Anti-inflammatory effects of aucubin in cellular and animal models of rheumatoid arthritis.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. It is known that aucubin (AU) exerts anti-inflammatory activity, but its effects and mechanisms in RA are unclear. This study investigated the anti-inflammatory effects and mechanisms of AU in vivo and in vitro. Human fibroblast-like synoviocyte cells from patients with RA (HFLS-RA), RAW264.7 cells, and MC3T3-E1 cells were used to evaluate the effects of AU on migration, invasion, apoptosis, osteoclast differentiation and production. Immunofluorescence was used to observe nuclear translocation of nuclear factor (NF)-κB, the double luciferase reporter gene method was used to observe NF-κB-p65 activity in AU-treated MC3T3-E1 cells. RT-qPCR was used to measure expression of bone metabolism and inflammation-related genes, and western blot was used to measure bone metabolism and NF-κB protein expression levels. Collagen-induced arthritis (CIA) rat model was used for pharmacodynamics study. Arthritis indexes were measured in the ankle and knee, histological staining and Micro-computed tomography were performed on the ankle joints. Also, inflammatory factor gene expression and the levels of NF-κB-related proteins were detected as in vitro. AU effectively inhibited HFLS-RA cell migration and invasion, promoted apoptosis, and inhibited RAW264.7 cell differentiation into osteoclasts, as well as inhibited NF-κB-p65 activity in MC3T3-E1 cells. Notably, AU significantly reduced the gene expression levels of three cell-related inflammatory factors and bone metabolism factors, effectively inhibited the expression of p-Iκκα β, p-IκBα, and p-p65 proteins. In vivo, AU relieved joint inflammation, reduced related inflammatory factors, and inhibited NF-κB signaling. It could be used to treat RA-related synovial inflammation and bone destruction through the NF-κB pathway.

• Authors: Yan Zhang, Li-Dong Tang, Jian-Ying Wang, Hao Wang, Xiao-Yun Chen, Lei Zhang, Ying Yuan
• Journal: Chinese journal of natural medicines (Chin J Nat Med) Vol. 20 Issue 6 Pg. 458-472 (Jun 2022) ISSN: 1875-5364 [Electronic] China
• PMID: 35750385 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Iridoid Glucosides
• NF-kappa B
• aucubin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Arthritis, Experimental
• Arthritis, Rheumatoid (drug therapy)
• Cells, Cultured
• Humans
• Inflammation (drug therapy, pathology)
• Iridoid Glucosides
• NF-kappa B (metabolism)
• Rats
• X-Ray Microtomography