p-Coumaroyl Anthocyanin Mixture Isolated from Tuber Epidermis of Solanum tuberosum Attenuates Reactive Oxygen Species and Pro-inflammatory Mediators by Suppressing NF-κB and STAT1/3 Signaling in LPS-Induced RAW264.7 Macrophages

Biol Pharm Bull. 2017;40(11):1894-1902. doi: 10.1248/bpb.b17-00362.

Abstract

Previously, we first reported the identification of four p-coumaroyl anthocyanins (petanin, peonanin, malvanin, and pelanin) from the tuber epidermis of colored potato (Solanum tuberosum L. cv JAYOUNG). In this study, we investigated the anti-oxidative and anti-inflammatory effects of a mixture of peonanin, malvanin, and pelanin (10 : 3 : 3; CAJY). CAJY displayed considerable radical scavenging capacity of 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), increased mRNA levels of the catalytic and modulatory subunit of glutamate cysteine ligase, and subsequent cellular glutathione content. These increases preceded the inhibition of lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) production. CAJY inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a concentration-dependent manner at the protein, mRNA, and promoter activity levels. These inhibitions caused attendant decreases in the production of prostaglandin E2 (PGE2). CAJY suppressed the production and mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Molecular data revealed that CAJY inhibited the transcriptional activity and translocation of nuclear factor κB (NF-κB) and phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3. Taken together, these results suggest that the anthocyanin mixture exerts anti-inflammatory effects in macrophages, at least in part by reducing ROS production and inactivating NF-κB and STAT 1/3.

Keywords: anthocyanin; anti-inflammatory; antioxidant; macrophage; nuclear factor κB; signal transducer and activator of transcription.

MeSH terms

  • Animals
  • Anthocyanins / chemistry
  • Anthocyanins / pharmacology*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Coumaric Acids
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Dinoprostone / metabolism
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Tubers / chemistry
  • Propionates / chemistry
  • Propionates / pharmacology*
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Solanum tuberosum / chemistry*

Substances

  • Anthocyanins
  • Anti-Inflammatory Agents
  • Coumaric Acids
  • Cytokines
  • Free Radical Scavengers
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Propionates
  • Reactive Oxygen Species
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • p-coumaric acid
  • Dinoprostone