Chlorogenic acid (CGA), an important biologically active dietary polyphenol, is produced by certain plant species and is a major component of coffee. Reduction in the risk of a variety of diseases following CGA consumption has been mentioned in recent basic and clinical research studies. This systematic review discusses in vivo animal and human studies of the physiological and biochemical effects of chlorogenic acids (CGAs) on biomarkers of chronic disease. We searched PubMed, Embase, Amed and Scopus using the following search terms: ("chlorogenic acid" OR "green coffee bean extract") AND (human OR animal) (last performed on April 1st, 2015) for relevant literature on the in vivo effects of CGAs in animal and human models, including clinical trials on cardiovascular, metabolic, cancerogenic, neurological and other functions. After exclusion of editorials and letters, uncontrolled observations, duplicate and not relevant publications the remaining 94 studies have been reviewed. The biological properties of CGA in addition to its antioxidant and anti-inflammatory effects have recently been reported. It is postulated that CGA is able to exert pivotal roles on glucose and lipid metabolism regulation and on the related disorders, e.g. diabetes, cardiovascular disease (CVD), obesity, cancer, and hepatic steatosis. The wide range of potential health benefits of CGA, including its anti-diabetic, anti-carcinogenic, anti-inflammatory and anti-obesity impacts, may provide a non-pharmacological and non-invasive approach for treatment or prevention of some chronic diseases. In this study, the effects of CGAs on different aspects of health by reviewing the related literatures have been discussed.

Gut microbial dysbiosis is associated with the development of autoimmune disease, but the mechanisms by which microbial dysbiosis affects the transition from asymptomatic autoimmunity to inflammatory disease are incompletely characterized. Here, we identify intestinal barrier integrity as an important checkpoint in translating autoimmunity to inflammation. Zonulin family peptide (zonulin), a potent regulator for intestinal tight junctions, is highly expressed in autoimmune mice and humans and can be used to predict transition from autoimmunity to inflammatory arthritis. Increased serum zonulin levels are accompanied by a leaky intestinal barrier, dysbiosis and inflammation. Restoration of the intestinal barrier in the pre-phase of arthritis using butyrate or a cannabinoid type 1 receptor agonist inhibits the development of arthritis. Moreover, treatment with the zonulin antagonist larazotide acetate, which specifically increases intestinal barrier integrity, effectively reduces arthritis onset. These data identify a preventive approach for the onset of autoimmune disease by specifically targeting impaired intestinal barrier function.

Alcohol consumption is a consistent protective factor for the development of autoimmune diseases such as rheumatoid arthritis (RA). The underlying mechanism for this toleranceinducing effect of alcohol, however, is unknown. Here we show that alcohol and its metabolite acetate alter the functional state of T follicular helper (T FH ) cells in vitro and in vivo, thereby exerting immune regulatory and tolerance-inducing properties. Alcohol-exposed mice have reduced Bcl6 and PD-1 expression as well as IL-21 production by T FH cells, preventing proper spatial organization of T FH cells to form T FH :B cell conjugates in germinal centers. This effect is associated with impaired autoantibody formation, and mitigates experimental autoimmune arthritis. By contrast, T cell independent immune responses and passive models of arthritis are not affected by alcohol exposure. These data clarify the immune regulatory and toleranceinducing effect of alcohol consumption.