Protective Effects of Two Safflower Derived Compounds, Kaempferol and Hydroxysafflor Yellow A, on Hyperglycaemic Stress-Induced Podocyte Apoptosis via Modulating of Macrophage M1/M2 Polarization

Objective. The primary initiating mechanism in diabetes nephropathy (DN) is hyperglycemia-induced inflammation in which macrophage and podocyte play important roles. The present research is aimed at exploring the effects of kaempferol (Ka) and hydroxysafflor yellow A (HSYA) on classically activated...

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Veröffentlicht in:Journal of Immunology Research 2020-10, Vol.2020 (2020), p.1-11, Article 2462039
Hauptverfasser: Zhao, Xiaoyun, Zhang, Xilan, Shen, Dayue, Zheng, Dan, Li, Yuanping, Liao, Hui
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container_issue 2020
container_start_page 1
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creator Zhao, Xiaoyun
Zhang, Xilan
Shen, Dayue
Zheng, Dan
Li, Yuanping
Liao, Hui
description Objective. The primary initiating mechanism in diabetes nephropathy (DN) is hyperglycemia-induced inflammation in which macrophage and podocyte play important roles. The present research is aimed at exploring the effects of kaempferol (Ka) and hydroxysafflor yellow A (HSYA) on classically activated (M1)/alternatively activated (M2) macrophage polarization and podocyte apoptosis under hyperglycaemic conditions in vitro. Methods. (1) RAW264.7 cells were treated with 11.1 mM glucose (NG), 33.3 mM glucose (HG), Ka 4–8 μM, and HSYA 100–200 μM separately. The expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 were quantified by Western blotting and real-time quantitative PCR. The collected supernatants from macrophage were named as (NG) MS, (HG) MS, (Ka) MS, and (HSYA) MS. (2) The podocyte survival rate was assessed by Bromodeoxyuridine assay, while TNF-α and interleukin- (IL-) 1β levels were evaluated by Elisa. Results. (1) Compared to the HG group, the Ka and HSYA 100 μM groups decreased iNOS and TNF-α levels and increased Arg-1 and CD206 expressions significantly (protein and mRNA: p
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The primary initiating mechanism in diabetes nephropathy (DN) is hyperglycemia-induced inflammation in which macrophage and podocyte play important roles. The present research is aimed at exploring the effects of kaempferol (Ka) and hydroxysafflor yellow A (HSYA) on classically activated (M1)/alternatively activated (M2) macrophage polarization and podocyte apoptosis under hyperglycaemic conditions in vitro. Methods. (1) RAW264.7 cells were treated with 11.1 mM glucose (NG), 33.3 mM glucose (HG), Ka 4–8 μM, and HSYA 100–200 μM separately. The expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 were quantified by Western blotting and real-time quantitative PCR. The collected supernatants from macrophage were named as (NG) MS, (HG) MS, (Ka) MS, and (HSYA) MS. (2) The podocyte survival rate was assessed by Bromodeoxyuridine assay, while TNF-α and interleukin- (IL-) 1β levels were evaluated by Elisa. Results. (1) Compared to the HG group, the Ka and HSYA 100 μM groups decreased iNOS and TNF-α levels and increased Arg-1 and CD206 expressions significantly (protein and mRNA: p&lt;0.05, respectively). (2) The podocyte survival rate of Ka 8 μM was higher than that of HG, and the rates of (Ka) MS and (HSYA 100 μM) MS were higher than that of (HG) MS significantly (all: p&lt;0.05). (3) TNF-α and IL-1β levels of Ka and HSYA 100 μM were significantly lower than those of the HG group, and both levels in the (Ka) MS and (HSYA) MS were lower than those in the (HG) MS group significantly (p&lt;0.05, respectively). Conclusion. The protective effects of Ka and HSYA on podocyte apoptosis under hyperglycemic stress are related to their modulation on M1/M2 polarization and the lowering effects on TNF-α and IL-1β levels.</description><identifier>ISSN: 2314-8861</identifier><identifier>EISSN: 2314-7156</identifier><identifier>DOI: 10.1155/2020/2462039</identifier><identifier>PMID: 33102606</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Animals ; Antibodies ; Apoptosis ; Arginase ; Bromodeoxyuridine ; Carthamus tinctorius - immunology ; Cell Differentiation ; Cells, Cultured ; Chalcone - analogs &amp; derivatives ; Chalcone - therapeutic use ; Chinese medicine ; Cytokines - metabolism ; Dextrose ; Diabetes ; Diabetes mellitus ; Glucose ; Humans ; Hyperglycemia ; Hyperglycemia - drug therapy ; IL-1β ; Immunology ; Immunomodulation ; Inflammation ; Instrument industry ; Interleukins ; Kaempferol ; Kaempferols - therapeutic use ; Laboratories ; Life Sciences &amp; Biomedicine ; Macrophages ; Macrophages - immunology ; Mannose ; Membranes ; Mice ; mRNA ; Nephropathy ; Nitric oxide ; Nitric-oxide synthase ; Podocytes - physiology ; Polarization ; Proteins ; Quinones - therapeutic use ; RAW 264.7 Cells ; RNA ; Science &amp; Technology ; Stress, Physiological ; Th1 Cells - immunology ; Th2 Cells - immunology ; Tumor necrosis factor ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Western blotting</subject><ispartof>Journal of Immunology Research, 2020-10, Vol.2020 (2020), p.1-11, Article 2462039</ispartof><rights>Copyright © 2020 Yuanping Li et al.</rights><rights>COPYRIGHT 2020 John Wiley &amp; Sons, Inc.</rights><rights>Copyright © 2020 Yuanping Li et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Yuanping Li et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>18</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000582216100001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c635t-f8464c06a6103fc86e5ef443cff4856e02a806891e5c49dd658bbc119baf60b83</citedby><cites>FETCH-LOGICAL-c635t-f8464c06a6103fc86e5ef443cff4856e02a806891e5c49dd658bbc119baf60b83</cites><orcidid>0000-0002-3631-4015 ; 0000-0002-6940-0788 ; 0000-0001-8095-811X ; 0000-0001-6325-062X ; 0000-0003-2667-1809 ; 0000-0002-5692-5729</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569436/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569436/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,878,886,2103,2115,27929,27930,28253,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33102606$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Wang, Kai</contributor><contributor>Kai Wang</contributor><creatorcontrib>Zhao, Xiaoyun</creatorcontrib><creatorcontrib>Zhang, Xilan</creatorcontrib><creatorcontrib>Shen, Dayue</creatorcontrib><creatorcontrib>Zheng, Dan</creatorcontrib><creatorcontrib>Li, Yuanping</creatorcontrib><creatorcontrib>Liao, Hui</creatorcontrib><title>Protective Effects of Two Safflower Derived Compounds, Kaempferol and Hydroxysafflor Yellow A, on Hyperglycaemic Stress-Induced Podocyte Apoptosis via Modulating of Macrophage M1/M2 Polarization</title><title>Journal of Immunology Research</title><addtitle>J IMMUNOL RES</addtitle><addtitle>J Immunol Res</addtitle><description>Objective. The primary initiating mechanism in diabetes nephropathy (DN) is hyperglycemia-induced inflammation in which macrophage and podocyte play important roles. The present research is aimed at exploring the effects of kaempferol (Ka) and hydroxysafflor yellow A (HSYA) on classically activated (M1)/alternatively activated (M2) macrophage polarization and podocyte apoptosis under hyperglycaemic conditions in vitro. Methods. (1) RAW264.7 cells were treated with 11.1 mM glucose (NG), 33.3 mM glucose (HG), Ka 4–8 μM, and HSYA 100–200 μM separately. The expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 were quantified by Western blotting and real-time quantitative PCR. The collected supernatants from macrophage were named as (NG) MS, (HG) MS, (Ka) MS, and (HSYA) MS. (2) The podocyte survival rate was assessed by Bromodeoxyuridine assay, while TNF-α and interleukin- (IL-) 1β levels were evaluated by Elisa. Results. (1) Compared to the HG group, the Ka and HSYA 100 μM groups decreased iNOS and TNF-α levels and increased Arg-1 and CD206 expressions significantly (protein and mRNA: p&lt;0.05, respectively). (2) The podocyte survival rate of Ka 8 μM was higher than that of HG, and the rates of (Ka) MS and (HSYA 100 μM) MS were higher than that of (HG) MS significantly (all: p&lt;0.05). (3) TNF-α and IL-1β levels of Ka and HSYA 100 μM were significantly lower than those of the HG group, and both levels in the (Ka) MS and (HSYA) MS were lower than those in the (HG) MS group significantly (p&lt;0.05, respectively). Conclusion. The protective effects of Ka and HSYA on podocyte apoptosis under hyperglycemic stress are related to their modulation on M1/M2 polarization and the lowering effects on TNF-α and IL-1β levels.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Arginase</subject><subject>Bromodeoxyuridine</subject><subject>Carthamus tinctorius - immunology</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Chalcone - analogs &amp; derivatives</subject><subject>Chalcone - therapeutic use</subject><subject>Chinese medicine</subject><subject>Cytokines - metabolism</subject><subject>Dextrose</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Glucose</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Hyperglycemia - drug therapy</subject><subject>IL-1β</subject><subject>Immunology</subject><subject>Immunomodulation</subject><subject>Inflammation</subject><subject>Instrument industry</subject><subject>Interleukins</subject><subject>Kaempferol</subject><subject>Kaempferols - therapeutic use</subject><subject>Laboratories</subject><subject>Life Sciences &amp; Biomedicine</subject><subject>Macrophages</subject><subject>Macrophages - immunology</subject><subject>Mannose</subject><subject>Membranes</subject><subject>Mice</subject><subject>mRNA</subject><subject>Nephropathy</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>Podocytes - physiology</subject><subject>Polarization</subject><subject>Proteins</subject><subject>Quinones - therapeutic use</subject><subject>RAW 264.7 Cells</subject><subject>RNA</subject><subject>Science &amp; Technology</subject><subject>Stress, Physiological</subject><subject>Th1 Cells - immunology</subject><subject>Th2 Cells - immunology</subject><subject>Tumor necrosis factor</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Western blotting</subject><issn>2314-8861</issn><issn>2314-7156</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1v0zAUhiMEYtPYHdfIEhJCYt38kTjODVJVBptYxaSNC64ixx-tp9QOdrJSfh6_jNO1bCviguQils_zvnbOebPsJcHHhBTFCcUUn9CcU8yqJ9k-ZSQflaTgT7drITjZyw5Tcg0ucMkYF_x5tscYwZRjvp_9uoyhN6p3twadWgurhIJF18uArqS1bViaiD6YCHWNJmHRhcHrdIQ-S7PorImhRdJrdLbSMfxYpTtJRN9MC0o0PkLBQ60zcdauFEicQld9NCmNzr0eFHheBh3Uqjdo3IWuD8kldOskmgY9tLJ3fra-zlSqGLq5nBk0JSdTCqpWRvcTgOBfZM-sbJM53H4Psq8fT68nZ6OLL5_OJ-OLkeKs6EdW5DxXmEtOMLNKcFMYm-dMWZuLghtMpcBcVMQUKq-05oVoGkVI1UjLcSPYQXa-8dVB3tRddAsZV3WQrr7bCHFWy9g71ZraVpXSjbZUWZo3ohEltQwmULKSyFJY8Hq_8eqGZmG0Mr6Pst0x3a14N69n4bYuC17ljIPB261BDN8Hk_p64ZKCtktvwpBqmhd5TiiMGdDXf6E3YYgeWrWmSFlgTtgDNZPwA87bAOeqtWk95lWJK-gHAer4HxS8ej3b4I11sL8jePNIMDey7ecptMN6cGkXPNqAMOmUorH3zSC4Xme9Xme93mYd8FePG3gP_0k2AGIDLE0TbFLOeGXuMYxxISglkAV4yMT1d1GaQLp7kL77f-kDPXdey6X7z3sbYIyVDzQRJSYl-w3wyDHl</recordid><startdate>20201010</startdate><enddate>20201010</enddate><creator>Zhao, Xiaoyun</creator><creator>Zhang, Xilan</creator><creator>Shen, Dayue</creator><creator>Zheng, Dan</creator><creator>Li, Yuanping</creator><creator>Liao, Hui</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>Hindawi Publishing Group</general><general>John Wiley &amp; 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Biomedicine</topic><topic>Macrophages</topic><topic>Macrophages - immunology</topic><topic>Mannose</topic><topic>Membranes</topic><topic>Mice</topic><topic>mRNA</topic><topic>Nephropathy</topic><topic>Nitric oxide</topic><topic>Nitric-oxide synthase</topic><topic>Podocytes - physiology</topic><topic>Polarization</topic><topic>Proteins</topic><topic>Quinones - therapeutic use</topic><topic>RAW 264.7 Cells</topic><topic>RNA</topic><topic>Science &amp; Technology</topic><topic>Stress, Physiological</topic><topic>Th1 Cells - immunology</topic><topic>Th2 Cells - immunology</topic><topic>Tumor necrosis factor</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Xiaoyun</creatorcontrib><creatorcontrib>Zhang, Xilan</creatorcontrib><creatorcontrib>Shen, Dayue</creatorcontrib><creatorcontrib>Zheng, Dan</creatorcontrib><creatorcontrib>Li, Yuanping</creatorcontrib><creatorcontrib>Liao, Hui</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</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>Immunology Abstracts</collection><collection>Health &amp; 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Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</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>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Journal of Immunology Research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Xiaoyun</au><au>Zhang, Xilan</au><au>Shen, Dayue</au><au>Zheng, Dan</au><au>Li, Yuanping</au><au>Liao, Hui</au><au>Wang, Kai</au><au>Kai Wang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective Effects of Two Safflower Derived Compounds, Kaempferol and Hydroxysafflor Yellow A, on Hyperglycaemic Stress-Induced Podocyte Apoptosis via Modulating of Macrophage M1/M2 Polarization</atitle><jtitle>Journal of Immunology Research</jtitle><stitle>J IMMUNOL RES</stitle><addtitle>J Immunol Res</addtitle><date>2020-10-10</date><risdate>2020</risdate><volume>2020</volume><issue>2020</issue><spage>1</spage><epage>11</epage><pages>1-11</pages><artnum>2462039</artnum><issn>2314-8861</issn><eissn>2314-7156</eissn><abstract>Objective. The primary initiating mechanism in diabetes nephropathy (DN) is hyperglycemia-induced inflammation in which macrophage and podocyte play important roles. The present research is aimed at exploring the effects of kaempferol (Ka) and hydroxysafflor yellow A (HSYA) on classically activated (M1)/alternatively activated (M2) macrophage polarization and podocyte apoptosis under hyperglycaemic conditions in vitro. Methods. (1) RAW264.7 cells were treated with 11.1 mM glucose (NG), 33.3 mM glucose (HG), Ka 4–8 μM, and HSYA 100–200 μM separately. The expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 were quantified by Western blotting and real-time quantitative PCR. The collected supernatants from macrophage were named as (NG) MS, (HG) MS, (Ka) MS, and (HSYA) MS. (2) The podocyte survival rate was assessed by Bromodeoxyuridine assay, while TNF-α and interleukin- (IL-) 1β levels were evaluated by Elisa. Results. (1) Compared to the HG group, the Ka and HSYA 100 μM groups decreased iNOS and TNF-α levels and increased Arg-1 and CD206 expressions significantly (protein and mRNA: p&lt;0.05, respectively). (2) The podocyte survival rate of Ka 8 μM was higher than that of HG, and the rates of (Ka) MS and (HSYA 100 μM) MS were higher than that of (HG) MS significantly (all: p&lt;0.05). (3) TNF-α and IL-1β levels of Ka and HSYA 100 μM were significantly lower than those of the HG group, and both levels in the (Ka) MS and (HSYA) MS were lower than those in the (HG) MS group significantly (p&lt;0.05, respectively). Conclusion. The protective effects of Ka and HSYA on podocyte apoptosis under hyperglycemic stress are related to their modulation on M1/M2 polarization and the lowering effects on TNF-α and IL-1β levels.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>33102606</pmid><doi>10.1155/2020/2462039</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3631-4015</orcidid><orcidid>https://orcid.org/0000-0002-6940-0788</orcidid><orcidid>https://orcid.org/0000-0001-8095-811X</orcidid><orcidid>https://orcid.org/0000-0001-6325-062X</orcidid><orcidid>https://orcid.org/0000-0003-2667-1809</orcidid><orcidid>https://orcid.org/0000-0002-5692-5729</orcidid><oa>free_for_read</oa></addata></record>
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subjects Animals
Antibodies
Apoptosis
Arginase
Bromodeoxyuridine
Carthamus tinctorius - immunology
Cell Differentiation
Cells, Cultured
Chalcone - analogs & derivatives
Chalcone - therapeutic use
Chinese medicine
Cytokines - metabolism
Dextrose
Diabetes
Diabetes mellitus
Glucose
Humans
Hyperglycemia
Hyperglycemia - drug therapy
IL-1β
Immunology
Immunomodulation
Inflammation
Instrument industry
Interleukins
Kaempferol
Kaempferols - therapeutic use
Laboratories
Life Sciences & Biomedicine
Macrophages
Macrophages - immunology
Mannose
Membranes
Mice
mRNA
Nephropathy
Nitric oxide
Nitric-oxide synthase
Podocytes - physiology
Polarization
Proteins
Quinones - therapeutic use
RAW 264.7 Cells
RNA
Science & Technology
Stress, Physiological
Th1 Cells - immunology
Th2 Cells - immunology
Tumor necrosis factor
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Western blotting
title Protective Effects of Two Safflower Derived Compounds, Kaempferol and Hydroxysafflor Yellow A, on Hyperglycaemic Stress-Induced Podocyte Apoptosis via Modulating of Macrophage M1/M2 Polarization
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