Diterpenoid Compounds Isolated from Chloranthus oldhamii Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway

Chloranthus oldhamii Solms (CO) is a folk medicine for treating infection and arthritis pain but its pharmacological activity and bioactive compounds remain mostly uncharacterized. In this study, the anti-inflammatory compounds of C. oldhamii were identified usi...

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Autores principales:	Lin-Chieh Chiu, Jir-You Wang, Chao-Hsiung Lin, Chung-Hua Hsu, Lie-Chwen Lin, Shu-Ling Fu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	anti-inflammation <i>Chloranthus oldhamii</i> Solms lipopolysaccharide NF-κB decandrin B Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/833c8ee35a1444bd9a5b76e895e6b8c8
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spelling	oai:doaj.org-article:833c8ee35a1444bd9a5b76e895e6b8c82021-11-11T18:31:45ZDiterpenoid Compounds Isolated from <i>Chloranthus oldhamii</i> Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway10.3390/molecules262165401420-3049https://doaj.org/article/833c8ee35a1444bd9a5b76e895e6b8c82021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6540https://doaj.org/toc/1420-3049<i>Chloranthus oldhamii</i> Solms (CO) is a folk medicine for treating infection and arthritis pain but its pharmacological activity and bioactive compounds remain mostly uncharacterized. In this study, the anti-inflammatory compounds of <i>C. oldhamii</i> were identified using an LPS-stimulated, NF-κB-responsive RAW 264.7 macrophage reporter line. Three diterpenoid compounds, 3α-hydroxy-ent-abieta-8,11,13-triene (CO-9), 3α, 7β-dihydroxy-ent-abieta-8,11,13-triene (CO-10), and decandrin B (CO-15) were found to inhibit NF-κB activity at nontoxic concentrations. Moreover, CO-9 and CO-10 suppressed the expression of IL-6 and TNF-α in LPS-stimulated RAW 264.7 cells. The inhibitory effect of CO-9 on TNF-α and IL-6 expression was further demonstrated using LPS-treated bone marrow-derived macrophages. Furthermore, CO-9, CO-10, and CO-15 suppressed LPS-triggered COX-2 expression and downstream PGE2 production in RAW 264.7 cells. CO-9 and CO-10 also reduced LPS-triggered iNOS expression and nitrogen oxide production in RAW 264.7 cells. The anti-inflammatory mechanism of the most effective compound, CO-9, was further investigated. CO-9 attenuated LPS-induced NF-κB activation by reducing the phosphorylation of IKKα/β (Ser176/180), IκBα (Ser32), and p65 (Ser534). Conversely, CO-9 did not affect the LPS-induced activation of MAPK signaling pathways. In summary, this study revealed new anti-inflammatory diterpenoid compounds from C. <i>oldhamii</i> and demonstrated that the IKK-mediated NK-κB pathway is the major target of these compounds.Lin-Chieh ChiuJir-You WangChao-Hsiung LinChung-Hua HsuLie-Chwen LinShu-Ling FuMDPI AGarticleanti-inflammation<i>Chloranthus oldhamii</i> SolmslipopolysaccharideNF-κBdecandrin BOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6540, p 6540 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	anti-inflammation <i>Chloranthus oldhamii</i> Solms lipopolysaccharide NF-κB decandrin B Organic chemistry QD241-441
spellingShingle	anti-inflammation <i>Chloranthus oldhamii</i> Solms lipopolysaccharide NF-κB decandrin B Organic chemistry QD241-441 Lin-Chieh Chiu Jir-You Wang Chao-Hsiung Lin Chung-Hua Hsu Lie-Chwen Lin Shu-Ling Fu Diterpenoid Compounds Isolated from <i>Chloranthus oldhamii</i> Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway
description	<i>Chloranthus oldhamii</i> Solms (CO) is a folk medicine for treating infection and arthritis pain but its pharmacological activity and bioactive compounds remain mostly uncharacterized. In this study, the anti-inflammatory compounds of <i>C. oldhamii</i> were identified using an LPS-stimulated, NF-κB-responsive RAW 264.7 macrophage reporter line. Three diterpenoid compounds, 3α-hydroxy-ent-abieta-8,11,13-triene (CO-9), 3α, 7β-dihydroxy-ent-abieta-8,11,13-triene (CO-10), and decandrin B (CO-15) were found to inhibit NF-κB activity at nontoxic concentrations. Moreover, CO-9 and CO-10 suppressed the expression of IL-6 and TNF-α in LPS-stimulated RAW 264.7 cells. The inhibitory effect of CO-9 on TNF-α and IL-6 expression was further demonstrated using LPS-treated bone marrow-derived macrophages. Furthermore, CO-9, CO-10, and CO-15 suppressed LPS-triggered COX-2 expression and downstream PGE2 production in RAW 264.7 cells. CO-9 and CO-10 also reduced LPS-triggered iNOS expression and nitrogen oxide production in RAW 264.7 cells. The anti-inflammatory mechanism of the most effective compound, CO-9, was further investigated. CO-9 attenuated LPS-induced NF-κB activation by reducing the phosphorylation of IKKα/β (Ser176/180), IκBα (Ser32), and p65 (Ser534). Conversely, CO-9 did not affect the LPS-induced activation of MAPK signaling pathways. In summary, this study revealed new anti-inflammatory diterpenoid compounds from C. <i>oldhamii</i> and demonstrated that the IKK-mediated NK-κB pathway is the major target of these compounds.
format	article
author	Lin-Chieh Chiu Jir-You Wang Chao-Hsiung Lin Chung-Hua Hsu Lie-Chwen Lin Shu-Ling Fu
author_facet	Lin-Chieh Chiu Jir-You Wang Chao-Hsiung Lin Chung-Hua Hsu Lie-Chwen Lin Shu-Ling Fu
author_sort	Lin-Chieh Chiu
title	Diterpenoid Compounds Isolated from <i>Chloranthus oldhamii</i> Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway
title_short	Diterpenoid Compounds Isolated from <i>Chloranthus oldhamii</i> Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway
title_full	Diterpenoid Compounds Isolated from <i>Chloranthus oldhamii</i> Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway
title_fullStr	Diterpenoid Compounds Isolated from <i>Chloranthus oldhamii</i> Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway
title_full_unstemmed	Diterpenoid Compounds Isolated from <i>Chloranthus oldhamii</i> Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway
title_sort	diterpenoid compounds isolated from <i>chloranthus oldhamii</i> solms exert anti-inflammatory effects by inhibiting the ikk/nf-κb pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/833c8ee35a1444bd9a5b76e895e6b8c8
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Diterpenoid Compounds Isolated from <i>Chloranthus oldhamii</i> Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway

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