Neferine, a Bisbenzylisoquinoline Alkaloid, Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis

Am J Chin Med. 2018;46(6):1263-1279. doi: 10.1142/S0192415X18500660. Epub 2018 Aug 27.

Abstract

Both the incidence and prevalence of ulcerative colitis (UC) are increasing throughout the world. Neferine, a natural alkaloid, demonstrated a variety of biological activities. In this study, the anti-inflammatory effect of neferine was investigated. Raw264.7 cells were stimulated with lipopolysaccharide (LPS) or LPS plus Z-VAD-fmk (Z-VAD). The inhibitory effect of neferine on secretion of nitrite, cytokines tumor necrosis factor alpha (TNF-[Formula: see text]) and interleukin 6 (IL-6), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined. The protective effect of neferine was investigated in dextran sulfate sodium (DSS)-induced UC mouse model. Neferine significantly inhibited LPS and LPS plus Z-VAD induced secretion of nitrite, cytokines, and expression of iNOS and COX-2. Oral administration of neferine (10[Formula: see text]mg/kg and 25[Formula: see text]mg/kg) significantly reduced DSS-induced mouse weight loss, decreased disease activity index (DAI) scores, improved colon pathological changes, and decreased plasma cytokines. In addition, neferine significantly inhibited the protein expression of iNOS, COX-2, receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL), and increased the protein expression of caspase-8 in colon tissues. These data suggest that neferine was a potent anti-inflammatory agent against LPS and DSS induced inflammation both in vitro and in vivo.

Keywords: Inflammation; Neferine; Ulcerative Colitis.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents*
  • Benzylisoquinolines / administration & dosage*
  • Benzylisoquinolines / isolation & purification
  • Benzylisoquinolines / pharmacology*
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / metabolism*
  • Colon / metabolism
  • Cyclooxygenase 2 / metabolism
  • Dextran Sulfate / adverse effects*
  • Disease Models, Animal
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nelumbo / chemistry
  • Nitric Oxide Synthase Type II / metabolism
  • Nitrites / metabolism
  • Phytotherapy*
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Benzylisoquinolines
  • Interleukin-6
  • Nitrites
  • Tumor Necrosis Factor-alpha
  • neferine
  • Dextran Sulfate
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2