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Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells

Artocarpus lakoocha 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 underly...

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Autores principales: Hankittichai, Phateep, Buacheen, Pensiri, Pitchakarn, Pornsiri, Na Takuathung, Mingkwan, Wikan, Nitwara, Smith, Duncan R., Potikanond, Saranyapin, Nimlamool, Wutigri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072914/
https://www.ncbi.nlm.nih.gov/pubmed/32079307
http://dx.doi.org/10.3390/ijms21041355
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author Hankittichai, Phateep
Buacheen, Pensiri
Pitchakarn, Pornsiri
Na Takuathung, Mingkwan
Wikan, Nitwara
Smith, Duncan R.
Potikanond, Saranyapin
Nimlamool, Wutigri
author_facet Hankittichai, Phateep
Buacheen, Pensiri
Pitchakarn, Pornsiri
Na Takuathung, Mingkwan
Wikan, Nitwara
Smith, Duncan R.
Potikanond, Saranyapin
Nimlamool, Wutigri
author_sort Hankittichai, Phateep
collection PubMed
description Artocarpus lakoocha 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.
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spelling pubmed-70729142020-03-19 Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells Hankittichai, Phateep Buacheen, Pensiri Pitchakarn, Pornsiri Na Takuathung, Mingkwan Wikan, Nitwara Smith, Duncan R. Potikanond, Saranyapin Nimlamool, Wutigri Int J Mol Sci Article Artocarpus lakoocha 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. MDPI 2020-02-17 /pmc/articles/PMC7072914/ /pubmed/32079307 http://dx.doi.org/10.3390/ijms21041355 Text en © 2020 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hankittichai, Phateep
Buacheen, Pensiri
Pitchakarn, Pornsiri
Na Takuathung, Mingkwan
Wikan, Nitwara
Smith, Duncan R.
Potikanond, Saranyapin
Nimlamool, Wutigri
Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells
title Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells
title_full Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells
title_fullStr Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells
title_full_unstemmed Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells
title_short Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells
title_sort artocarpus lakoocha extract inhibits lps-induced inflammatory response in raw 264.7 macrophage cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072914/
https://www.ncbi.nlm.nih.gov/pubmed/32079307
http://dx.doi.org/10.3390/ijms21041355
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