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Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7

Artocarpus tonkinensis (At) leaf decoction, a traditional remedy prepared in North Vietnam by the Hmong ethnic group, is a tea extract rich in bioactive compounds that may have therapeutic effects in arthritis and backache. Indeed, it has been demonstrated that At is able to inhibit Th17 lymphocytes...

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Autores principales: Orecchini, Elena, Mondanelli, Giada, Orabona, Ciriana, Volpi, Claudia, Adorisio, Sabrina, Calvitti, Mario, Thuy, Trinh Thi, Delfino, Domenico V., Belladonna, Maria Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862131/
https://www.ncbi.nlm.nih.gov/pubmed/33551802
http://dx.doi.org/10.3389/fphar.2020.593829
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author Orecchini, Elena
Mondanelli, Giada
Orabona, Ciriana
Volpi, Claudia
Adorisio, Sabrina
Calvitti, Mario
Thuy, Trinh Thi
Delfino, Domenico V.
Belladonna, Maria Laura
author_facet Orecchini, Elena
Mondanelli, Giada
Orabona, Ciriana
Volpi, Claudia
Adorisio, Sabrina
Calvitti, Mario
Thuy, Trinh Thi
Delfino, Domenico V.
Belladonna, Maria Laura
author_sort Orecchini, Elena
collection PubMed
description Artocarpus tonkinensis (At) leaf decoction, a traditional remedy prepared in North Vietnam by the Hmong ethnic group, is a tea extract rich in bioactive compounds that may have therapeutic effects in arthritis and backache. Indeed, it has been demonstrated that At is able to inhibit Th17 lymphocytes development and to protect mice in an experimental model of collagen-induced arthritis. By resorting to macrophage in vitro models of inflammation and osteoclastogenesis, we showed that At extract significantly reduced nitric oxide synthase 2 (NOS2) activity and IL-6 production by RAW 264.7 murine cells. Moreover, At demonstrated an anti-osteoclastogenic effect, as revealed by complete inhibition of TRAP-positive osteoclast formation and decreased expression of key osteoclast-related genes. This At activity likely relies on the inhibition of RANK downstream signaling pathway, as the activation of non-receptor tyrosine kinase Src is reduced upon RANKL-At exposure. Protective effect of At against bone loss was also enlightened in vivo by collagen-induced arthritis (CIA) experiment demonstrating that, although paw edema was only weakly opposed by drinking At decoction, bone and cartilage were well preserved in CIA+At mice and joint tissue expressed decreased levels of osteoclast marker genes respect to CIA control group. Maesopsin 4-O-β-D-glucoside (i.e., TAT-2, one of the main decoction bioactive components) was capable to contrast NOS2 activity, IL-6 expression and osteoclast formation, too, albeit to a lesser extent when compared to At decoction. Overall, this study enlightens another At cell target, macrophages, beside Th17 lymphocytes, and suggests that the anti-arthritic beneficial effects of At decoction largely derives from its ability to counteract not only inflammation, but also osteoclastogenesis.
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spelling pubmed-78621312021-02-06 Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7 Orecchini, Elena Mondanelli, Giada Orabona, Ciriana Volpi, Claudia Adorisio, Sabrina Calvitti, Mario Thuy, Trinh Thi Delfino, Domenico V. Belladonna, Maria Laura Front Pharmacol Pharmacology Artocarpus tonkinensis (At) leaf decoction, a traditional remedy prepared in North Vietnam by the Hmong ethnic group, is a tea extract rich in bioactive compounds that may have therapeutic effects in arthritis and backache. Indeed, it has been demonstrated that At is able to inhibit Th17 lymphocytes development and to protect mice in an experimental model of collagen-induced arthritis. By resorting to macrophage in vitro models of inflammation and osteoclastogenesis, we showed that At extract significantly reduced nitric oxide synthase 2 (NOS2) activity and IL-6 production by RAW 264.7 murine cells. Moreover, At demonstrated an anti-osteoclastogenic effect, as revealed by complete inhibition of TRAP-positive osteoclast formation and decreased expression of key osteoclast-related genes. This At activity likely relies on the inhibition of RANK downstream signaling pathway, as the activation of non-receptor tyrosine kinase Src is reduced upon RANKL-At exposure. Protective effect of At against bone loss was also enlightened in vivo by collagen-induced arthritis (CIA) experiment demonstrating that, although paw edema was only weakly opposed by drinking At decoction, bone and cartilage were well preserved in CIA+At mice and joint tissue expressed decreased levels of osteoclast marker genes respect to CIA control group. Maesopsin 4-O-β-D-glucoside (i.e., TAT-2, one of the main decoction bioactive components) was capable to contrast NOS2 activity, IL-6 expression and osteoclast formation, too, albeit to a lesser extent when compared to At decoction. Overall, this study enlightens another At cell target, macrophages, beside Th17 lymphocytes, and suggests that the anti-arthritic beneficial effects of At decoction largely derives from its ability to counteract not only inflammation, but also osteoclastogenesis. Frontiers Media S.A. 2021-01-22 /pmc/articles/PMC7862131/ /pubmed/33551802 http://dx.doi.org/10.3389/fphar.2020.593829 Text en Copyright © 2021 Belladonna, Orecchini, Mondanelli, Orabona, Volpi, Adorisio, Thuy and Delfino. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Orecchini, Elena
Mondanelli, Giada
Orabona, Ciriana
Volpi, Claudia
Adorisio, Sabrina
Calvitti, Mario
Thuy, Trinh Thi
Delfino, Domenico V.
Belladonna, Maria Laura
Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7
title Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7
title_full Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7
title_fullStr Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7
title_full_unstemmed Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7
title_short Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7
title_sort artocarpus tonkinensis extract inhibits lps-triggered inflammation markers and suppresses rankl-induced osteoclastogenesis in raw264.7
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862131/
https://www.ncbi.nlm.nih.gov/pubmed/33551802
http://dx.doi.org/10.3389/fphar.2020.593829
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