Polysaccharide from Scutellaria baicalensis Georgi ameliorates colitis via suppressing NF-κB signaling and NLRP3 inflammasome activation

Int J Biol Macromol. 2019 Jul 1:132:393-405. doi: 10.1016/j.ijbiomac.2019.03.230. Epub 2019 Mar 30.

Abstract

The purpose of the study was to extract, separate, purify and character Scutellaria baicalensis Georgi polysaccharides, and to further explore the potential mechanism on colitis. Scutellaria baicalensis Georgi was extracted with water and precipitated with alcohol. The obtained crude polysaccharide was fractionated sequentially by DEAE-52 ion exchange column and Sephadex G-100 gel colum. Then, we obtain the purified fraction, named SP1-1. SP1-1 (4.56 × 105 Da) was mainly composed of mannose, ribose, glucuronic acid, glucose, xylose and arabinose with molar ratios of 2.14:3.61:1:2.86:5.98:36.39. FI-TR indicated SP1-1 had the characteristic absorption of polysaccharides with a pyranoid ring. SEM displayed honeycomb structure. Oral administration of SP1-1 significantly decreased disease activity index, ameliorated dextran sulfate sodium-induced colonic pathological damage, and reduced myeloperoxidase activity. Additionally, SP1-1 markedly suppressed the proinflammatory cytokines level, including IL-1β, IL-18 and TNF-α, in the serum and colon of DSS-induced mice and THP-1-derived macrophages. Furthermore, a decreased CD11b+ macrophage infiltration in colons and inactivation of caspase-1 in peritoneal macrophages were detected in SP1-1-treated mice. The mechanisms responsible for these effects of SP1-1 were attributed to its inhibition on NF-κB signaling and NLRP3 inflammasome activation. These findings support SP1-1 as a novel drug candidate in the treatment of colitis.

Keywords: Colitis; NF-κB; NLRP3 inflammasome; Polysaccharide.

MeSH terms

  • Animals
  • Caspase 1 / metabolism
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / pathology*
  • Cytokines / biosynthesis
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Inflammasomes / metabolism
  • Macrophages / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Weight
  • NF-kappa B / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacology*
  • Polysaccharides / therapeutic use
  • Scutellaria baicalensis / chemistry*
  • Signal Transduction / drug effects*

Substances

  • Cytokines
  • Inflammasomes
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Polysaccharides
  • Caspase 1