Epigallocatechin-3-gallate ameliorates both obesity and autoinflammatory arthritis aggravated by obesity by altering the balance among CD4+ T-cell subsets.

Epigallocatechin-3-gallate (EGCG) is the most biologically active catechin in green tea. EGCG has been shown to have therapeutic effects in autoinflammatory diseases and obesity. Obesity is currently regarded-partly-as an inflammatory condition because of the inflammatory cytokines and higher Th1 cell differentiation detected in obese animal models and human cohort studies. In this work, the effects of EGCG on diet-induced obesity (DIO) mice and obese collagen-induced arthritis (CIA) mice were investigated. EGCG reduced the body weight and fat infiltration in liver tissue while improving serum lipid profiles in DIO mice. EGCG also induced a higher Treg/Th17 cell ratio in CD4(+) T-cell differentiation by decreasing the ratio of STAT3/STAT5 expression in DIO mice. EGCG was also effective in obese CIA mice. Reducing Th17 cells and increasing regulatory T (Treg) cells by affecting the STAT protein ratio were important effects of EGCG that might result in improved arthritic scores and levels of several inflammatory indicators. Thus, EGCG has an anti-inflammatory effect by suppressing STAT3 proteins and Th17-cell differentiation. EGCG thus shows promise for treating autoimmune conditions related to STAT3 or Th17 cells, such as metabolic syndrome, inflammatory arthritis, and some neoplastic diseases.

Grape-seed proanthocyanidin extract as suppressors of bone destruction in inflammatory autoimmune arthritis.

Chronic autoimmune inflammation, which is commonly observed in rheumatoid arthritis (RA), disrupts the delicate balance between bone resorption and formation causing thedestruction of the bone and joints. We undertook this study to verify the effects of natural grape-seed proanthocyanidin extract (GSPE), an antioxidant, on chronic inflammation and bone destruction. GSPE administration ameliorated the arthritic symptoms of collagen-induced arthritis (CIA), which are representative of cartilage and bone destruction. GSPE treatment reduced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and osteoclast activity and increased differentiation of mature osteoblasts. Receptor activator of NFκB ligand expression in fibroblasts from RA patients was abrogated with GSPE treatment. GSPE blocked human peripheral blood mononuclear cell-derived osteoclastogenesis and acted as an antioxidant. GSPE improved the arthritic manifestations of CIA mice by simultaneously suppressing osteoclast differentiation and promoting osteoblast differentiation. Our results suggest that GSPE may be beneficial for the treatment of inflammation-associated bone destruction.

Retinal attenuates inflammatory arthritis by reciprocal regulation of IL-17-producing T cells and Foxp3(+) regulatory T cells and the inhibition of osteoclastogenesis.

Retinoids (e.g., vitamin A and its derivatives) can regulate immune responses. The aim of this study was to determine whether all-trans retinaldehyde (retinal), a vitamin A derivative, can inhibit inflammatory responses and joint destruction in DBA/1J mice with collagen-induced arthritis (CIA). The arthritis score and incidence of arthritis were lower in mice treated with retinal compared to those treated with cottonseed oil. Histopathologic evidence of joint damage was lower in mice treated with retinal, corresponding with a reduction in the infiltration of immune cells in mice treated with retinal type II collagen (CII)-stimulated spleen cells. In addition, the expression of proinflammatory cytokines, oxidative stress proteins, and osteoclast markers were significantly reduced in mice treated with retinal. In vitro, retinal induced increased Foxp3 expression and inhibited Th17 development. The proportion of Foxp3(+) Treg cells was increased in the spleens of mice treated with retinal, whereas the proportion of Th17 cells was reduced. In both mice and a human culture system, tartrate-resistant acid phosphatase (TRAP) positive mononuclear cells and multinucleated cells were significantly reduced after treatment with retinal. The expression of osteoclast differentiation markers was dramatically decreased upon addition of retinal. This is the first study to demonstrate the therapeutic effect of retinal on an autoimmune arthritis model in mice through reciprocal regulation of Th17 and regulatory T cells and protection of differentiation and activation of osteoclasts. Taken together, our findings indicate that retinal has profound immunoregulatory functions and potential value for the treatment of autoimmune inflammatory disorders.