Abstract
Periploca forrestii Schltr. (P. forrestii) is a species used in Traditional Chinese Medicine (TCM) known as “Miao medicine”, and has a long history of use in the treatment of rheumatism, rheumatoid arthritis (RA), and joint pain. The present study aimed to evaluate the anti-arthritis effects of the cardenolide-rich and caffeoylquinic acid-rich fractions (CDLFs and CQAFs) of P. forrestii in collagen-induced arthritic (CIA) rats, and defined the mechanisms of therapeutic action in MH7A cells treated with TNF-α. Serum rheumatoid factor (RF), TNF-α, IL-6, IL-1β, PGE2, NO, SOD, and MDA were determined by ELISA or other commercially assay kits. Histopathological changes in ankle joint tissues were examined. The mRNA expressions of IL-1β, IL-6, COX-2, and iNOS in MH7A cells were measured by qRT-PCR assays. In addition, the expressions of iNOS, COX-2, and p65 proteins, and the phosphorylation of IκBα, p38, ERK1/2, and JNK proteins in MH7A cells were analyzed by Western blot. The results showed that CDLF and CQAF could suppress the paw swelling in CIA rats at different doses (125 mg/kg, 250 mg/kg, and 500 mg/kg). Histopathological examination suggests that the CDLF and CQAF significantly relieved the damage of the structure of the ankle joint in CIA rats. In addition, serum RF, TNF-α, IL-6, IL-1β, PGE2, NO, and MDA were decreased, along with increased activity of serum SOD. Furthermore, CDLF and CQAF downregulated the expressions of IL-1β, IL-6, COX-2, iNOS, and p65, and inhibited the phosphorylation of IκBα, p38, ERK1/2, and JNK in MH7A cells treated with TNF-α. These findings demonstrated that both CDLF and CQAF exhibited anti-arthritic activity, which might be associated with their inhibitory effects on the NF-κB and MAPK signaling pathways.
Highlights
Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by hyperplasia of the synovial cells, chronic inflammation of the synovium, and the destruction of cartilage and bone [1].Molecules 2018, 23, 1988; doi:10.3390/molecules23081988 www.mdpi.com/journal/moleculesFibroblast-like synoviocytes (FLSs) play a key role in the pathological process of rheumatoid arthritis (RA)
The decrease of weight was reversed by cardenolide-rich fractions (CDLFs) and caffeoylquinic acid-rich fractions (CQAFs) treatments, and there was no significant difference between the weight of the CDLF- or CQAF-treated rats and non-treated control rats (Supplementary Materials Table S1)
In order to elucidate the effective anti-arthritic fraction of P. forrestii ethanol extracts and its molecular mechanisms of therapeutic action, the present study focused on the investigation of the anti-arthritic effects of the CDLF and CQAF obtained from ethanol extracts and their inhibitory effects on the release of inflammatory cytokines, and the activation of NF-κB and MAPK pathways
Summary
Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by hyperplasia of the synovial cells, chronic inflammation of the synovium, and the destruction of cartilage and bone [1]. Abnormal activation of FLS cells leads to the formation of pannus, the degradation of bone, and the release of a large number of inflammation cytokines in the joint, such as TNF-α, IL-6, and IL-1β [2,3] These cytokines can cause inflammation, and speed up the pathological process. TNF-α has been found to be one of the most important cytokines in RA, which can lead to synovial proliferation and the high expressions of related cytokines, including IL-1β, NO, and PGE2 [4,5] Such pathological processes eventually result in the destruction of joint, cartilage, and bone, and even induce deformity or disability [6]. The objectives of the present study included the evaluation of the anti-arthritic effects of the CDLF and CQAF in a CIA rat model, and the investigation of its underlying anti-arthritic mechanisms in MH7A cells treated with TNF-α
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