Rosmanol and Carnosol Synergistically Alleviate Rheumatoid Arthritis through Inhibiting TLR4/NF-κB/MAPK Pathway.

Lianchun Li,Desheng Ning,Zhenghong Pan,Yuxia Fu

doi:10.3390/molecules27010078

Lianchun Li, Desheng Ning + Show 2 more

Open Access

https://doi.org/10.3390/molecules27010078

Copy DOI

Abstract

Callicarpalongissima has been used as a Yao folk medicine to treat arthritis for years in China, although its active anti-arthritic moieties have not been clarified so far. In this study, two natural phenolic diterpenoids with anti-rheumatoid arthritis (RA) effects, rosmanol and carnosol, isolated from the medicinal plant were reported on for the first time. In type II collagen-induced arthritis DBA/1 mice, both rosmanol (40 mg/kg/d) and carnosol (40 mg/kg/d) alone alleviated the RA symptoms, such as swelling, redness, and synovitis; decreased the arthritis index score; and downregulated the serum pro-inflammatory cytokine levels of interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor α (TNF-α). Additionally, they blocked the activation of the Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways. Of particular interest was that when they were used in combination (20 mg/kg/d each), the anti-RA effect and inhibitory activity on the TLR4/NF-κB/MAPK pathway were significantly enhanced. The results demonstrated that rosmanol and carnosol synergistically alleviated RA by inhibiting inflammation through regulating the TLR4/NF-κB/MAPK pathway, meaning they have the potential to be developed into novel, safe natural combinations for the treatment of RA.

Highlights

Academic Editors: Raffaele PezzaniRheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by the presence of autoantibodies, lasting synovitis, and systemic inflammation
The arthritis severity was alleviated in mice treated by rosmanol, carnosol, or the combination of both (Figure 2d–f)
On day 42, the arthritis severity was markedly attenuated in the rosmanol-treated and carnosol-treated group compared to the model group (p < 0.05), with arthritis index scores of 8.7, 8.5, and 10.0, respectively

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by the presence of autoantibodies, lasting synovitis, and systemic inflammation. It can cause joint destruction and disability with a prevalence of 0.5–1%, leading to considerable costs to both the individual and the community [1]. Nonsteroidal anti-inflammation drugs, glucocorticoids, disease-modifying anti-rheumatic drugs, and biological agents are the currently used therapeutic drugs for RA. They have different side effects, including gastrointestinal, liver, pulmonary, hematological, neurological, and renal toxicities, as well as risks of serious infections [2]. More antiinflammatory medicinal plants traditionally used to treat RA have been considered, and many medicinal plant-derived anti-RA drugs have been successfully developed, including glucosides of Tripterygium wilfordii and total glucosides of paeony and sinomenine [3,4,5]

Methods

Results

Conclusion