Open AccessProcyanidin B3 alleviates intervertebral disc degeneration via interaction with the TLR4/MD‐2 complex
Author(s) -
Shang Ping,
Tang Qian,
Hu Zhichao,
Huang Shiyuan,
Hu Yuezheng,
Zhu Jianhong,
Liu Haixiao
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15074
Subject(s) - in vivo , inflammation , tlr4 , intervertebral disc , degeneration (medical) , nitric oxide , tumor necrosis factor alpha , in vitro , cancer research , medicine , pharmacology , chemistry , microbiology and biotechnology , biology , biochemistry , pathology , surgery , genetics
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.