# Albiflorin Relieves Intervertebral Disc Degeneration Through Inhibiting Nucleus Pulposus Cell via the p38 MAPK/NF‐κB Pathway

## TL;DR

Albiflorin, a compound from Paeonia lactiflora, may help treat intervertebral disc degeneration by reducing cell death and inflammation through a specific signaling pathway.

## Contribution

This study is the first to demonstrate that albiflorin protects against intervertebral disc degeneration via the p38 MAPK/NF-κB pathway.

## Key findings

- Albiflorin reduced cell death and improved cell survival in nucleus pulposus cells.
- Albiflorin decreased inflammation and extracellular matrix degradation in disc cells.
- Albiflorin's effects were mediated through suppression of the p38 MAPK/NF-κB pathway.

## Abstract

As a chronic musculoskeletal disorder, intervertebral disc degeneration (IDD) is a leading cause of low back pain. Inflammatory response plays a key role in the IDD progression. Albiflorin (AF), a bioactive compound derived from Paeonia lactiflora, exhibits anti‐inflammatory effects in various diseases. However, the effects of AF on IDD remain unexplored. This study explored the protective effect of AF against IDD and elucidate its possible mechanisms.

Nucleus pulposus (NP) cells were stimulated with lipopolysaccharide (LPS
) for 24 h to establish the IDD cell model, followed by AF or p38MAPK agonist (P79350) treatment. Cell viability and apoptosis were evaluated using 5‐ethynyl‐2'‐deoxyuridine (EdU) assay and flow cytometry analysis, respectively. Levels of the Inflammatory cytokines (tumor necrosis factor alpha, TNF‐α; interleukin‐1beta, IL‐1β; IL‐6) were assessed by enzyme‐linked immunosorbent assay (ELISA). The mRNA levels of B‐cell lymphoma‐2 (Bcl‐2), Bcl‐2‐Associated X (Bax), aggrecan, and collagen type II was analyzed by reverse transcriptase‐quantitative polymerase chain reaction (RT‐qPCR), while their protein levels were determined by western blot assay.

LPS induction remarkably inhibited NP cell proliferation (p < 0.001) and induced apoptosis (p < 0.001), which were significantly reversed by AF dose‐dependently. Furthermore, AF treatment dose‐dependently decreased extracellular matrix (ECM) degradation and inflammatory factors secretion in LPS‐induced NP cells, evidenced by enhanced aggrecan and collagen type II protein expression (all p < 0.01), and reduced TNF‐α, IL‐1β, and IL‐6 section (all p < 0.05). Mechanistically, AF exerted its protective effects by suppressing the p38 mitogen‐activated protein kinase (MAPK)/nuclear factor κB (NF‐κB) signaling pathway, as evidenced by reduced phosphorylation of p38 and p65 (all p < 0.01). Notably, co‐treatment with P79350 partially abolished the protective effects of AF against LPS‐induced NP cell damage.

AF relieved IDD through repressing NP cell apoptosis, inflammatory response, and ECM degradation through the p38 MAPK/NF‐κB pathway, indicating that it is a potential IDD therapeutic agent.