Flemingia philippinensis Flavonoids Relieve Bone Erosion and Inflammatory Mediators in CIA Mice by Downregulating NF-κB and MAPK Pathways.

Guangchen Sun,Yingqin Liu,Yijie Huang,Congcong Xing,Xin Sun,Luting Zeng

doi:10.1155/2019/5790291

Guangchen Sun, Yingqin Liu + Show 4 more

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https://doi.org/10.1155/2019/5790291

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Abstract

Background The dry root of Flemingia philippinensis has been widely used in the treatment of rheumatism, arthropathy, and osteoporosis in traditional Chinese medicine; the therapeutic effects of Flemingia philippinensis are associated with antiarthritis in traditional Chinese medicine theory. This study was undertaken to investigate the mechanism of bone erosion protection and anti-inflammatory effect of Flemingia philippinensis flavonoids (FPF) in collagen-induced arthritis (CIA) in mice. Methods Flavonoids were extracted from the dry root of Flemingia philippinensis. Collagen-induced arthritis in C57BL/6 mice was used as a rheumatoid arthritis model, and the mice were orally fed with FPF prior to induction to mimic clinical prophylactic therapy for a total of 39 days. After treatment, histology and immunohistochemistry staining were performed, and the levels of anti-collagen type II (CII) antibody and inflammatory mediators, as well as the key proteins of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, were detected in the samples taken from ankle joints, plasma, and paws. Results FPF administration significantly suppressed the paw swelling and arthritic score in CIA mice. FPF reduced inflammatory infiltration and pannus formation, articular cartilage destruction and osteoclast infiltration, and the expression of MMP-9 and cathepsin K in the ankle joint. FPF inhibited plasma anti-CII antibody levels and the production of inflammatory cytokines and chemokines in CIA paws. FPF treatment suppressed the activation of NF-κB as indicated by downregulating the phosphorylation of NF-κB p65 and mitogen-activated protein kinases in CIA paws. Additionally, FPF significantly inhibited inflammation signaling by suppressing the activation of activator protein-1 subset and signal transducers and activators of transcription 3 (STAT3). Conclusions Our data suggest that FPF might be an active therapeutic agent for rheumatoid arthritis and the preventive effect of FPF on arthritis is attributable to an anti-inflammatory effect on CIA by preventing bone destruction, regulating inflammatory mediators, and suppressing NF-κB and MAPK signaling pathways.

Highlights

Flemingia philippinensis (Merr. et Rolfe) is a shrubby herb that belongs to a family of Leguminosae; its roots are popularly used to treat rheumatism, arthropathy, leucorrhea, menalgia, menopausal syndrome, chronic nephritis, and osteoporosis in traditional Chinese medicine [1]
The results suggested that the expressions of matrix metalloproteinases (MMPs)-9 and cathepsin K were significantly inhibited by the treatment of Flemingia philippinensis flavonoids (FPF) as demonstrated by immunohistochemistry and western blot, respectively (Figures 2(d), 2(e), and 5)
FPF alleviated the expression of monocyte chemoattractant protein- (MCP-)1 in the spleen (Figure 7). These results clearly demonstrated that FPF inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) to mediate the production of proinflammatory factors

Summary

Introduction

Flemingia philippinensis (Merr. et Rolfe) is a shrubby herb that belongs to a family of Leguminosae; its roots are popularly used to treat rheumatism, arthropathy, leucorrhea, menalgia, menopausal syndrome, chronic nephritis, and osteoporosis in traditional Chinese medicine [1]. Induction of these inflammatory cytokines is mediated by the signal pathways including nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), activating protein- (AP-) 1 and signal transducers, and activators of transcription 3 (STAT3). This study was undertaken to investigate the mechanism of bone erosion protection and anti-inflammatory effect of Flemingia philippinensis flavonoids (FPF) in collagen-induced arthritis (CIA) in mice. Histology and immunohistochemistry staining were performed, and the levels of anti-collagen type II (CII) antibody and inflammatory mediators, as well as the key proteins of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, were detected in the samples taken from ankle joints, plasma, and paws. Our data suggest that FPF might be an active therapeutic agent for rheumatoid arthritis and the preventive effect of FPF on arthritis is attributable to an anti-inflammatory effect on CIA by preventing bone destruction, regulating inflammatory mediators, and suppressing NF-κB and MAPK signaling pathways

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