Periploca forrestii saponin ameliorates CIA via suppressing proinflammatory cytokines and nuclear factor kappa-B pathways

Abstract

ObjectivePeriploca forrestii Schltr has been used as a Chinese folk medicine for the treatment of rheumatism, arthralgia and fractures. However, the anti-arthritic activity of Periploca forrestii saponin (PFS) and the active compound has still not been revealed. This study aimed to investigate the protective effects and mechanisms of PFS on collagen type II (CII) collagen-induced arthritis (CIA) mice. We sought to investigate whether PFS and Periplocin could regulate osteoclastogenesis, and if so, further investigation on its mechanism of action.MethodsArthritis was induced in female BALB/c mice by CIA method. PFS was administered at a dose of 50 mg/kg body weight once daily for five weeks. The effects of treatment in mice were assessed by histological and biochemical evaluation in sera and paws. Anti-osteoclastogenic action of PFS and Periplocin was identified using an osteoclast formation model induced by RANKL.ResultsPFS ameliorated paw erythema and swelling, inhibited bone erosion in ankle joint histopathological examination. PFS treatment resulted in decreased IgG2a, and increased IgG1 levels in the serum of CIA mice. Decreased TNF-α, and increased interleukin (IL)-4 and IL-22 levels were also found in PFS-treated mice. PFS inhibited the I-κBα phosphorylation, blocked nuclear factor (NF)-κB/p65 phosphorylation and abrogated AP-1/c-Fos activity. PFS downregulated toll-like receptor (TLR) 4, STAT3 and MMP-9 expression in CIA mice and RANKL-induced osteoclastogenesis. PFS and Periplocin inhibited RANKL-induced osteoclast formation in a dose dependent manner within nongrowth inhibitory concentration, and PFS decreased osteoclastogenesis-related marker expression, including cathepsin K and MMP-9.ConclusionThis study revealed that the protective mechanism of PFS on CIA was associated with regulatory effects on proinflammatory factors and further on the crosstalk between NF-κB and c-Fos/AP-1 in vivo and in vitro. Therefore, PFS is a promising therapeutic alternative for the treatment of RA, evidencing the need to conduct further studies that can identify their active components in treating and preventing RA.

A New Peracetylated Oleuropein Derivative Ameliorates Joint Inflammation and Destruction in a Murine Collagen-Induced Arthritis Model via Activation of the Nrf-2/Ho-1 Antioxidant Pathway and Suppression of MAPKs and NF-κB Activation

“…CIA induction resulted in the development of a pronounced synovitis associated with an autoimmune response against cartilage with inflammatory cells infiltrate and production of many cytokines and matrix-degrading, accompanying cartilage degradation and bone erosions [31,32]. Our results revealed, for the first time, that Per-OL and OL supplemented diets exhibited preventive effects in the development of inflammation and joint damage in SD-CIA.…”

Saponin from Periploca forrestii Schltr Mitigates Oxazolone-Induced Atopic Dermatitis via Modulating Macrophage Activation

“…In the course of inflammatory disease, NF- κ B activation controls the production of proinflammatory mediators, such as NO and its mediator protein iNOS, PGE2 and its mediator protein COX2, and cytokines IL-6 and TNF- α [ 61 ]. In the previous study, PFS was found to have inhibited the phosphorylation of p65 and its inhibitory protein (I κ B) [ 31 ]. We deservedly further investigate the inhibitory effects of PFS on this critical transcription factor.…”

“…Our previous studies demonstrated that P. forrestii saponin (PFS) inhibits murine arthritis by suppressing cytokine production, local inflammation, and systemic autoimmune responses; PFS and its active compound periplocin also inhibit osteoclastogenesis by reducing proteinases and phosphorylation of NF- κ B p65 and its inhibitory protein (I κ B) [ 30 , 31 ]. In the present study, we further affirmed the anti-AD effect of PFS using the oxazolone-induced AD-like mouse model and elucidated the underlying molecular mechanisms of its action, providing evidence of the utilization of PFS for treating AD.…”

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

“…Collagen-induced arthritis (CIA) in mice was performed according to the methodology with minor changes [20]. Chicken collagen type II (CII) was dissolved in 0.1 M glacial acetic acid to a final concentration of 2 mg/ml CII, and the solution was emulsified in an equal volume of Complete Freund's Adjuvant (CFA containing 4 mg/ml mycobacterium tuberculosis) overnight at 4°C.…”