From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution

Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as e...
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Autor*in:	Tran Thi Van Anh [verfasserIn] Alilou Mostafa [verfasserIn] Zhigang Rao [verfasserIn] Simona Pace [verfasserIn] Stefan Schwaiger [verfasserIn] Christian Kretzer [verfasserIn] Veronika Temml [verfasserIn] Carsten Giesel [verfasserIn] Paul M. Jordan [verfasserIn] Rossella Bilancia [verfasserIn] Christina Weinigel [verfasserIn] Silke Rummler [verfasserIn] Birgit Waltenberger [verfasserIn] Tran Hung [verfasserIn] Antonietta Rossi [verfasserIn] Hermann Stuppner [verfasserIn] Oliver Werz [verfasserIn] Andreas Koeberle [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Lipoxygenase Inflammation Resolution Natural product Lipidomics Lipid mediator

Übergeordnetes Werk:	In: Acta Pharmaceutica Sinica B - Elsevier, 2013, 11(2021), 6, Seite 1629-1647
Übergeordnetes Werk:	volume:11 ; year:2021 ; number:6 ; pages:1629-1647

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.apsb.2021.04.011

Katalog-ID:	DOAJ05294297X

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allfields	10.1016/j.apsb.2021.04.011 doi (DE-627)DOAJ05294297X (DE-599)DOAJa137a9aac80f4a9797946a4d4cfeaf30 DE-627 ger DE-627 rakwb eng RM1-950 Tran Thi Van Anh verfasserin aut From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4′-ol from Dracaena cambodiana, which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators (SPM). Elucidation of the absolute configurations of 8-methylsocotrin-4′-ol revealed the 2S,γS-isomer being most active, and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase subdomains. We identified additional subordinate targets within lipid mediator biosynthesis, including microsomal prostaglandin E2 synthase-1. Leukotriene production is efficiently suppressed in activated human neutrophils, macrophages, and blood, while the induction of SPM biosynthesis is restricted to M2 macrophages. The shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell infiltration. In summary, we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles. Lipoxygenase Inflammation Resolution Natural product Lipidomics Lipid mediator Therapeutics. Pharmacology Alilou Mostafa verfasserin aut Zhigang Rao verfasserin aut Simona Pace verfasserin aut Stefan Schwaiger verfasserin aut Christian Kretzer verfasserin aut Veronika Temml verfasserin aut Carsten Giesel verfasserin aut Paul M. Jordan verfasserin aut Rossella Bilancia verfasserin aut Christina Weinigel verfasserin aut Silke Rummler verfasserin aut Birgit Waltenberger verfasserin aut Tran Hung verfasserin aut Antonietta Rossi verfasserin aut Hermann Stuppner verfasserin aut Oliver Werz verfasserin aut Andreas Koeberle verfasserin aut In Acta Pharmaceutica Sinica B Elsevier, 2013 11(2021), 6, Seite 1629-1647 (DE-627)670211095 (DE-600)2631779-5 22113843 nnns volume:11 year:2021 number:6 pages:1629-1647 https://doi.org/10.1016/j.apsb.2021.04.011 kostenfrei https://doaj.org/article/a137a9aac80f4a9797946a4d4cfeaf30 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211383521001386 kostenfrei https://doaj.org/toc/2211-3835 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 6 1629-1647
spelling	10.1016/j.apsb.2021.04.011 doi (DE-627)DOAJ05294297X (DE-599)DOAJa137a9aac80f4a9797946a4d4cfeaf30 DE-627 ger DE-627 rakwb eng RM1-950 Tran Thi Van Anh verfasserin aut From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4′-ol from Dracaena cambodiana, which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators (SPM). Elucidation of the absolute configurations of 8-methylsocotrin-4′-ol revealed the 2S,γS-isomer being most active, and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase subdomains. We identified additional subordinate targets within lipid mediator biosynthesis, including microsomal prostaglandin E2 synthase-1. Leukotriene production is efficiently suppressed in activated human neutrophils, macrophages, and blood, while the induction of SPM biosynthesis is restricted to M2 macrophages. The shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell infiltration. In summary, we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles. Lipoxygenase Inflammation Resolution Natural product Lipidomics Lipid mediator Therapeutics. Pharmacology Alilou Mostafa verfasserin aut Zhigang Rao verfasserin aut Simona Pace verfasserin aut Stefan Schwaiger verfasserin aut Christian Kretzer verfasserin aut Veronika Temml verfasserin aut Carsten Giesel verfasserin aut Paul M. Jordan verfasserin aut Rossella Bilancia verfasserin aut Christina Weinigel verfasserin aut Silke Rummler verfasserin aut Birgit Waltenberger verfasserin aut Tran Hung verfasserin aut Antonietta Rossi verfasserin aut Hermann Stuppner verfasserin aut Oliver Werz verfasserin aut Andreas Koeberle verfasserin aut In Acta Pharmaceutica Sinica B Elsevier, 2013 11(2021), 6, Seite 1629-1647 (DE-627)670211095 (DE-600)2631779-5 22113843 nnns volume:11 year:2021 number:6 pages:1629-1647 https://doi.org/10.1016/j.apsb.2021.04.011 kostenfrei https://doaj.org/article/a137a9aac80f4a9797946a4d4cfeaf30 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211383521001386 kostenfrei https://doaj.org/toc/2211-3835 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 6 1629-1647
allfields_unstemmed	10.1016/j.apsb.2021.04.011 doi (DE-627)DOAJ05294297X (DE-599)DOAJa137a9aac80f4a9797946a4d4cfeaf30 DE-627 ger DE-627 rakwb eng RM1-950 Tran Thi Van Anh verfasserin aut From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4′-ol from Dracaena cambodiana, which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators (SPM). Elucidation of the absolute configurations of 8-methylsocotrin-4′-ol revealed the 2S,γS-isomer being most active, and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase subdomains. We identified additional subordinate targets within lipid mediator biosynthesis, including microsomal prostaglandin E2 synthase-1. Leukotriene production is efficiently suppressed in activated human neutrophils, macrophages, and blood, while the induction of SPM biosynthesis is restricted to M2 macrophages. The shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell infiltration. In summary, we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles. Lipoxygenase Inflammation Resolution Natural product Lipidomics Lipid mediator Therapeutics. Pharmacology Alilou Mostafa verfasserin aut Zhigang Rao verfasserin aut Simona Pace verfasserin aut Stefan Schwaiger verfasserin aut Christian Kretzer verfasserin aut Veronika Temml verfasserin aut Carsten Giesel verfasserin aut Paul M. Jordan verfasserin aut Rossella Bilancia verfasserin aut Christina Weinigel verfasserin aut Silke Rummler verfasserin aut Birgit Waltenberger verfasserin aut Tran Hung verfasserin aut Antonietta Rossi verfasserin aut Hermann Stuppner verfasserin aut Oliver Werz verfasserin aut Andreas Koeberle verfasserin aut In Acta Pharmaceutica Sinica B Elsevier, 2013 11(2021), 6, Seite 1629-1647 (DE-627)670211095 (DE-600)2631779-5 22113843 nnns volume:11 year:2021 number:6 pages:1629-1647 https://doi.org/10.1016/j.apsb.2021.04.011 kostenfrei https://doaj.org/article/a137a9aac80f4a9797946a4d4cfeaf30 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211383521001386 kostenfrei https://doaj.org/toc/2211-3835 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 6 1629-1647
allfieldsGer	10.1016/j.apsb.2021.04.011 doi (DE-627)DOAJ05294297X (DE-599)DOAJa137a9aac80f4a9797946a4d4cfeaf30 DE-627 ger DE-627 rakwb eng RM1-950 Tran Thi Van Anh verfasserin aut From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4′-ol from Dracaena cambodiana, which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators (SPM). Elucidation of the absolute configurations of 8-methylsocotrin-4′-ol revealed the 2S,γS-isomer being most active, and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase subdomains. We identified additional subordinate targets within lipid mediator biosynthesis, including microsomal prostaglandin E2 synthase-1. Leukotriene production is efficiently suppressed in activated human neutrophils, macrophages, and blood, while the induction of SPM biosynthesis is restricted to M2 macrophages. The shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell infiltration. In summary, we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles. Lipoxygenase Inflammation Resolution Natural product Lipidomics Lipid mediator Therapeutics. Pharmacology Alilou Mostafa verfasserin aut Zhigang Rao verfasserin aut Simona Pace verfasserin aut Stefan Schwaiger verfasserin aut Christian Kretzer verfasserin aut Veronika Temml verfasserin aut Carsten Giesel verfasserin aut Paul M. Jordan verfasserin aut Rossella Bilancia verfasserin aut Christina Weinigel verfasserin aut Silke Rummler verfasserin aut Birgit Waltenberger verfasserin aut Tran Hung verfasserin aut Antonietta Rossi verfasserin aut Hermann Stuppner verfasserin aut Oliver Werz verfasserin aut Andreas Koeberle verfasserin aut In Acta Pharmaceutica Sinica B Elsevier, 2013 11(2021), 6, Seite 1629-1647 (DE-627)670211095 (DE-600)2631779-5 22113843 nnns volume:11 year:2021 number:6 pages:1629-1647 https://doi.org/10.1016/j.apsb.2021.04.011 kostenfrei https://doaj.org/article/a137a9aac80f4a9797946a4d4cfeaf30 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211383521001386 kostenfrei https://doaj.org/toc/2211-3835 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 6 1629-1647
allfieldsSound	10.1016/j.apsb.2021.04.011 doi (DE-627)DOAJ05294297X (DE-599)DOAJa137a9aac80f4a9797946a4d4cfeaf30 DE-627 ger DE-627 rakwb eng RM1-950 Tran Thi Van Anh verfasserin aut From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4′-ol from Dracaena cambodiana, which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators (SPM). Elucidation of the absolute configurations of 8-methylsocotrin-4′-ol revealed the 2S,γS-isomer being most active, and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase subdomains. We identified additional subordinate targets within lipid mediator biosynthesis, including microsomal prostaglandin E2 synthase-1. Leukotriene production is efficiently suppressed in activated human neutrophils, macrophages, and blood, while the induction of SPM biosynthesis is restricted to M2 macrophages. The shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell infiltration. In summary, we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles. Lipoxygenase Inflammation Resolution Natural product Lipidomics Lipid mediator Therapeutics. Pharmacology Alilou Mostafa verfasserin aut Zhigang Rao verfasserin aut Simona Pace verfasserin aut Stefan Schwaiger verfasserin aut Christian Kretzer verfasserin aut Veronika Temml verfasserin aut Carsten Giesel verfasserin aut Paul M. Jordan verfasserin aut Rossella Bilancia verfasserin aut Christina Weinigel verfasserin aut Silke Rummler verfasserin aut Birgit Waltenberger verfasserin aut Tran Hung verfasserin aut Antonietta Rossi verfasserin aut Hermann Stuppner verfasserin aut Oliver Werz verfasserin aut Andreas Koeberle verfasserin aut In Acta Pharmaceutica Sinica B Elsevier, 2013 11(2021), 6, Seite 1629-1647 (DE-627)670211095 (DE-600)2631779-5 22113843 nnns volume:11 year:2021 number:6 pages:1629-1647 https://doi.org/10.1016/j.apsb.2021.04.011 kostenfrei https://doaj.org/article/a137a9aac80f4a9797946a4d4cfeaf30 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211383521001386 kostenfrei https://doaj.org/toc/2211-3835 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 6 1629-1647
language	English
source	In Acta Pharmaceutica Sinica B 11(2021), 6, Seite 1629-1647 volume:11 year:2021 number:6 pages:1629-1647
sourceStr	In Acta Pharmaceutica Sinica B 11(2021), 6, Seite 1629-1647 volume:11 year:2021 number:6 pages:1629-1647
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Lipoxygenase Inflammation Resolution Natural product Lipidomics Lipid mediator Therapeutics. Pharmacology
isfreeaccess_bool	true
container_title	Acta Pharmaceutica Sinica B
authorswithroles_txt_mv	Tran Thi Van Anh @@aut@@ Alilou Mostafa @@aut@@ Zhigang Rao @@aut@@ Simona Pace @@aut@@ Stefan Schwaiger @@aut@@ Christian Kretzer @@aut@@ Veronika Temml @@aut@@ Carsten Giesel @@aut@@ Paul M. Jordan @@aut@@ Rossella Bilancia @@aut@@ Christina Weinigel @@aut@@ Silke Rummler @@aut@@ Birgit Waltenberger @@aut@@ Tran Hung @@aut@@ Antonietta Rossi @@aut@@ Hermann Stuppner @@aut@@ Oliver Werz @@aut@@ Andreas Koeberle @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	670211095
id	DOAJ05294297X
language_de	englisch
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callnumber-first	R - Medicine
author	Tran Thi Van Anh
spellingShingle	Tran Thi Van Anh misc RM1-950 misc Lipoxygenase misc Inflammation misc Resolution misc Natural product misc Lipidomics misc Lipid mediator misc Therapeutics. Pharmacology From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution
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topic_title	RM1-950 From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution Lipoxygenase Inflammation Resolution Natural product Lipidomics Lipid mediator
topic	misc RM1-950 misc Lipoxygenase misc Inflammation misc Resolution misc Natural product misc Lipidomics misc Lipid mediator misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc Lipoxygenase misc Inflammation misc Resolution misc Natural product misc Lipidomics misc Lipid mediator misc Therapeutics. Pharmacology
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title	From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution
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title_full	From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution
author_sort	Tran Thi Van Anh
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author_browse	Tran Thi Van Anh Alilou Mostafa Zhigang Rao Simona Pace Stefan Schwaiger Christian Kretzer Veronika Temml Carsten Giesel Paul M. Jordan Rossella Bilancia Christina Weinigel Silke Rummler Birgit Waltenberger Tran Hung Antonietta Rossi Hermann Stuppner Oliver Werz Andreas Koeberle
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doi_str_mv	10.1016/j.apsb.2021.04.011
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title_sort	from vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution
callnumber	RM1-950
title_auth	From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution
abstract	Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4′-ol from Dracaena cambodiana, which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators (SPM). Elucidation of the absolute configurations of 8-methylsocotrin-4′-ol revealed the 2S,γS-isomer being most active, and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase subdomains. We identified additional subordinate targets within lipid mediator biosynthesis, including microsomal prostaglandin E2 synthase-1. Leukotriene production is efficiently suppressed in activated human neutrophils, macrophages, and blood, while the induction of SPM biosynthesis is restricted to M2 macrophages. The shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell infiltration. In summary, we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles.
abstractGer	Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4′-ol from Dracaena cambodiana, which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators (SPM). Elucidation of the absolute configurations of 8-methylsocotrin-4′-ol revealed the 2S,γS-isomer being most active, and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase subdomains. We identified additional subordinate targets within lipid mediator biosynthesis, including microsomal prostaglandin E2 synthase-1. Leukotriene production is efficiently suppressed in activated human neutrophils, macrophages, and blood, while the induction of SPM biosynthesis is restricted to M2 macrophages. The shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell infiltration. In summary, we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles.
abstract_unstemmed	Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4′-ol from Dracaena cambodiana, which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators (SPM). Elucidation of the absolute configurations of 8-methylsocotrin-4′-ol revealed the 2S,γS-isomer being most active, and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase subdomains. We identified additional subordinate targets within lipid mediator biosynthesis, including microsomal prostaglandin E2 synthase-1. Leukotriene production is efficiently suppressed in activated human neutrophils, macrophages, and blood, while the induction of SPM biosynthesis is restricted to M2 macrophages. The shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell infiltration. In summary, we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles.
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title_short	From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution
url	https://doi.org/10.1016/j.apsb.2021.04.011 https://doaj.org/article/a137a9aac80f4a9797946a4d4cfeaf30 http://www.sciencedirect.com/science/article/pii/S2211383521001386 https://doaj.org/toc/2211-3835
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author2	Alilou Mostafa Zhigang Rao Simona Pace Stefan Schwaiger Christian Kretzer Veronika Temml Carsten Giesel Paul M. Jordan Rossella Bilancia Christina Weinigel Silke Rummler Birgit Waltenberger Tran Hung Antonietta Rossi Hermann Stuppner Oliver Werz Andreas Koeberle
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up_date	2024-07-03T14:55:26.801Z
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From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution

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