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Kuwanon T and Sanggenon a Isolated from Morus alba Exert Anti-Inflammatory Effects by Regulating NF-κB and HO-1/Nrf2 Signaling Pathways in BV2 and RAW264.7 Cells
We previously investigated the methanolic extract of bark and characterized 11 compounds from the extract: kuwanon G ( ), kuwanon E ( ), kuwanon T ( ), sanggenon A ( ), sanggenon M ( ), sanggenol A ( ), mulberofuran B ( ), mulberofuran G ( ), moracin M ( ), moracin O ( ), and norartocarpanone ( ). H...
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| Published in: | Molecules (Basel, Switzerland) Switzerland), 2021-12, Vol.26 (24), p.7642 |
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| container_title | Molecules (Basel, Switzerland) |
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| creator | Ko, Wonmin Liu, Zhiming Kim, Kwan-Woo Dong, Linsha Lee, Hwan Kim, Na Young Lee, Dong-Sung Woo, Eun-Rhan |
| description | We previously investigated the methanolic extract of
bark and characterized 11 compounds from the extract: kuwanon G (
), kuwanon E (
), kuwanon T (
), sanggenon A (
), sanggenon M (
), sanggenol A (
), mulberofuran B (
), mulberofuran G (
), moracin M (
), moracin O (
), and norartocarpanone (
). Herein, we investigated the anti-inflammatory effects of these compounds on microglial cells (BV2) and macrophages (RAW264.7). Among them,
and
markedly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide in these cells, suggesting the anti-inflammatory properties of these two compounds. These compounds inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, and the expression of inducible nitric oxide synthase and cyclooxygenase-2 following LPS stimulation. Pretreatment with
and
inhibited the activation of the nuclear factor kappa B signaling pathway in both cell types. The compounds also induced the expression of heme oxygenase (HO)-1 through the activation of nuclear factor erythroid 2-related factor 2. Suppressing the activity of HO-1 reversed the anti-inflammatory effects caused by pretreatment with
and
, suggesting that the anti-inflammatory effects were regulated by HO-1. Taken together,
and
are potential candidates for developing therapeutic and preventive agents for inflammatory diseases. |
| doi_str_mv | 10.3390/molecules26247642 |
| format | article |
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bark and characterized 11 compounds from the extract: kuwanon G (
), kuwanon E (
), kuwanon T (
), sanggenon A (
), sanggenon M (
), sanggenol A (
), mulberofuran B (
), mulberofuran G (
), moracin M (
), moracin O (
), and norartocarpanone (
). Herein, we investigated the anti-inflammatory effects of these compounds on microglial cells (BV2) and macrophages (RAW264.7). Among them,
and
markedly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide in these cells, suggesting the anti-inflammatory properties of these two compounds. These compounds inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, and the expression of inducible nitric oxide synthase and cyclooxygenase-2 following LPS stimulation. Pretreatment with
and
inhibited the activation of the nuclear factor kappa B signaling pathway in both cell types. The compounds also induced the expression of heme oxygenase (HO)-1 through the activation of nuclear factor erythroid 2-related factor 2. Suppressing the activity of HO-1 reversed the anti-inflammatory effects caused by pretreatment with
and
, suggesting that the anti-inflammatory effects were regulated by HO-1. Taken together,
and
are potential candidates for developing therapeutic and preventive agents for inflammatory diseases.</description><identifier>ISSN: 1420-3049</identifier><identifier>EISSN: 1420-3049</identifier><identifier>DOI: 10.3390/molecules26247642</identifier><identifier>PMID: 34946724</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Anti-inflammatory agents ; Anti-Inflammatory Agents - chemistry ; Anti-Inflammatory Agents - pharmacology ; anti-inflammatory effects ; Bark ; BV2 ; Carbon monoxide ; Chemical compounds ; Cyclooxygenase-2 ; Cytokines ; Cytotoxicity ; Flavonoids ; Flavonoids - chemistry ; Flavonoids - pharmacology ; Heme ; Heme Oxygenase-1 - metabolism ; Homeostasis ; Inflammation ; Inflammatory diseases ; Interleukin 6 ; kuwanon T ; Lipopolysaccharides ; Macrophages ; Membrane Proteins - metabolism ; Mice ; Microglia ; Morus - chemistry ; Morus alba ; NF-E2-Related Factor 2 - metabolism ; NF-kappa B - metabolism ; NF-κB protein ; Nitric oxide ; Nitric-oxide synthase ; Oxidative stress ; Oxygenase ; Pharmacology ; Pretreatment ; Prostaglandin E2 ; RAW 264.7 Cells ; RAW264.7 cells ; sanggenon A ; Signal transduction ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α</subject><ispartof>Molecules (Basel, Switzerland), 2021-12, Vol.26 (24), p.7642</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-15fc5d7cbf5e6f847584a2cb6f3f41942bf70328eac4b000f89cfb87fbcbc1173</citedby><cites>FETCH-LOGICAL-c493t-15fc5d7cbf5e6f847584a2cb6f3f41942bf70328eac4b000f89cfb87fbcbc1173</cites><orcidid>0000-0002-9234-7567 ; 0000-0002-1911-7060</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2612819934/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2612819934?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34946724$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ko, Wonmin</creatorcontrib><creatorcontrib>Liu, Zhiming</creatorcontrib><creatorcontrib>Kim, Kwan-Woo</creatorcontrib><creatorcontrib>Dong, Linsha</creatorcontrib><creatorcontrib>Lee, Hwan</creatorcontrib><creatorcontrib>Kim, Na Young</creatorcontrib><creatorcontrib>Lee, Dong-Sung</creatorcontrib><creatorcontrib>Woo, Eun-Rhan</creatorcontrib><title>Kuwanon T and Sanggenon a Isolated from Morus alba Exert Anti-Inflammatory Effects by Regulating NF-κB and HO-1/Nrf2 Signaling Pathways in BV2 and RAW264.7 Cells</title><title>Molecules (Basel, Switzerland)</title><addtitle>Molecules</addtitle><description>We previously investigated the methanolic extract of
bark and characterized 11 compounds from the extract: kuwanon G (
), kuwanon E (
), kuwanon T (
), sanggenon A (
), sanggenon M (
), sanggenol A (
), mulberofuran B (
), mulberofuran G (
), moracin M (
), moracin O (
), and norartocarpanone (
). Herein, we investigated the anti-inflammatory effects of these compounds on microglial cells (BV2) and macrophages (RAW264.7). Among them,
and
markedly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide in these cells, suggesting the anti-inflammatory properties of these two compounds. These compounds inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, and the expression of inducible nitric oxide synthase and cyclooxygenase-2 following LPS stimulation. Pretreatment with
and
inhibited the activation of the nuclear factor kappa B signaling pathway in both cell types. The compounds also induced the expression of heme oxygenase (HO)-1 through the activation of nuclear factor erythroid 2-related factor 2. Suppressing the activity of HO-1 reversed the anti-inflammatory effects caused by pretreatment with
and
, suggesting that the anti-inflammatory effects were regulated by HO-1. Taken together,
and
are potential candidates for developing therapeutic and preventive agents for inflammatory diseases.</description><subject>Animals</subject><subject>Anti-inflammatory agents</subject><subject>Anti-Inflammatory Agents - chemistry</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>anti-inflammatory effects</subject><subject>Bark</subject><subject>BV2</subject><subject>Carbon monoxide</subject><subject>Chemical compounds</subject><subject>Cyclooxygenase-2</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Flavonoids</subject><subject>Flavonoids - chemistry</subject><subject>Flavonoids - pharmacology</subject><subject>Heme</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Homeostasis</subject><subject>Inflammation</subject><subject>Inflammatory diseases</subject><subject>Interleukin 6</subject><subject>kuwanon T</subject><subject>Lipopolysaccharides</subject><subject>Macrophages</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Microglia</subject><subject>Morus - chemistry</subject><subject>Morus alba</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>Oxidative stress</subject><subject>Oxygenase</subject><subject>Pharmacology</subject><subject>Pretreatment</subject><subject>Prostaglandin E2</subject><subject>RAW 264.7 Cells</subject><subject>RAW264.7 cells</subject><subject>sanggenon A</subject><subject>Signal transduction</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><issn>1420-3049</issn><issn>1420-3049</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNplks1u1DAUhSMEoqXwAGyQJTZs0vpv4niDNB1N6YjSorbA0rpx7DQjx27thDKvw2PwEDwTmZlStbDyzz3n0_X1ybLXBO8zJvFBF5zRgzOJFpSLgtMn2S7hFOcMc_n0wX4ne5HSEmNKOJk8z3YYl7wQlO9mPz8Ot-CDR5cIfI0uwDeNWZ8BLVJw0Jsa2Rg69CnEISFwFaD5DxN7NPV9my-8ddB10Ie4QnNrje4Tqlbo3DTDaG59g06P8t-_Djf047OcHJxGS9FF23hw6_Jn6K9uYZVQ69HhV7rRnU-_0YLvCzQzzqWX2TMLLplXd-te9uVofjk7zk_OPixm05Ncc8n6nEysntRCV3ZiCltyMSk5UF0VlllOJKeVFZjR0oDmFcbYllLbqhS20pUmRLC9bLHl1gGW6jq2HcSVCtCqzUWIjYLYt9oZVeiKAqaCSMo5q6msTSGZrom0Wls-GVnvt6zroepMrY3vI7hH0McV316pJnxXpcAlZ2wEvLsDxHAzmNSrrk16HAd4E4akaDF-LmNCrPt--490GYY4jnejoiWRkvFRRbYqHUNK0dj7ZghW6zSp_9I0et48fMW942982B-i2MhB</recordid><startdate>20211216</startdate><enddate>20211216</enddate><creator>Ko, Wonmin</creator><creator>Liu, Zhiming</creator><creator>Kim, Kwan-Woo</creator><creator>Dong, Linsha</creator><creator>Lee, Hwan</creator><creator>Kim, Na Young</creator><creator>Lee, Dong-Sung</creator><creator>Woo, Eun-Rhan</creator><general>MDPI AG</general><general>MDPI</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>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>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-9234-7567</orcidid><orcidid>https://orcid.org/0000-0002-1911-7060</orcidid></search><sort><creationdate>20211216</creationdate><title>Kuwanon T and Sanggenon a Isolated from Morus alba Exert Anti-Inflammatory Effects by Regulating NF-κB and HO-1/Nrf2 Signaling Pathways in BV2 and RAW264.7 Cells</title><author>Ko, Wonmin ; Liu, Zhiming ; Kim, Kwan-Woo ; Dong, Linsha ; Lee, Hwan ; Kim, Na Young ; Lee, Dong-Sung ; Woo, Eun-Rhan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-15fc5d7cbf5e6f847584a2cb6f3f41942bf70328eac4b000f89cfb87fbcbc1173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Anti-inflammatory agents</topic><topic>Anti-Inflammatory Agents - chemistry</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>anti-inflammatory effects</topic><topic>Bark</topic><topic>BV2</topic><topic>Carbon monoxide</topic><topic>Chemical compounds</topic><topic>Cyclooxygenase-2</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>Flavonoids</topic><topic>Flavonoids - chemistry</topic><topic>Flavonoids - pharmacology</topic><topic>Heme</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Homeostasis</topic><topic>Inflammation</topic><topic>Inflammatory diseases</topic><topic>Interleukin 6</topic><topic>kuwanon T</topic><topic>Lipopolysaccharides</topic><topic>Macrophages</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Microglia</topic><topic>Morus - chemistry</topic><topic>Morus alba</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>Nitric oxide</topic><topic>Nitric-oxide synthase</topic><topic>Oxidative stress</topic><topic>Oxygenase</topic><topic>Pharmacology</topic><topic>Pretreatment</topic><topic>Prostaglandin E2</topic><topic>RAW 264.7 Cells</topic><topic>RAW264.7 cells</topic><topic>sanggenon A</topic><topic>Signal transduction</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ko, Wonmin</creatorcontrib><creatorcontrib>Liu, Zhiming</creatorcontrib><creatorcontrib>Kim, Kwan-Woo</creatorcontrib><creatorcontrib>Dong, Linsha</creatorcontrib><creatorcontrib>Lee, Hwan</creatorcontrib><creatorcontrib>Kim, Na Young</creatorcontrib><creatorcontrib>Lee, Dong-Sung</creatorcontrib><creatorcontrib>Woo, Eun-Rhan</creatorcontrib><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)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</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>PML(ProQuest Medical Library)</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</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>Open Access: DOAJ - Directory of Open Access Journals</collection><jtitle>Molecules (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ko, Wonmin</au><au>Liu, Zhiming</au><au>Kim, Kwan-Woo</au><au>Dong, Linsha</au><au>Lee, Hwan</au><au>Kim, Na Young</au><au>Lee, Dong-Sung</au><au>Woo, Eun-Rhan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kuwanon T and Sanggenon a Isolated from Morus alba Exert Anti-Inflammatory Effects by Regulating NF-κB and HO-1/Nrf2 Signaling Pathways in BV2 and RAW264.7 Cells</atitle><jtitle>Molecules (Basel, Switzerland)</jtitle><addtitle>Molecules</addtitle><date>2021-12-16</date><risdate>2021</risdate><volume>26</volume><issue>24</issue><spage>7642</spage><pages>7642-</pages><issn>1420-3049</issn><eissn>1420-3049</eissn><abstract>We previously investigated the methanolic extract of
bark and characterized 11 compounds from the extract: kuwanon G (
), kuwanon E (
), kuwanon T (
), sanggenon A (
), sanggenon M (
), sanggenol A (
), mulberofuran B (
), mulberofuran G (
), moracin M (
), moracin O (
), and norartocarpanone (
). Herein, we investigated the anti-inflammatory effects of these compounds on microglial cells (BV2) and macrophages (RAW264.7). Among them,
and
markedly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide in these cells, suggesting the anti-inflammatory properties of these two compounds. These compounds inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, and the expression of inducible nitric oxide synthase and cyclooxygenase-2 following LPS stimulation. Pretreatment with
and
inhibited the activation of the nuclear factor kappa B signaling pathway in both cell types. The compounds also induced the expression of heme oxygenase (HO)-1 through the activation of nuclear factor erythroid 2-related factor 2. Suppressing the activity of HO-1 reversed the anti-inflammatory effects caused by pretreatment with
and
, suggesting that the anti-inflammatory effects were regulated by HO-1. Taken together,
and
are potential candidates for developing therapeutic and preventive agents for inflammatory diseases.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>34946724</pmid><doi>10.3390/molecules26247642</doi><orcidid>https://orcid.org/0000-0002-9234-7567</orcidid><orcidid>https://orcid.org/0000-0002-1911-7060</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecules (Basel, Switzerland), 2021-12, Vol.26 (24), p.7642 |
| issn | 1420-3049 1420-3049 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_6cb2a027192443d29de693cd19fccf45 |
| source | Open Access: PubMed Central; Publicly Available Content Database (Proquest) (PQ_SDU_P3) |
| subjects | Animals Anti-inflammatory agents Anti-Inflammatory Agents - chemistry Anti-Inflammatory Agents - pharmacology anti-inflammatory effects Bark BV2 Carbon monoxide Chemical compounds Cyclooxygenase-2 Cytokines Cytotoxicity Flavonoids Flavonoids - chemistry Flavonoids - pharmacology Heme Heme Oxygenase-1 - metabolism Homeostasis Inflammation Inflammatory diseases Interleukin 6 kuwanon T Lipopolysaccharides Macrophages Membrane Proteins - metabolism Mice Microglia Morus - chemistry Morus alba NF-E2-Related Factor 2 - metabolism NF-kappa B - metabolism NF-κB protein Nitric oxide Nitric-oxide synthase Oxidative stress Oxygenase Pharmacology Pretreatment Prostaglandin E2 RAW 264.7 Cells RAW264.7 cells sanggenon A Signal transduction Tumor necrosis factor-TNF Tumor necrosis factor-α |
| title | Kuwanon T and Sanggenon a Isolated from Morus alba Exert Anti-Inflammatory Effects by Regulating NF-κB and HO-1/Nrf2 Signaling Pathways in BV2 and RAW264.7 Cells |
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