Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells
Roxb. (AL) has been known for its high content of stilbenoids, especially oxyresveratrol. AL has been used in Thai traditional medicine for centuries. However, the role of AL in regulating inflammation has not been elucidated. Here we investigated the molecular mechanisms underlying the anti-inflamm...
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creator | Hankittichai, Phateep Buacheen, Pensiri Pitchakarn, Pornsiri Na Takuathung, Mingkwan Wikan, Nitwara Smith, Duncan R Potikanond, Saranyapin Nimlamool, Wutigri |
description | Roxb. (AL) has been known for its high content of stilbenoids, especially oxyresveratrol. AL has been used in Thai traditional medicine for centuries. However, the role of AL in regulating inflammation has not been elucidated. Here we investigated the molecular mechanisms underlying the anti-inflammation of AL ethanolic extract in RAW 264.7 murine macrophage cell line. The HPLC results revealed that this plant was rich in oxyresveratrol, and AL ethanolic extract exhibited anti-inflammatory properties. In particular, AL extract decreased lipopolysaccharide (LPS)-mediated production and secretion of cytokines and chemokine, including IL-6, TNF-α, and MCP-1. Consistently, the extract inhibited the production of nitric oxide (NO) in the supernatants of LPS-stimulated cells. Data from the immunofluorescence study showed that AL extract suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. Results from Western blot analysis further confirmed that AL extract strongly prevented the LPS-induced degradation of IκB which is normally required for the activation of NF-κB. The protein expression of iNOS and COX-2 in response to LPS stimulation was significantly decreased with the presence of AL extract. AL extract was found to play an anti-inflammatory role, in part through inhibiting LPS-induced activation of Akt. The extract had negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Specifically, incubation of cells with the extract for only 3 h demonstrated the rapid action of AL extract on inhibiting the phosphorylation of Akt, but not ERK1/2. Longer exposure (24 h) to AL extract was required to mildly reduce the phosphorylation of ERK1/2, p38, and JNK MAPKs. These results indicate that AL extract manipulates its anti-inflammatory effects mainly through blocking the PI3K/Akt and NF-κB signal transduction pathways. Collectively, we believe that AL could be a potential alternative agent for alleviating excessive inflammation in many inflammation-associated diseases. |
doi_str_mv | 10.3390/ijms21041355 |
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fullrecord | <record><control><sourceid>pubmed_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_b2cd8deb75de45f0812ea41441733cbd</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_b2cd8deb75de45f0812ea41441733cbd</doaj_id><sourcerecordid>32079307</sourcerecordid><originalsourceid>FETCH-LOGICAL-c450t-c17039a68d6eccba82811d3ad2274ca3c905c6fc9b96a8338577efe7389f9b193</originalsourceid><addsrcrecordid>eNpVkVtr3DAQhUVpaC7tW5-LfkCd6GbLeiksyyZZ2JKSpPRRjEfyrre2ZSRvSP593GwaNk8zzJz5Bs4h5Ctn51IadtFsuyQ4U1zm-QdywpUQGWOF_njQH5PTlLaMCSly84kcS8G0kUyfEDeLY0CIwy7RFv6GgBugi8cxAo502W-aqhkTXf26y5a926F307BuoetgDPGJ3vo0hD552vT0dvaHikKda_oTMIZhA2tP575t02dyVEOb_JfXekZ-Xy7u59fZ6uZqOZ-tMlQ5GzPkmkkDRekKj1hBKUrOnQQnhFYIEg3LsajRVKaAUsoy19rXXsvS1KbiRp6R5Z7rAmztEJsO4pMN0NiXQYhrC3FssPW2EuhK5yudO6_ympVceFBcKa6lxMpNrB971rCrOu_Q95Mn7Tvo-03fbOw6PFjNtDBcTYDve8DkRUrR12-3nNl_ydnD5Cb5t8N_b-L_Uclnn22VaA</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells</title><source>MEDLINE</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Hankittichai, Phateep ; Buacheen, Pensiri ; Pitchakarn, Pornsiri ; Na Takuathung, Mingkwan ; Wikan, Nitwara ; Smith, Duncan R ; Potikanond, Saranyapin ; Nimlamool, Wutigri</creator><creatorcontrib>Hankittichai, Phateep ; Buacheen, Pensiri ; Pitchakarn, Pornsiri ; Na Takuathung, Mingkwan ; Wikan, Nitwara ; Smith, Duncan R ; Potikanond, Saranyapin ; Nimlamool, Wutigri</creatorcontrib><description>Roxb. (AL) has been known for its high content of stilbenoids, especially oxyresveratrol. AL has been used in Thai traditional medicine for centuries. However, the role of AL in regulating inflammation has not been elucidated. Here we investigated the molecular mechanisms underlying the anti-inflammation of AL ethanolic extract in RAW 264.7 murine macrophage cell line. The HPLC results revealed that this plant was rich in oxyresveratrol, and AL ethanolic extract exhibited anti-inflammatory properties. In particular, AL extract decreased lipopolysaccharide (LPS)-mediated production and secretion of cytokines and chemokine, including IL-6, TNF-α, and MCP-1. Consistently, the extract inhibited the production of nitric oxide (NO) in the supernatants of LPS-stimulated cells. Data from the immunofluorescence study showed that AL extract suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. Results from Western blot analysis further confirmed that AL extract strongly prevented the LPS-induced degradation of IκB which is normally required for the activation of NF-κB. The protein expression of iNOS and COX-2 in response to LPS stimulation was significantly decreased with the presence of AL extract. AL extract was found to play an anti-inflammatory role, in part through inhibiting LPS-induced activation of Akt. The extract had negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Specifically, incubation of cells with the extract for only 3 h demonstrated the rapid action of AL extract on inhibiting the phosphorylation of Akt, but not ERK1/2. Longer exposure (24 h) to AL extract was required to mildly reduce the phosphorylation of ERK1/2, p38, and JNK MAPKs. These results indicate that AL extract manipulates its anti-inflammatory effects mainly through blocking the PI3K/Akt and NF-κB signal transduction pathways. Collectively, we believe that AL could be a potential alternative agent for alleviating excessive inflammation in many inflammation-associated diseases.</description><identifier>ISSN: 1422-0067</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21041355</identifier><identifier>PMID: 32079307</identifier><language>eng</language><publisher>Switzerland: MDPI</publisher><subject>akt activation ; Animals ; anti-inflammation ; Anti-Inflammatory Agents - pharmacology ; Artocarpus - chemistry ; artocarpus lakoocha ; Cell Survival - drug effects ; Cyclooxygenase 2 - metabolism ; Cytokines - metabolism ; Inflammation - metabolism ; inflammatory cytokines ; Lipopolysaccharides - adverse effects ; macrophage cells ; Macrophages - drug effects ; Macrophages - metabolism ; Mice ; Mitogen-Activated Protein Kinases - metabolism ; NF-kappa B - metabolism ; Nitric Oxide - metabolism ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Plant Extracts - pharmacology ; RAW 264.7 Cells ; Signal Transduction - drug effects ; Stilbenes - pharmacology</subject><ispartof>International journal of molecular sciences, 2020-02, Vol.21 (4), p.1355</ispartof><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-c17039a68d6eccba82811d3ad2274ca3c905c6fc9b96a8338577efe7389f9b193</citedby><cites>FETCH-LOGICAL-c450t-c17039a68d6eccba82811d3ad2274ca3c905c6fc9b96a8338577efe7389f9b193</cites><orcidid>0000-0002-3777-0848 ; 0000-0002-6592-9852 ; 0000-0002-6219-386X ; 0000-0001-8951-8532 ; 0000-0003-4240-5367</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/PMC7072914/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072914/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32079307$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hankittichai, Phateep</creatorcontrib><creatorcontrib>Buacheen, Pensiri</creatorcontrib><creatorcontrib>Pitchakarn, Pornsiri</creatorcontrib><creatorcontrib>Na Takuathung, Mingkwan</creatorcontrib><creatorcontrib>Wikan, Nitwara</creatorcontrib><creatorcontrib>Smith, Duncan R</creatorcontrib><creatorcontrib>Potikanond, Saranyapin</creatorcontrib><creatorcontrib>Nimlamool, Wutigri</creatorcontrib><title>Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Roxb. (AL) has been known for its high content of stilbenoids, especially oxyresveratrol. AL has been used in Thai traditional medicine for centuries. However, the role of AL in regulating inflammation has not been elucidated. Here we investigated the molecular mechanisms underlying the anti-inflammation of AL ethanolic extract in RAW 264.7 murine macrophage cell line. The HPLC results revealed that this plant was rich in oxyresveratrol, and AL ethanolic extract exhibited anti-inflammatory properties. In particular, AL extract decreased lipopolysaccharide (LPS)-mediated production and secretion of cytokines and chemokine, including IL-6, TNF-α, and MCP-1. Consistently, the extract inhibited the production of nitric oxide (NO) in the supernatants of LPS-stimulated cells. Data from the immunofluorescence study showed that AL extract suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. Results from Western blot analysis further confirmed that AL extract strongly prevented the LPS-induced degradation of IκB which is normally required for the activation of NF-κB. The protein expression of iNOS and COX-2 in response to LPS stimulation was significantly decreased with the presence of AL extract. AL extract was found to play an anti-inflammatory role, in part through inhibiting LPS-induced activation of Akt. The extract had negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Specifically, incubation of cells with the extract for only 3 h demonstrated the rapid action of AL extract on inhibiting the phosphorylation of Akt, but not ERK1/2. Longer exposure (24 h) to AL extract was required to mildly reduce the phosphorylation of ERK1/2, p38, and JNK MAPKs. These results indicate that AL extract manipulates its anti-inflammatory effects mainly through blocking the PI3K/Akt and NF-κB signal transduction pathways. Collectively, we believe that AL could be a potential alternative agent for alleviating excessive inflammation in many inflammation-associated diseases.</description><subject>akt activation</subject><subject>Animals</subject><subject>anti-inflammation</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Artocarpus - chemistry</subject><subject>artocarpus lakoocha</subject><subject>Cell Survival - drug effects</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Cytokines - metabolism</subject><subject>Inflammation - metabolism</subject><subject>inflammatory cytokines</subject><subject>Lipopolysaccharides - adverse effects</subject><subject>macrophage cells</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>Nitric Oxide - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Plant Extracts - pharmacology</subject><subject>RAW 264.7 Cells</subject><subject>Signal Transduction - drug effects</subject><subject>Stilbenes - pharmacology</subject><issn>1422-0067</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNpVkVtr3DAQhUVpaC7tW5-LfkCd6GbLeiksyyZZ2JKSpPRRjEfyrre2ZSRvSP593GwaNk8zzJz5Bs4h5Ctn51IadtFsuyQ4U1zm-QdywpUQGWOF_njQH5PTlLaMCSly84kcS8G0kUyfEDeLY0CIwy7RFv6GgBugi8cxAo502W-aqhkTXf26y5a926F307BuoetgDPGJ3vo0hD552vT0dvaHikKda_oTMIZhA2tP575t02dyVEOb_JfXekZ-Xy7u59fZ6uZqOZ-tMlQ5GzPkmkkDRekKj1hBKUrOnQQnhFYIEg3LsajRVKaAUsoy19rXXsvS1KbiRp6R5Z7rAmztEJsO4pMN0NiXQYhrC3FssPW2EuhK5yudO6_ympVceFBcKa6lxMpNrB971rCrOu_Q95Mn7Tvo-03fbOw6PFjNtDBcTYDve8DkRUrR12-3nNl_ydnD5Cb5t8N_b-L_Uclnn22VaA</recordid><startdate>20200217</startdate><enddate>20200217</enddate><creator>Hankittichai, Phateep</creator><creator>Buacheen, Pensiri</creator><creator>Pitchakarn, Pornsiri</creator><creator>Na Takuathung, Mingkwan</creator><creator>Wikan, Nitwara</creator><creator>Smith, Duncan R</creator><creator>Potikanond, Saranyapin</creator><creator>Nimlamool, Wutigri</creator><general>MDPI</general><general>MDPI AG</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>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3777-0848</orcidid><orcidid>https://orcid.org/0000-0002-6592-9852</orcidid><orcidid>https://orcid.org/0000-0002-6219-386X</orcidid><orcidid>https://orcid.org/0000-0001-8951-8532</orcidid><orcidid>https://orcid.org/0000-0003-4240-5367</orcidid></search><sort><creationdate>20200217</creationdate><title>Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells</title><author>Hankittichai, Phateep ; Buacheen, Pensiri ; Pitchakarn, Pornsiri ; Na Takuathung, Mingkwan ; Wikan, Nitwara ; Smith, Duncan R ; Potikanond, Saranyapin ; Nimlamool, Wutigri</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-c17039a68d6eccba82811d3ad2274ca3c905c6fc9b96a8338577efe7389f9b193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>akt activation</topic><topic>Animals</topic><topic>anti-inflammation</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Artocarpus - chemistry</topic><topic>artocarpus lakoocha</topic><topic>Cell Survival - drug effects</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Cytokines - metabolism</topic><topic>Inflammation - metabolism</topic><topic>inflammatory cytokines</topic><topic>Lipopolysaccharides - adverse effects</topic><topic>macrophage cells</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - metabolism</topic><topic>Mice</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>Nitric Oxide - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>Plant Extracts - pharmacology</topic><topic>RAW 264.7 Cells</topic><topic>Signal Transduction - drug effects</topic><topic>Stilbenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hankittichai, Phateep</creatorcontrib><creatorcontrib>Buacheen, Pensiri</creatorcontrib><creatorcontrib>Pitchakarn, Pornsiri</creatorcontrib><creatorcontrib>Na Takuathung, Mingkwan</creatorcontrib><creatorcontrib>Wikan, Nitwara</creatorcontrib><creatorcontrib>Smith, Duncan R</creatorcontrib><creatorcontrib>Potikanond, Saranyapin</creatorcontrib><creatorcontrib>Nimlamool, Wutigri</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hankittichai, Phateep</au><au>Buacheen, Pensiri</au><au>Pitchakarn, Pornsiri</au><au>Na Takuathung, Mingkwan</au><au>Wikan, Nitwara</au><au>Smith, Duncan R</au><au>Potikanond, Saranyapin</au><au>Nimlamool, Wutigri</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-02-17</date><risdate>2020</risdate><volume>21</volume><issue>4</issue><spage>1355</spage><pages>1355-</pages><issn>1422-0067</issn><eissn>1422-0067</eissn><abstract>Roxb. (AL) has been known for its high content of stilbenoids, especially oxyresveratrol. AL has been used in Thai traditional medicine for centuries. However, the role of AL in regulating inflammation has not been elucidated. Here we investigated the molecular mechanisms underlying the anti-inflammation of AL ethanolic extract in RAW 264.7 murine macrophage cell line. The HPLC results revealed that this plant was rich in oxyresveratrol, and AL ethanolic extract exhibited anti-inflammatory properties. In particular, AL extract decreased lipopolysaccharide (LPS)-mediated production and secretion of cytokines and chemokine, including IL-6, TNF-α, and MCP-1. Consistently, the extract inhibited the production of nitric oxide (NO) in the supernatants of LPS-stimulated cells. Data from the immunofluorescence study showed that AL extract suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. Results from Western blot analysis further confirmed that AL extract strongly prevented the LPS-induced degradation of IκB which is normally required for the activation of NF-κB. The protein expression of iNOS and COX-2 in response to LPS stimulation was significantly decreased with the presence of AL extract. AL extract was found to play an anti-inflammatory role, in part through inhibiting LPS-induced activation of Akt. The extract had negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Specifically, incubation of cells with the extract for only 3 h demonstrated the rapid action of AL extract on inhibiting the phosphorylation of Akt, but not ERK1/2. Longer exposure (24 h) to AL extract was required to mildly reduce the phosphorylation of ERK1/2, p38, and JNK MAPKs. These results indicate that AL extract manipulates its anti-inflammatory effects mainly through blocking the PI3K/Akt and NF-κB signal transduction pathways. Collectively, we believe that AL could be a potential alternative agent for alleviating excessive inflammation in many inflammation-associated diseases.</abstract><cop>Switzerland</cop><pub>MDPI</pub><pmid>32079307</pmid><doi>10.3390/ijms21041355</doi><orcidid>https://orcid.org/0000-0002-3777-0848</orcidid><orcidid>https://orcid.org/0000-0002-6592-9852</orcidid><orcidid>https://orcid.org/0000-0002-6219-386X</orcidid><orcidid>https://orcid.org/0000-0001-8951-8532</orcidid><orcidid>https://orcid.org/0000-0003-4240-5367</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | akt activation Animals anti-inflammation Anti-Inflammatory Agents - pharmacology Artocarpus - chemistry artocarpus lakoocha Cell Survival - drug effects Cyclooxygenase 2 - metabolism Cytokines - metabolism Inflammation - metabolism inflammatory cytokines Lipopolysaccharides - adverse effects macrophage cells Macrophages - drug effects Macrophages - metabolism Mice Mitogen-Activated Protein Kinases - metabolism NF-kappa B - metabolism Nitric Oxide - metabolism Phosphatidylinositol 3-Kinases - metabolism Phosphorylation Plant Extracts - pharmacology RAW 264.7 Cells Signal Transduction - drug effects Stilbenes - pharmacology |
title | Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells |
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