Anti-Inflammatory Effects of Formononetin 7- O-phosphate, a Novel Biorenovation Product, on LPS-Stimulated RAW 264.7 Macrophage Cells

Molecules. 2019 Oct 30;24(21):3910. doi: 10.3390/molecules24213910.

Abstract

Biorenovation is a microbial enzyme-catalyzed structural modification of organic compounds with the potential benefits of reduced toxicity and improved biological properties relative to their precursor compounds. In this study, we synthesized a novel compound verified as formononetin 7-O-phosphate (FMP) from formononetin (FM) using microbial biotransformation. We further compared the anti-inflammatory properties of FMP to FM in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells. We observed that cell viabilities and inhibitory effects on LPS-induced nitric oxide (NO) production were greater in FMP-treated RAW 264.7 cells than in their FM-treated counterparts. In addition, FMP treatment suppressed the production of proinflammatory cytokines such as prostaglandin-E2 (PGE2), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in a dose-dependent manner and concomitantly decreased the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). We also found that FMP exerted its anti-inflammatory effects through the downregulation of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa B (NF-κB) signaling pathways. In conclusion, we generated a novel anti-inflammatory compound using biorenovation and demonstrated its efficacy in cell-based in vitro assays.

Keywords: MAPK pathway; NF-κB pathway; anti-inflammatory; biorenovation; formononetin 7-O-phosphate.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Dinoprostone / metabolism
  • Inflammation Mediators / metabolism
  • Isoflavones / chemistry
  • Isoflavones / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • MAP Kinase Signaling System
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • RAW 264.7 Cells
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Isoflavones
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • formononetin
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Dinoprostone