Betulin isolated from Pyrola incarnata Fisch. inhibited lipopolysaccharide (LPS)-induced neuroinflammation with the guidance of computer-aided drug design
[Display omitted] •Ten compounds including betulin were isolated from P. incarnata and elucidated.•Betulin suppressed LPS-induced activation by inhibiting inflammatory cytokines.•Molecular docking suggested possible anti-inflammatory mechanism of betulin.•Betulin reduced iNOS expression, prevented J...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2020-06, Vol.30 (12), p.127193-127193, Article 127193 |
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| creator | Liu, Qian Liu, Jin-Ping Mei, Jia-Hui Li, Shuang-Jun Shi, Li-Qiao Lin, Zong-Hao Xie, Bai-Yan Sun, Wei-Guang Wang, Zhen-Yu Yang, Xi-Liang Zou, Yu Fang, Wei |
| description | [Display omitted]
•Ten compounds including betulin were isolated from P. incarnata and elucidated.•Betulin suppressed LPS-induced activation by inhibiting inflammatory cytokines.•Molecular docking suggested possible anti-inflammatory mechanism of betulin.•Betulin reduced iNOS expression, prevented JNKs and phosphorylation of NF-κB/p65.
This study aims to investigate active phytochemicals isolated from Pyrola incarnata Fisch. (P. incarnata) and their protection against neuroinflammation induced by LPS. Betulin, accompanied with other 9 compounds, were isolated from P. incarnata and elucidated by spectroscopic analysis (1H-, 13C NMR). ELISA kits and the measurement of NO production based on Griess reaction showed that betulin (5) (250 μg/mL) could suppress LPS-induced activation of microglial cell BV-2 better than others by inhibiting inflammatory cytokines (TNF-α, IL-6, IL-1β) expression and NO production. With the guidance of computer-aided drug design and the analysis of biological experiment, we demonstrated betulin could reduce LPS-induced iNOS expression, prevent JNKs pathways, and down-regulate the phosphorylation levels of NF-κB/p65. In conclusion, betulin isolated from P. incarnata possessed outstanding anti-neuroinflammation potential, presumably related to iNOS expression, JNKs and NF-κB/p65 pathways. Therefore, Pyrola incarnata may be a valuable natural resource and betulin is a potential drug for the treatment of neurodegenerative disorders by inhibiting inflammatory mediators. |
| doi_str_mv | 10.1016/j.bmcl.2020.127193 |
| format | Article |
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•Ten compounds including betulin were isolated from P. incarnata and elucidated.•Betulin suppressed LPS-induced activation by inhibiting inflammatory cytokines.•Molecular docking suggested possible anti-inflammatory mechanism of betulin.•Betulin reduced iNOS expression, prevented JNKs and phosphorylation of NF-κB/p65.
This study aims to investigate active phytochemicals isolated from Pyrola incarnata Fisch. (P. incarnata) and their protection against neuroinflammation induced by LPS. Betulin, accompanied with other 9 compounds, were isolated from P. incarnata and elucidated by spectroscopic analysis (1H-, 13C NMR). ELISA kits and the measurement of NO production based on Griess reaction showed that betulin (5) (250 μg/mL) could suppress LPS-induced activation of microglial cell BV-2 better than others by inhibiting inflammatory cytokines (TNF-α, IL-6, IL-1β) expression and NO production. With the guidance of computer-aided drug design and the analysis of biological experiment, we demonstrated betulin could reduce LPS-induced iNOS expression, prevent JNKs pathways, and down-regulate the phosphorylation levels of NF-κB/p65. In conclusion, betulin isolated from P. incarnata possessed outstanding anti-neuroinflammation potential, presumably related to iNOS expression, JNKs and NF-κB/p65 pathways. Therefore, Pyrola incarnata may be a valuable natural resource and betulin is a potential drug for the treatment of neurodegenerative disorders by inhibiting inflammatory mediators.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2020.127193</identifier><identifier>PMID: 32334913</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Betulin ; Cell Line ; Dose-Response Relationship, Drug ; Drug Design ; Inflammation - drug therapy ; Inflammation Mediators - chemistry ; Inflammation Mediators - isolation & purification ; Inflammation Mediators - pharmacology ; Lipopolysaccharide ; Lipopolysaccharides - antagonists & inhibitors ; Lipopolysaccharides - pharmacology ; Mice ; Microglia cells ; Molecular Conformation ; Neuroinflammation ; Nitric Oxide - antagonists & inhibitors ; Nitric Oxide - biosynthesis ; Nitric Oxide Synthase Type II - antagonists & inhibitors ; Nitric Oxide Synthase Type II - metabolism ; Pyrola - chemistry ; Pyrola incarnata ; Stereoisomerism ; Structure-Activity Relationship ; Triterpenes - chemistry ; Triterpenes - isolation & purification ; Triterpenes - pharmacology</subject><ispartof>Bioorganic & medicinal chemistry letters, 2020-06, Vol.30 (12), p.127193-127193, Article 127193</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-97be9e42d04cbd97e65873a268479d09245c70042eee802009d722f8bcf382793</citedby><cites>FETCH-LOGICAL-c356t-97be9e42d04cbd97e65873a268479d09245c70042eee802009d722f8bcf382793</cites><orcidid>0000-0002-4473-7122 ; 0000-0002-9797-7429</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X20302924$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32334913$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Qian</creatorcontrib><creatorcontrib>Liu, Jin-Ping</creatorcontrib><creatorcontrib>Mei, Jia-Hui</creatorcontrib><creatorcontrib>Li, Shuang-Jun</creatorcontrib><creatorcontrib>Shi, Li-Qiao</creatorcontrib><creatorcontrib>Lin, Zong-Hao</creatorcontrib><creatorcontrib>Xie, Bai-Yan</creatorcontrib><creatorcontrib>Sun, Wei-Guang</creatorcontrib><creatorcontrib>Wang, Zhen-Yu</creatorcontrib><creatorcontrib>Yang, Xi-Liang</creatorcontrib><creatorcontrib>Zou, Yu</creatorcontrib><creatorcontrib>Fang, Wei</creatorcontrib><title>Betulin isolated from Pyrola incarnata Fisch. inhibited lipopolysaccharide (LPS)-induced neuroinflammation with the guidance of computer-aided drug design</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
•Ten compounds including betulin were isolated from P. incarnata and elucidated.•Betulin suppressed LPS-induced activation by inhibiting inflammatory cytokines.•Molecular docking suggested possible anti-inflammatory mechanism of betulin.•Betulin reduced iNOS expression, prevented JNKs and phosphorylation of NF-κB/p65.
This study aims to investigate active phytochemicals isolated from Pyrola incarnata Fisch. (P. incarnata) and their protection against neuroinflammation induced by LPS. Betulin, accompanied with other 9 compounds, were isolated from P. incarnata and elucidated by spectroscopic analysis (1H-, 13C NMR). ELISA kits and the measurement of NO production based on Griess reaction showed that betulin (5) (250 μg/mL) could suppress LPS-induced activation of microglial cell BV-2 better than others by inhibiting inflammatory cytokines (TNF-α, IL-6, IL-1β) expression and NO production. With the guidance of computer-aided drug design and the analysis of biological experiment, we demonstrated betulin could reduce LPS-induced iNOS expression, prevent JNKs pathways, and down-regulate the phosphorylation levels of NF-κB/p65. In conclusion, betulin isolated from P. incarnata possessed outstanding anti-neuroinflammation potential, presumably related to iNOS expression, JNKs and NF-κB/p65 pathways. Therefore, Pyrola incarnata may be a valuable natural resource and betulin is a potential drug for the treatment of neurodegenerative disorders by inhibiting inflammatory mediators.</description><subject>Animals</subject><subject>Betulin</subject><subject>Cell Line</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Design</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation Mediators - chemistry</subject><subject>Inflammation Mediators - isolation & purification</subject><subject>Inflammation Mediators - pharmacology</subject><subject>Lipopolysaccharide</subject><subject>Lipopolysaccharides - antagonists & inhibitors</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Mice</subject><subject>Microglia cells</subject><subject>Molecular Conformation</subject><subject>Neuroinflammation</subject><subject>Nitric Oxide - antagonists & inhibitors</subject><subject>Nitric Oxide - biosynthesis</subject><subject>Nitric Oxide Synthase Type II - antagonists & inhibitors</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Pyrola - chemistry</subject><subject>Pyrola incarnata</subject><subject>Stereoisomerism</subject><subject>Structure-Activity Relationship</subject><subject>Triterpenes - chemistry</subject><subject>Triterpenes - isolation & purification</subject><subject>Triterpenes - pharmacology</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2LFDEQhoMo7jj6BzxIjuuhx3SS_gh4cRdXhQEXVPAW0kn1dIbupM2HMn_FX2uGWT16Kqp46oWqB6GXNdnVpG7fHHfDoucdJbQMaFcL9ghtat7yinHSPEYbIlpS9YJ_v0LPYjwSUnPC-VN0xShjXNRsg37fQMqzddhGP6sEBo_BL_j-FEqLrdMqOJUUvrNRT7symOxgz9hsV7_6-RSV1pMK1gC-3t9_eV1ZZ7IugIMcvHXjrJZFJesd_mXThNME-JCtUU4D9iPWfllzglCpEmGwCfmADUR7cM_Rk1HNEV481C36dvf-6-3Hav_5w6fbd_tKs6ZNlegGEMCpIVwPRnTQNn3HFG173glDBOWN7gjhFAD68ioiTEfp2A96ZD3tBNui60vuGvyPDDHJpRwL86wc-BwlZaKhLalL6hbRC6qDjzHAKNdgFxVOsiby7EQe5dmJPDuRFydl6dVDfh4WMP9W_koowNsLAOXKnxaCjNpC-Y-xAXSSxtv_5f8BSZafag</recordid><startdate>20200615</startdate><enddate>20200615</enddate><creator>Liu, Qian</creator><creator>Liu, Jin-Ping</creator><creator>Mei, Jia-Hui</creator><creator>Li, Shuang-Jun</creator><creator>Shi, Li-Qiao</creator><creator>Lin, Zong-Hao</creator><creator>Xie, Bai-Yan</creator><creator>Sun, Wei-Guang</creator><creator>Wang, Zhen-Yu</creator><creator>Yang, Xi-Liang</creator><creator>Zou, Yu</creator><creator>Fang, Wei</creator><general>Elsevier Ltd</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>7X8</scope><orcidid>https://orcid.org/0000-0002-4473-7122</orcidid><orcidid>https://orcid.org/0000-0002-9797-7429</orcidid></search><sort><creationdate>20200615</creationdate><title>Betulin isolated from Pyrola incarnata Fisch. inhibited lipopolysaccharide (LPS)-induced neuroinflammation with the guidance of computer-aided drug design</title><author>Liu, Qian ; Liu, Jin-Ping ; Mei, Jia-Hui ; Li, Shuang-Jun ; Shi, Li-Qiao ; Lin, Zong-Hao ; Xie, Bai-Yan ; Sun, Wei-Guang ; Wang, Zhen-Yu ; Yang, Xi-Liang ; Zou, Yu ; Fang, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-97be9e42d04cbd97e65873a268479d09245c70042eee802009d722f8bcf382793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Betulin</topic><topic>Cell Line</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Design</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation Mediators - chemistry</topic><topic>Inflammation Mediators - isolation & purification</topic><topic>Inflammation Mediators - pharmacology</topic><topic>Lipopolysaccharide</topic><topic>Lipopolysaccharides - antagonists & inhibitors</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Mice</topic><topic>Microglia cells</topic><topic>Molecular Conformation</topic><topic>Neuroinflammation</topic><topic>Nitric Oxide - antagonists & inhibitors</topic><topic>Nitric Oxide - biosynthesis</topic><topic>Nitric Oxide Synthase Type II - antagonists & inhibitors</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Pyrola - chemistry</topic><topic>Pyrola incarnata</topic><topic>Stereoisomerism</topic><topic>Structure-Activity Relationship</topic><topic>Triterpenes - chemistry</topic><topic>Triterpenes - isolation & purification</topic><topic>Triterpenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Qian</creatorcontrib><creatorcontrib>Liu, Jin-Ping</creatorcontrib><creatorcontrib>Mei, Jia-Hui</creatorcontrib><creatorcontrib>Li, Shuang-Jun</creatorcontrib><creatorcontrib>Shi, Li-Qiao</creatorcontrib><creatorcontrib>Lin, Zong-Hao</creatorcontrib><creatorcontrib>Xie, Bai-Yan</creatorcontrib><creatorcontrib>Sun, Wei-Guang</creatorcontrib><creatorcontrib>Wang, Zhen-Yu</creatorcontrib><creatorcontrib>Yang, Xi-Liang</creatorcontrib><creatorcontrib>Zou, Yu</creatorcontrib><creatorcontrib>Fang, Wei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Qian</au><au>Liu, Jin-Ping</au><au>Mei, Jia-Hui</au><au>Li, Shuang-Jun</au><au>Shi, Li-Qiao</au><au>Lin, Zong-Hao</au><au>Xie, Bai-Yan</au><au>Sun, Wei-Guang</au><au>Wang, Zhen-Yu</au><au>Yang, Xi-Liang</au><au>Zou, Yu</au><au>Fang, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Betulin isolated from Pyrola incarnata Fisch. inhibited lipopolysaccharide (LPS)-induced neuroinflammation with the guidance of computer-aided drug design</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2020-06-15</date><risdate>2020</risdate><volume>30</volume><issue>12</issue><spage>127193</spage><epage>127193</epage><pages>127193-127193</pages><artnum>127193</artnum><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
•Ten compounds including betulin were isolated from P. incarnata and elucidated.•Betulin suppressed LPS-induced activation by inhibiting inflammatory cytokines.•Molecular docking suggested possible anti-inflammatory mechanism of betulin.•Betulin reduced iNOS expression, prevented JNKs and phosphorylation of NF-κB/p65.
This study aims to investigate active phytochemicals isolated from Pyrola incarnata Fisch. (P. incarnata) and their protection against neuroinflammation induced by LPS. Betulin, accompanied with other 9 compounds, were isolated from P. incarnata and elucidated by spectroscopic analysis (1H-, 13C NMR). ELISA kits and the measurement of NO production based on Griess reaction showed that betulin (5) (250 μg/mL) could suppress LPS-induced activation of microglial cell BV-2 better than others by inhibiting inflammatory cytokines (TNF-α, IL-6, IL-1β) expression and NO production. With the guidance of computer-aided drug design and the analysis of biological experiment, we demonstrated betulin could reduce LPS-induced iNOS expression, prevent JNKs pathways, and down-regulate the phosphorylation levels of NF-κB/p65. In conclusion, betulin isolated from P. incarnata possessed outstanding anti-neuroinflammation potential, presumably related to iNOS expression, JNKs and NF-κB/p65 pathways. Therefore, Pyrola incarnata may be a valuable natural resource and betulin is a potential drug for the treatment of neurodegenerative disorders by inhibiting inflammatory mediators.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>32334913</pmid><doi>10.1016/j.bmcl.2020.127193</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-4473-7122</orcidid><orcidid>https://orcid.org/0000-0002-9797-7429</orcidid></addata></record> |
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| subjects | Animals Betulin Cell Line Dose-Response Relationship, Drug Drug Design Inflammation - drug therapy Inflammation Mediators - chemistry Inflammation Mediators - isolation & purification Inflammation Mediators - pharmacology Lipopolysaccharide Lipopolysaccharides - antagonists & inhibitors Lipopolysaccharides - pharmacology Mice Microglia cells Molecular Conformation Neuroinflammation Nitric Oxide - antagonists & inhibitors Nitric Oxide - biosynthesis Nitric Oxide Synthase Type II - antagonists & inhibitors Nitric Oxide Synthase Type II - metabolism Pyrola - chemistry Pyrola incarnata Stereoisomerism Structure-Activity Relationship Triterpenes - chemistry Triterpenes - isolation & purification Triterpenes - pharmacology |
| title | Betulin isolated from Pyrola incarnata Fisch. inhibited lipopolysaccharide (LPS)-induced neuroinflammation with the guidance of computer-aided drug design |
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