Anti-Inflammatory Activity of Oxyresveratrol Tetraacetate, an Ester Prodrug of Oxyresveratrol, on Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells.
Animals
Anti-Inflammatory Agents
/ metabolism
Caco-2 Cells
Cyclooxygenase 2
/ metabolism
Esters
/ metabolism
Humans
Inflammation
/ drug therapy
Lipopolysaccharides
/ metabolism
Macrophages
Mice
NF-kappa B
/ metabolism
Nitric Oxide
/ metabolism
Nitric Oxide Synthase Type II
/ metabolism
Plant Extracts
Prodrugs
/ metabolism
RAW 264.7 Cells
Stilbenes
COX-2
Caco-2
MAPKs
iNOS
oxyresveratrol
permeation
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
18 Jun 2022
18 Jun 2022
Historique:
received:
31
05
2022
revised:
15
06
2022
accepted:
16
06
2022
entrez:
24
6
2022
pubmed:
25
6
2022
medline:
28
6
2022
Statut:
epublish
Résumé
Oxyresveratrol (OXY) has been reported for its anti-inflammatory activity; however, the pharmaceutical applications of this compound are limited by its physicochemical properties and poor pharmacokinetic profiles. The use of an ester prodrug is a promising strategy to overcome these obstacles. In previous researches, several carboxylate esters of OXY were synthesized and oxyresveratrol tetraacetate (OXY-TAc) was reported to possess anti-melanogenic and anti-skin-aging properties. In this study, in addition to OXY-TAc, two novel ester prodrugs of OXY, oxyresveratrol tetrapropionate (OXY-TPr), and oxyresveratrol tetrabutyrate (OXY-TBu), were synthesized. Results from the Caco-2-permeation assay suggested that synthesized ester prodrugs can improve the membrane-permeation ability of OXY. The OXY-TAc exhibited the most significant profile, then this prodrug was chosen to observe anti-inflammatory activities with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Our results showed that OXY-Tac significantly alleviated secretion of several pro-inflammatory mediators (nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), mitigated expression of enzyme-regulated inflammation (inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)), and suppressed the MAPK cascades. Interestingly, the observed anti-inflammatory activities of OXY-TAc were more remarkable than those of its parent compound OXY. Taken together, we demonstrated that OXY-TAc improved physicochemical and pharmacokinetic profiles and enhanced the pharmacological effects of OXY. Hence, the results in the present study would strongly support the clinical utilities of OXY-TAc for the treatment of inflammation-related disorders.
Identifiants
pubmed: 35745046
pii: molecules27123922
doi: 10.3390/molecules27123922
pmc: PMC9228887
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Esters
0
Lipopolysaccharides
0
NF-kappa B
0
Plant Extracts
0
Prodrugs
0
Stilbenes
0
Nitric Oxide
31C4KY9ESH
puag-haad
4721-07-7
Nitric Oxide Synthase Type II
EC 1.14.13.39
Cyclooxygenase 2
EC 1.14.99.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Chulalongkorn University
ID : GCE 6503433003-1
Organisme : Chulongkorn University
ID : The Celebrations on the Auspicious Occasion of Her Royal Highness Princess Maha Chakri Sirindhorn's 5th Cycle (60th) Birthday
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