Cardamonin protects nucleus pulposus cells against IL-1β-induced inflammation and catabolism via Nrf2/NF-κB axis.

Abstract

Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain, but effective therapies are still lacking because of its complicated pathology. It has been demonstrated that increased levels of interleukin-1β (IL-1β) may promote the development of IVDD. Cardamonin (CAR) is a chalcone extracted from Alpinia katsumadai and other plants. It exhibits an anti-inflammatory effect in multiple diseases. In the present study, we investigated the protective effects of CAR on rat nucleus pulposus (NP) cells under IL-1β stimulation in vitro and in a puncture-induced rat IVDD model in vivo. We explored the CAR treatment's inhibition of the expression of inflammatory factors such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), nitric oxide (NO), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in rat NP cells. Moreover, the up-regulation of matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) and the degradation of aggrecan and collagen II induced by IL-1β were reversed by CAR. Mechanistically, we demonstrated that CAR inhibited nuclear factor kappa B (NF-κB) signaling by activating the nuclear factor erythroid-derived 2-like 2 (Nrf2) in IL-1β-induced rat NP cells. Furthermore, the protective effect of CAR was shown in the IVDD model through persistent intragastric administration. Taken together, our results revealed that CAR could activate the Nrf2/HO-1 signaling axis and be a novel agent for IVDD therapy.

• Authors: Chenglong Xie , Haiwei Ma , Yifeng Shi , Junli Li , Hongqiang Wu , Ben Wang , Zhenxuan Shao , Chongan Huang , Jiaoxiang Chen , Liaojun Sun , Yifei Zhou , Naifeng Tian , Yaosen Wu , Weiyang Gao , Aimin Wu , Xiangyang Wang , Xiaolei Zhang
• Journal: Food & function (Food Funct) Vol. 12 Issue 6 Pg. 2703-2714 (Mar 21 2021) ISSN: 2042-650X [Electronic] England
• PMID: 33666626 (Publication Type: Journal Article)

Chemical References

• Chalcones
• Interleukin-1beta
• NF-E2-Related Factor 2
• NF-kappa B
• cardamonin

Topics

• Animals
• Cell Survival (drug effects)
• Cells, Cultured
• Chalcones (pharmacology)
• Inflammation (metabolism)
• Interleukin-1beta (metabolism)
• Male
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Nucleus Pulposus (cytology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)