Journal of Applied Biological Chemistry

  • Volume 66
  • /
  • Pages.29-38
  • /
  • 2023
  • /
  • 1976-0442(pISSN)
  • /
  • 2234-7941(eISSN)
The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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The Acetylation-based synthesis of 3,3',4',5,5',7-hexaacetate myricetin and evaluation of its anti-inflammatory activities in lipopolysaccharide-induced RAW264.7 mouse macrophage cells

  • Kristina Lama (Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University) ;
  • Hyehyun Hong (Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University) ;
  • Tae-Jin Park (Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University) ;
  • Jin-Soo Park (Natural Product Informatics Research Center, Korea Institute of Science and Technology) ;
  • Won-Jae Chi (Microorganism Resources Division, National Institute of Biological Resources) ;
  • Seung-Young Kim (Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University)
  • Received : 2022.12.14
  • Accepted : 2023.01.19
  • Published : 2023.12.31
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Abstract

Recent studies have highlighted the link between diseases and inflammation across our lifespan. Our sedentary lifestyle, high-calorie diet, chronic stress, chronic infections, and exposure to pollutants and xenobiotics, collectively intensify the course and recurrence of infections and inflammation in our bodies, promoting the prevalence of chronic diseases and aging. Given such phenomena and considering additional factors such as the frequency of prescription, and easy access to over-the-counter drugs, the need for anti-inflammatory therapeutics is ever-increasing. However, the readily available anti-inflammatory treatment option comes with a greater risk of side effects or high cost (biologics). Therefore in this growing competition of discovering and developing new potent anti-inflammatory drugs, we focused on utilizing the established knowledge of traditional medicine to find lead compounds. Since lead optimization is an indispensable step toward drug development, we applied this concept for the production of potent anti-inflammatory compounds achieved by structural modification of flavonoids. The derivative obtained through acetylation of myricetin, 3,3',4',5,5',7-hexaacetate myricetin, showed a greater inhibitory effect in the production of pro-inflammatory mediators such as nitric oxide, Prostaglandin E2, and pro-inflammatory cytokines like interleukin-6, interleukin1β, in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells compared to myricetin. The increased potency of inhibition was in conjunction with an increased inhibitory effect on inducible nitric oxide synthase and cyclooxygenase-2 proteins. Through such measures, this study supports lead optimization for well-established lead compounds from traditional medicine using a simpler and greener chemistry approach for the purpose of designing and developing potent anti-inflammatory therapeutics with possibly fewer side effects and increased bioavailability.

Keywords

Acknowledgement

This research was supported by a grant from the National Institute of Biological Resources (NIBR), funded by the Ministry of Environment (MOE) of the Korea (NIBR202203112). The authors acknowledge the use of VNMRS system belonging to Natural Product Informatics Research Center, Korea Institute of Science and Technology.

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