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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

Authors :
Zhujun Luo
Hao He
Tiantian Tang
Jun Zhou
Huifang Li
Navindra P. Seeram
Dongli Li
Kun Zhang
Hang Ma
Panpan Wu
Source :
Frontiers in Chemistry, Vol 10 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

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.

Details

Language :
English
ISSN :
22962646
Volume :
10
Database :
Directory of Open Access Journals
Journal :
Frontiers in Chemistry
Publication Type :
Academic Journal
Accession number :
edsdoj.4f6da587c06043669d6c58cb4ab595be
Document Type :
article
Full Text :
https://doi.org/10.3389/fchem.2022.892554