Andrographolide Inhibits Static Mechanical Pressure-Induced Intervertebral Disc Degeneration via the MAPK/Nrf2/HO-1 Pathway

Cunxin Zhang; Ziang Lu; Chaoliang Lyu; Shanshan Zhang; Dechun Wang

doi:10.2147/DDDT.S392535

Andrographolide Inhibits Static Mechanical Pressure-Induced Intervertebral Disc Degeneration via the MAPK/Nrf2/HO-1 Pathway

Drug Des Devel Ther. 2023 Feb 20:17:535-550. doi: 10.2147/DDDT.S392535. eCollection 2023.

Authors

Cunxin Zhang^{1

2}, Ziang Lu³, Chaoliang Lyu², Shanshan Zhang⁴, Dechun Wang¹

Affiliations

¹ Department of Spine Surgery, Qingdao Municipal Hospital, Shandong University, Qingdao, 266061, People's Republic of China.
² Department of Spine Surgery, Jining No.1 People's Hospital, Jining, 272011, People's Republic of China.
³ Jining Medical University, Jining, 272067, People's Republic of China.
⁴ Department of Neurology, Jining No.1 People's Hospital, Jining, 272011, People's Republic of China.

Abstract

Purpose: To explore the molecular mechanism by which andrographolide (ADR) inhibits static mechanical pressure-induced apoptosis in nucleus pulposus cells (NPCs) and to assess the role of ADR in inhibiting IDD.

Methods: Hematoxylin-eosin (HE), toluidine blue, and immunofluorescence staining were used to identify NPCs. An NPC apoptosis model was constructed using a homemade cell pressurization device. The proliferation activity, reactive oxygen species (ROS) content, and apoptosis rate were detected using kits. The expression of related proteins was detected using Western blot. A rat tailbone IDD model was constructed using a homemade tailbone stress device. HE staining and safranine O-fast green FCF cartilage staining were used to observe the degeneration degree of the intervertebral disk.

Results: ADR inhibits static mechanical pressure-induced apoptosis and ROS accumulation in NPCs and improves cell viability. ADR can promote the expression of Heme oxygenase-1 (HO-1), p-Nrf2, p-p38, p-Erk1/2, p-JNK, and other proteins, and its effects can be blocked by inhibitors of the above proteins.

Conclusion: ADR can inhibit IDD by activating the MAPK/Nrf2/HO-1 signaling pathway and suppressing static mechanical pressure-induced ROS accumulation in the NPCs.

Keywords: HO-1; andrographolide; apoptosis; intervertebral disc degeneration; nucleus pulposus cells; reactive oxygen species.

MeSH terms

Animals
Apoptosis
Intervertebral Disc Degeneration* / drug therapy
Intervertebral Disc Degeneration* / metabolism
MAP Kinase Signaling System
NF-E2-Related Factor 2 / metabolism
Rats
Reactive Oxygen Species / metabolism
Signal Transduction

Substances

andrographolide
NF-E2-Related Factor 2
Reactive Oxygen Species
Hmox1 protein, rat

Grants and funding

This research was funded by Jining City Key Research and Development Program Project, grant number 2020JKNS008, and Shandong Province Medical and Health Science and Technology Development Plan Project, grant number 202104070383.