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Synthesis and Biological Evaluations of Betulinic Acid Derivatives With Inhibitory Activity on Hyaluronidase and Anti-Inflammatory Effects Against Hyaluronic Acid Fragment Induced Inflammation

We previously reported that the structural modifications of pentacyclic triterpenoids including oleanolic acid resulted in enhanced hyaluronidase inhibitory activity but whether this applies to other pentacyclic triterpenoids such as betulinic acid (BA) is unknown. Herein, we synthesized BA derivati...

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Autores principales: Luo, Zhujun, He, Hao, Tang, Tiantian, Zhou, Jun, Li, Huifang, Seeram, Navindra P., Li, Dongli, Zhang, Kun, Ma, Hang, Wu, Panpan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115581/
https://www.ncbi.nlm.nih.gov/pubmed/35601554
http://dx.doi.org/10.3389/fchem.2022.892554
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author Luo, Zhujun
He, Hao
Tang, Tiantian
Zhou, Jun
Li, Huifang
Seeram, Navindra P.
Li, Dongli
Zhang, Kun
Ma, Hang
Wu, Panpan
author_facet Luo, Zhujun
He, Hao
Tang, Tiantian
Zhou, Jun
Li, Huifang
Seeram, Navindra P.
Li, Dongli
Zhang, Kun
Ma, Hang
Wu, Panpan
author_sort Luo, Zhujun
collection PubMed
description We previously reported that the structural modifications of pentacyclic triterpenoids including oleanolic acid resulted in enhanced hyaluronidase inhibitory activity but whether this applies to other pentacyclic triterpenoids such as betulinic acid (BA) is unknown. Herein, we synthesized BA derivatives with an α,β-unsaturated ketene moiety and evaluated for their: 1) hyaluronidase inhibitory activity and, 2) anti-inflammatory effects against lipopolysaccharides (LPS) induced inflammation. Compared to BA, the BA derivatives exerted improved anti-hyaluronidase activity (26.3%–72.8% vs. 22.6%) and anti-inflammatory effects by reducing nitrite production in BV2 cells (3.9%–46.8% vs. 3.4%) and RAW264.7 cells (22.7%–49.2% vs. 20.4%). BA derivatives inhibited LPS-induced production of pro-inflammatory cytokines in THP-1 cells (15.2%–22.4%). BA derivatives also exerted promising anti-inflammatory effects against hyaluronic acid fragment induced nitrite production (8.6%–35.6%) in THP-1 cells. BA derivatives showed augmented anti-hyaluronidase and anti-inflammatory effects but further biological evaluations using in vivo models are warranted to confirm their efficacy.
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spelling pubmed-91155812022-05-19 Synthesis and Biological Evaluations of Betulinic Acid Derivatives With Inhibitory Activity on Hyaluronidase and Anti-Inflammatory Effects Against Hyaluronic Acid Fragment Induced Inflammation Luo, Zhujun He, Hao Tang, Tiantian Zhou, Jun Li, Huifang Seeram, Navindra P. Li, Dongli Zhang, Kun Ma, Hang Wu, Panpan Front Chem Chemistry We previously reported that the structural modifications of pentacyclic triterpenoids including oleanolic acid resulted in enhanced hyaluronidase inhibitory activity but whether this applies to other pentacyclic triterpenoids such as betulinic acid (BA) is unknown. Herein, we synthesized BA derivatives with an α,β-unsaturated ketene moiety and evaluated for their: 1) hyaluronidase inhibitory activity and, 2) anti-inflammatory effects against lipopolysaccharides (LPS) induced inflammation. Compared to BA, the BA derivatives exerted improved anti-hyaluronidase activity (26.3%–72.8% vs. 22.6%) and anti-inflammatory effects by reducing nitrite production in BV2 cells (3.9%–46.8% vs. 3.4%) and RAW264.7 cells (22.7%–49.2% vs. 20.4%). BA derivatives inhibited LPS-induced production of pro-inflammatory cytokines in THP-1 cells (15.2%–22.4%). BA derivatives also exerted promising anti-inflammatory effects against hyaluronic acid fragment induced nitrite production (8.6%–35.6%) in THP-1 cells. BA derivatives showed augmented anti-hyaluronidase and anti-inflammatory effects but further biological evaluations using in vivo models are warranted to confirm their efficacy. Frontiers Media S.A. 2022-05-04 /pmc/articles/PMC9115581/ /pubmed/35601554 http://dx.doi.org/10.3389/fchem.2022.892554 Text en Copyright © 2022 Luo, He, Tang, Zhou, Li, Seeram, Li, Zhang, Ma and Wu. 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 Chemistry
Luo, Zhujun
He, Hao
Tang, Tiantian
Zhou, Jun
Li, Huifang
Seeram, Navindra P.
Li, Dongli
Zhang, Kun
Ma, Hang
Wu, Panpan
Synthesis and Biological Evaluations of Betulinic Acid Derivatives With Inhibitory Activity on Hyaluronidase and Anti-Inflammatory Effects Against Hyaluronic Acid Fragment Induced Inflammation
title Synthesis and Biological Evaluations of Betulinic Acid Derivatives With Inhibitory Activity on Hyaluronidase and Anti-Inflammatory Effects Against Hyaluronic Acid Fragment Induced Inflammation
title_full Synthesis and Biological Evaluations of Betulinic Acid Derivatives With Inhibitory Activity on Hyaluronidase and Anti-Inflammatory Effects Against Hyaluronic Acid Fragment Induced Inflammation
title_fullStr Synthesis and Biological Evaluations of Betulinic Acid Derivatives With Inhibitory Activity on Hyaluronidase and Anti-Inflammatory Effects Against Hyaluronic Acid Fragment Induced Inflammation
title_full_unstemmed Synthesis and Biological Evaluations of Betulinic Acid Derivatives With Inhibitory Activity on Hyaluronidase and Anti-Inflammatory Effects Against Hyaluronic Acid Fragment Induced Inflammation
title_short Synthesis and Biological Evaluations of Betulinic Acid Derivatives With Inhibitory Activity on Hyaluronidase and Anti-Inflammatory Effects Against Hyaluronic Acid Fragment Induced Inflammation
title_sort synthesis and biological evaluations of betulinic acid derivatives with inhibitory activity on hyaluronidase and anti-inflammatory effects against hyaluronic acid fragment induced inflammation
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115581/
https://www.ncbi.nlm.nih.gov/pubmed/35601554
http://dx.doi.org/10.3389/fchem.2022.892554
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