Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regulation of TLR4/MyD88/NF-κB signaling pathway

Abstract

Background/Aims:Grape seed proanthocyanidin extract (GSPE) has been reported to have a beneficial effect on regulating inf lammation. However, the anti-inflammatory mechanism of GSPE remains unclear. The aim of this study was to verify the influence of GSPE on the Toll-like receptor 4 (TLR4)-mediated signaling pathway in the regulation of murine autoimmune arthritis.Methods:Collagen-induced arthritis (CIA) was induced in dilute brown non-agouti (DBA)/1J mice. The mice were treated with GSPE (0 or 100 mg/kg) intraperitoneally. The severity of arthritis was assessed clinically, biochemically, and histologically. Immunostaining for TLR4 was performed. The expressions of TLR4 and downstream signaling molecules were analyzed by Western blot. The effect of GSPE on lipopolysaccharide (LPS)-induced TLR4 activation was also evaluated using RAW264.7 cells and fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis and from those with osteoarthritis.Results:GSPE attenuated the clinical severity of arthritis and decreased histological damage. GSPE treatment reduced the number of TLR4-stained cells in the synovium of mice with CIA. GSPE also downregulated the expression of TLR4, myeloid differentiation factor 88 (MyD88) and phosphorylated IκBα synovial protein in CIA mice. Concurrently, GSPE inhibited the nuclear translocation of nuclear factor-κB (NF-κB) subunits (p65 and p50). LPS-induced TLR4 activation was suppressed by GSPE in human FLS as well as in murine macrophages in vitro.Conclusions:Our results demonstrated that GSPE ameliorated CIA by regulating the TLR4-MyD88-NF-κB signaling pathway.

Recovery of Chickens Affected with Tibial Dyschondroplasia by Application of Grape Seed Extract through Downregulating CA2 Gene and Enhancing Liver Functions

“…Supplementation of GSE remove the TD lesions, recovered the TD chicks and down-regulated the CA2 expression. Former scholars also reported the downregulation of CA2 expression in rats after the supplementation of GSE (Kim et al, 2018).…”

The protective effects of grape seed oil on induced osteoarthritis of the knee in male rat models

“…Grape seed is well known for its variety of antioxidative derivatives such as oligomeric proanthocyanidins and catechins, as well as anti-inflammatory potentials, is one of the most popular remedies for the treatment of OA [10,11]. Literature reported that the efficacy of grape seed extract administered orally on OA in rats led to the prevention of loss of chondrocyte cells and proteoglycan, formation of osteophytes, reducing reactive oxygen species, and inflammation mediators such as MMP13, nitrotyrosine, and IL-1β, in experimental models [8,12].…”

Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling

“…Indeed, the effects of procyanidins have been demonstrated to be greater than those of its isolated fractions [76,78,79]. Supported by other observations [31,32] and clinical data that have shown that procyanidins from pine bark extract reduce OA pain and inflammation [80,81], our study further suggests that, as generally recognized as safe (GRAS) biologically-active compounds, procyanidins and their active ingredients including procyanidin B2 and procyanidin B3, exert mitigating effects on OA pathogenesis. In particular, our study shows that procyanidins B2 and B3 can largely replicate the mitigating effects of procyanidins in VEGF-mediated OA pathogenesis, highly indicating that these compounds are the active ingredients in procyanidins in OA disease modification.…”

“…In animal studies, grape seed extract, rich with procyanidins, reduce ROS activity and expression of matrix metalloproteinases (MMPs) in the articular cartilage of monosodium iodoacetate-induced OA rats [30], and procyanidins extracted from grape seeds ameliorate collagen-induced arthritis (CIA) in mice through regulation of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway [31]. Notably, daily oral administration of procyanidin B3, one of the components of procyanidins, was shown to mitigate OA pathogenesis in mice subject to medial collateral ligament transection and medial meniscectomy by, at least in part, suppressing induced nitric oxide synthase (iNOS) [32].…”