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Molecules (Basel, Switzerland)
Jun 18, 2022;27 (12):

Anti-Inflammatory Activity of Oxyresveratrol Tetraacetate, an Ester Prodrug of Oxyresveratrol, on Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells.

Wuttinont Thaweesest, Visarut Buranasudja, Rianthong Phumsuay, Chawanphat Muangnoi, Opa Vajragupta, Boonchoo Sritularak, Paitoon Rashatasakhon, Pornchai Rojsitthisak
Author Information
  1. Wuttinont Thaweesest: Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand.
  2. Visarut Buranasudja: Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand. ORCID
  3. Rianthong Phumsuay: Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand.
  4. Chawanphat Muangnoi: Cell and Animal Model Unit, Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand. ORCID
  5. Opa Vajragupta: Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand. ORCID
  6. Boonchoo Sritularak: Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand. ORCID
  7. Paitoon Rashatasakhon: Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  8. Pornchai Rojsitthisak: Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand. ORCID
PMID: 35745046 DOI: 10.3390/molecules27123922

Abstract

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.

Keywords

COX-2 Caco-2 MAPKs iNOS oxyresveratrol permeation

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Grants

  1. GCE 6503433003-1/Chulalongkorn University
  2. The Celebrations on the Auspicious Occasion of Her Royal Highness Princess Maha Chakri Sirindhorn's 5th Cycle (60th) Birthday/Chulongkorn University

MeSH Term

Animals
Anti-Inflammatory Agents
Caco-2 Cells
Cyclooxygenase 2
Esters
Humans
Inflammation
Lipopolysaccharides
Macrophages
Mice
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase Type II
Plant Extracts
Prodrugs
RAW 264.7 Cells
Stilbenes

Chemicals

Anti-Inflammatory Agents
Esters
Lipopolysaccharides
NF-kappa B
Plant Extracts
Prodrugs
Stilbenes
Nitric Oxide
puag-haad
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Journal Article

Word Cloud

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