Procyanidin B3 alleviates intervertebral disc degeneration via interaction with the TLR4/MD-2 complex

J Cell Mol Med. 2020 Mar;24(6):3701-3711. doi: 10.1111/jcmm.15074. Epub 2020 Feb 18.

Abstract

As a chronic musculoskeletal degeneration disease, intervertebral disc degeneration (IVDD) has been identified as a crucial cause for low back pain. This condition has a prevalence of 80% among adults without effective preventative therapy. Procyanidin B3 (Pro-B3) is a procyanidin dimer, which is widely present in the human diet and has multiple functions, such as preventing inflammation. But the inhibiting effect of Pro-B3 in IVDD development is still no known. Thus, our study aimed to demonstrate the therapeutical effect of Pro-B3 in IVDD and explain the underlying mechanism. In vitro studies, human nucleus pulposus (NP) cells were isolated and exposed in lipopolysaccharide (LPS) to simulate IVDD development. Pro-B3 pre-treatment inhibited LPS-induced production of inflammation correlated factors such as tumour necrosis factor α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and Nitric oxide (NO). On the other hand, LPS-medicated extracellular matrix (ECM) breakdown was blocked in Pro-B3 treated NP cells. Additionally, Pro-B3 treatment blocked the activation of NF-κB/toll-like receptor 4 pathway in LPS-exposed NP cells. Mechanistically, Pro-B3 could occupy MD-2's hydrophobic pocket exhibiting high affinity for LPS to intervene LPS/TLR4/MD-2 complex formation. In vivo, Pro-B3 treatment prevented the loss of gelatin NP cells and structural damage of annulus fibrosus in rat IVDD model. In brief, Pro-B3 is considered to be a treatment agent for IVDD.

Keywords: Procyanidin B3; intervertebral disc degeneration; nucleus pulposus cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Biflavonoids / chemistry
  • Biflavonoids / pharmacology
  • Biflavonoids / therapeutic use*
  • Catechin / chemistry
  • Catechin / pharmacology
  • Catechin / therapeutic use*
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Disease Progression
  • Extracellular Matrix / metabolism
  • Humans
  • Intervertebral Disc Degeneration / drug therapy*
  • Intervertebral Disc Degeneration / metabolism*
  • Intervertebral Disc Degeneration / pathology
  • Lipopolysaccharides
  • Lymphocyte Antigen 96 / metabolism*
  • Male
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / metabolism
  • Nucleus Pulposus / pathology
  • Proanthocyanidins / chemistry
  • Proanthocyanidins / pharmacology
  • Proanthocyanidins / therapeutic use*
  • Punctures
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • TNF Receptor-Associated Factor 6 / metabolism
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Biflavonoids
  • LY96 protein, human
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Proanthocyanidins
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptor 4
  • procyanidin B3
  • Catechin