Cargando…
Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease
Mu Dan Pi (MDP), a traditional Chinese medicine derived from the root bark of Paeonia suffruticosa Andrews, is used to treat autoimmune diseases due to its anti-inflammatory properties. However, the impact of MDP on inflammatory bowel disease (IBD) and its principal active compounds that contribute...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686014/ https://www.ncbi.nlm.nih.gov/pubmed/34938175 http://dx.doi.org/10.3389/fphar.2021.696158 |
_version_ | 1784617934466842624 |
---|---|
author | Wu, Kun-Chang Lee, Der-Yen Hsu, Jeh-Ting Cheng, Chi-Fang Lan, Joung-Liang Chiu, Shao-Chih Cho, Der-Yang Hsu, Jye-Lin |
author_facet | Wu, Kun-Chang Lee, Der-Yen Hsu, Jeh-Ting Cheng, Chi-Fang Lan, Joung-Liang Chiu, Shao-Chih Cho, Der-Yang Hsu, Jye-Lin |
author_sort | Wu, Kun-Chang |
collection | PubMed |
description | Mu Dan Pi (MDP), a traditional Chinese medicine derived from the root bark of Paeonia suffruticosa Andrews, is used to treat autoimmune diseases due to its anti-inflammatory properties. However, the impact of MDP on inflammatory bowel disease (IBD) and its principal active compounds that contribute to the anti-inflammatory properties are uncertain. Thus, this study systemically evaluated the anti-inflammatory effects of fractionated MDP, which has therapeutic potential for IBD. MDP fractions were prepared by multistep fractionation, among which the ethyl acetate-fraction MDP5 exhibited the highest potency, with anti-inflammatory activity screened by the Toll-like receptor (TLR)-2 agonist, Pam3CSK4, in a cell-based model. MDP5 (at 50 μg/ml, p < 0.001) significantly inhibited nuclear factor kappa-B (NF-κB) reporters triggered by Pam3CSK4, without significant cell toxicity. Moreover, MDP5 (at 10 μg/ml) alleviated proinflammatory signaling triggered by Pam3CSK4 in a dose-dependent manner and reduced downstream IL-6 and TNF-α production (p < 0.001) in primary macrophages. MDP5 also mitigated weight loss, clinical inflammation, colonic infiltration of immune cells and cytokine production in a murine colitis model. Index compounds including paeoniflorin derivatives (ranging from 0.1 to 3.4%), gallic acid (1.8%), and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (1.1%) in MDP5 fractions were identified by LC-MS/MS and could be used as anti-inflammatory markers for MDP preparation. Collectively, these data suggest that MDP5 is a promising treatment for IBD patients. |
format | Online Article Text |
id | pubmed-8686014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86860142021-12-21 Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease Wu, Kun-Chang Lee, Der-Yen Hsu, Jeh-Ting Cheng, Chi-Fang Lan, Joung-Liang Chiu, Shao-Chih Cho, Der-Yang Hsu, Jye-Lin Front Pharmacol Pharmacology Mu Dan Pi (MDP), a traditional Chinese medicine derived from the root bark of Paeonia suffruticosa Andrews, is used to treat autoimmune diseases due to its anti-inflammatory properties. However, the impact of MDP on inflammatory bowel disease (IBD) and its principal active compounds that contribute to the anti-inflammatory properties are uncertain. Thus, this study systemically evaluated the anti-inflammatory effects of fractionated MDP, which has therapeutic potential for IBD. MDP fractions were prepared by multistep fractionation, among which the ethyl acetate-fraction MDP5 exhibited the highest potency, with anti-inflammatory activity screened by the Toll-like receptor (TLR)-2 agonist, Pam3CSK4, in a cell-based model. MDP5 (at 50 μg/ml, p < 0.001) significantly inhibited nuclear factor kappa-B (NF-κB) reporters triggered by Pam3CSK4, without significant cell toxicity. Moreover, MDP5 (at 10 μg/ml) alleviated proinflammatory signaling triggered by Pam3CSK4 in a dose-dependent manner and reduced downstream IL-6 and TNF-α production (p < 0.001) in primary macrophages. MDP5 also mitigated weight loss, clinical inflammation, colonic infiltration of immune cells and cytokine production in a murine colitis model. Index compounds including paeoniflorin derivatives (ranging from 0.1 to 3.4%), gallic acid (1.8%), and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (1.1%) in MDP5 fractions were identified by LC-MS/MS and could be used as anti-inflammatory markers for MDP preparation. Collectively, these data suggest that MDP5 is a promising treatment for IBD patients. Frontiers Media S.A. 2021-12-06 /pmc/articles/PMC8686014/ /pubmed/34938175 http://dx.doi.org/10.3389/fphar.2021.696158 Text en Copyright © 2021 Wu, Lee, Hsu, Cheng, Lan, Chiu, Cho and Hsu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). 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 Wu, Kun-Chang Lee, Der-Yen Hsu, Jeh-Ting Cheng, Chi-Fang Lan, Joung-Liang Chiu, Shao-Chih Cho, Der-Yang Hsu, Jye-Lin Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease |
title | Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease |
title_full | Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease |
title_fullStr | Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease |
title_full_unstemmed | Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease |
title_short | Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease |
title_sort | evaluations and mechanistic interrogation of natural products isolated from paeonia suffruticosa for the treatment of inflammatory bowel disease |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686014/ https://www.ncbi.nlm.nih.gov/pubmed/34938175 http://dx.doi.org/10.3389/fphar.2021.696158 |
work_keys_str_mv | AT wukunchang evaluationsandmechanisticinterrogationofnaturalproductsisolatedfrompaeoniasuffruticosaforthetreatmentofinflammatoryboweldisease AT leederyen evaluationsandmechanisticinterrogationofnaturalproductsisolatedfrompaeoniasuffruticosaforthetreatmentofinflammatoryboweldisease AT hsujehting evaluationsandmechanisticinterrogationofnaturalproductsisolatedfrompaeoniasuffruticosaforthetreatmentofinflammatoryboweldisease AT chengchifang evaluationsandmechanisticinterrogationofnaturalproductsisolatedfrompaeoniasuffruticosaforthetreatmentofinflammatoryboweldisease AT lanjoungliang evaluationsandmechanisticinterrogationofnaturalproductsisolatedfrompaeoniasuffruticosaforthetreatmentofinflammatoryboweldisease AT chiushaochih evaluationsandmechanisticinterrogationofnaturalproductsisolatedfrompaeoniasuffruticosaforthetreatmentofinflammatoryboweldisease AT choderyang evaluationsandmechanisticinterrogationofnaturalproductsisolatedfrompaeoniasuffruticosaforthetreatmentofinflammatoryboweldisease AT hsujyelin evaluationsandmechanisticinterrogationofnaturalproductsisolatedfrompaeoniasuffruticosaforthetreatmentofinflammatoryboweldisease |