Δ8(14)-Ergostenol Glycoside Derivatives Inhibit the Expression of Inflammatory Mediators and Matrix Metalloproteinase

Molecules. 2021 Jul 28;26(15):4547. doi: 10.3390/molecules26154547.

Abstract

Arthritis is a chronic inflammatory disease accompanied by pathological reactions such as swelling, redness, fever, and pain in various joint areas. The drugs currently available to treat arthritis are associated with diverse side-effects. Therefore, there is a need for safer and more effective treatments to alleviate the inflammation of arthritis with fewer side-effects. In this study, a new sterol, Δ8(14)-ergostenol, was discovered, and its glycosides were synthesized and found to be more efficient in terms of synthesis or anti-inflammatory activity than either spinasterol or 5,6-dihydroergosterol is. Among these synthetic glycosides, galactosyl ergostenol inhibited the expression of inflammatory mediators in TNF-α-stimulated FLS and TNF-α-induced MMPs and collagen type II A1 degradation in human chondrocytes. These results suggest the new galactosyl ergostenol as a treatment candidate for arthritis.

Keywords: arthritis; collagen type II A1; ergostenol; ergostenol glycosides; matrix metalloproteinase.

MeSH terms

  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Ergosterol / chemistry
  • Ergosterol / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Glycosides / chemical synthesis
  • Glycosides / pharmacology*
  • Humans
  • Inflammation / prevention & control
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Models, Biological
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Signal Transduction
  • Synoviocytes / cytology
  • Synoviocytes / drug effects*
  • Synoviocytes / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Anti-Inflammatory Agents
  • COL2A1 protein, human
  • CXCL8 protein, human
  • Collagen Type II
  • Glycosides
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Matrix Metalloproteinases
  • Ergosterol