Water-soluble matrine-type alkaloids with potential anti-neuroinflammatory activities from the seeds of Sophora alopecuroides

Bioorg Chem. 2021 Nov:116:105337. doi: 10.1016/j.bioorg.2021.105337. Epub 2021 Sep 11.

Abstract

A phytochemical investigation on the alkaloids from water-soluble part of Sophora alopecuroides led to obtain forty matrine-type alkaloids (1-40) including eighteen new ones (1-18), which covers almost all positions of the oxygen substitution in matrine-type structure. Notably, eight compounds (1-8) belong to rare bis-amide matrine-type alkaloid. The new structures were determined based on extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and six instances, verified by X-ray crystallography. Most of isolates showed anti-neuroinflammatory activities based on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BV2 microglia cells. Especially, compound 39 can suppress those two mediator secretions in a dose-dependent manner with IC50 values of 21.6 ± 0.5 and 16.7 ± 0.8 μM, respectively. Further mechanistic study revealed that 39 suppressed the phosphorylation of IκBα and p65 subunit to regulate the NF-κB signaling pathway.

Keywords: Anti-neuroinflammatory activity; Matrine-type alkaloid; NF-κB signaling pathway; Sophora alopecuroides; Structural modification; Structure-activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / metabolism
  • Matrines
  • Mice
  • Models, Molecular
  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Quinolizines / chemistry
  • Quinolizines / isolation & purification
  • Quinolizines / pharmacology*
  • Seeds / chemistry
  • Signal Transduction / drug effects
  • Solubility
  • Sophora / chemistry*
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism
  • Water / chemistry

Substances

  • Alkaloids
  • Anti-Inflammatory Agents
  • Interleukin-6
  • NF-kappa B
  • Quinolizines
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Water
  • Matrines