sung Ho ; Lee, Eun Kyeong ; Kim, Dae Hyun ; Kim, Min‐Jo ; Roh, Seong‐Soo ; Yokozawa, Takako ; Chung, Hae Young</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3389-da89b0431450a9dc34653f945f39fc138c1e06b33e54d3b5ebd35889de182d753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adenosine diphosphate</topic><topic>ADP-ribosylation</topic><topic>ADP-ribosylation factor 6</topic><topic>ADP-Ribosylation Factors</topic><topic>Aging</topic><topic>Aging (artificial)</topic><topic>Aging - drug effects</topic><topic>Aging - physiology</topic><topic>Animals</topic><topic>Body weight</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Cyclooxygenase-2</topic><topic>Drugs, Chinese Herbal - chemistry</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Fuel consumption</topic><topic>GTP-binding protein</topic><topic>inflammation</topic><topic>Inflammation - metabolism</topic><topic>Injury prevention</topic><topic>Kidney Diseases - drug therapy</topic><topic>Kidneys</topic><topic>Kinases</topic><topic>Magnesium</topic><topic>magnesium lithospermate B</topic><topic>Male</topic><topic>MAP kinase</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>NAD(P)H oxidase</topic><topic>NADPH Oxidases - metabolism</topic><topic>NADPH-diaphorase</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>Nicotinamide</topic><topic>Nicotinamide adenine dinucleotide</topic><topic>Nitric oxide</topic><topic>Nitric-oxide synthase</topic><topic>NOX4 protein</topic><topic>Oral administration</topic><topic>Oxidase</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>p53 Protein</topic><topic>Phosphates</topic><topic>Protein kinase</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>renal damage</topic><topic>Renal function</topic><topic>Rodents</topic><topic>Salvia miltiorrhiza</topic><topic>Salvia miltiorrhiza - chemistry</topic><topic>Senescence</topic><topic>Structural proteins</topic><topic>Urea</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Chan Hum</creatorcontrib><creatorcontrib>Shin, Sung Ho</creatorcontrib><creatorcontrib>Lee, Eun Kyeong</creatorcontrib><creatorcontrib>Kim, Dae Hyun</creatorcontrib><creatorcontrib>Kim, Min‐Jo</creatorcontrib><creatorcontrib>Roh, Seong‐Soo</creatorcontrib><creatorcontrib>Yokozawa, Takako</creatorcontrib><creatorcontrib>Chung, Hae Young</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium &amp; 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Magnesium lithospermate B was orally administered at a dose of 2‐ or 8‐mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22phox), phospho‐p38, nuclear factor‐kappa B p65, cyclooxygenase‐2, and inducible nitric oxide synthase. In addition, MLB‐treated old rats showed lower levels of senescence‐related proteins such as p16, ADP‐ribosylation factor 6, p53, and p21 through effects on the mitogen‐activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age‐related increase in serum urea nitrogen, reflecting renal dysfunction, up‐regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley &amp; Sons, Ltd.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28211114</pmid><doi>10.1002/ptr.5789</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-2423-1973</orcidid><orcidid>https://orcid.org/0000-0002-3215-8828</orcidid></addata></record>
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subjects Adenosine diphosphate
ADP-ribosylation
ADP-ribosylation factor 6
ADP-Ribosylation Factors
Aging
Aging (artificial)
Aging - drug effects
Aging - physiology
Animals
Body weight
Cyclooxygenase 2 - metabolism
Cyclooxygenase-2
Drugs, Chinese Herbal - chemistry
Drugs, Chinese Herbal - pharmacology
Fuel consumption
GTP-binding protein
inflammation
Inflammation - metabolism
Injury prevention
Kidney Diseases - drug therapy
Kidneys
Kinases
Magnesium
magnesium lithospermate B
Male
MAP kinase
Mitogen-Activated Protein Kinases - metabolism
NAD(P)H oxidase
NADPH Oxidases - metabolism
NADPH-diaphorase
NF-kappa B - metabolism
NF-κB protein
Nicotinamide
Nicotinamide adenine dinucleotide
Nitric oxide
Nitric-oxide synthase
NOX4 protein
Oral administration
Oxidase
Oxidative stress
Oxidative Stress - drug effects
p53 Protein
Phosphates
Protein kinase
Proteins
Rats
Rats, Sprague-Dawley
Reactive oxygen species
Reactive Oxygen Species - metabolism
renal damage
Renal function
Rodents
Salvia miltiorrhiza
Salvia miltiorrhiza - chemistry
Senescence
Structural proteins
Urea
title Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging‐Induced Renal Inflammation and Senescence via NADPH Oxidase‐Mediated Reactive Oxygen Generation
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