Application of green tea polyphenols in prevention and management of autoimmune disorders associated with Sjogren''s syndome.
The pathogenesis of autoimmune diseases is multifaceted, and the complexity of symptoms, diagnosis and treatment options associated with these diseases reflects this. Sjogren’s syndrome (SS) is an autoimmune disorder affecting up to 4 million Americans, and results from autoimmune reactions in secretory glands (primary SS) and other tissues (secondary SS). Current treatment options for SS are aimed largely at amelioration of symptoms, but without functional restoration of the secretory glands. Prescribed medications for salivary hypofunction or xerostomia are often associated with severe side effects, typically due to the effects of systemically administered muscarinic cholinergic receptor agonists.
Recently published data indicate that in addition to inflammation, oxidative damage of glandular cells and reduction in antioxidant enzyme levels are associated with SS salivary gland pathology. Initial findings in SS patients strongly support the idea that the pathogenesis of SS involves a combination of inflammation, oxidative damage, and reduced antioxidant capacity. This combination can also be found in other autoimmune diseases such as psoriasis, and provides a novel target for the development of new diagnostic tools.
Importantly, animal models for SS and psoriasis have shown that these pathological abnormalities could be improved with non-toxic agents, such as green tea polyphenols, that inhibit inflammation and hyperproliferation, and elevate the antioxidant capacity in autoimmune-affected tissues.
These newly published observations warrant further exploration of new targets and novel agents for treatment of autoimmune disorders.
My laboratory is investigating the underlying mechanisms associated with the protective effects of green tea polyphenols against autoimmune diseases. One of our projects is to identify early-detection and therapeutic-responding biomarkers associated with autoimmune-induced destruction of secretory gland cells. The goal of this study is to understand the mechanisms associated with EGCG-mediated regulation in salivary epithelial cells prior to autoimmune activity, and elucidate novel mechanisms associated with disease-onset and EGCG intervention in a mouse model specifically for SS. This project is supported by NIH/NIDCR 1R15DE019836-01 grant.
My research also involves in clinical trials using patent-pending formulation of green tea extract to manage xerostomia. This project is a collaborative effort among dentist, pathologist, salivary function expert, and biostatistician. Our team has won the 2011 IADR/GSK Innovation in Oral Care Award, which supports our clinical trial entitled “Effects of a natural proprietary formulation for patients with clinically diagnosed xerostomia”. The goal of this clinical trial is tocharacterize protein biomarkers, include proliferating cell nuclear antigen (PCNA, marker for oxidative DNA damage repair), Ki-67 (marker for cell proliferation), peroxiredoxin 6 and glutathione peroxidase-1 (markers for antioxidant capacity) in biopsy samples of minor salivary glands obtained during diagnosis; and to clinically evaluate the efficacy of an all-natural formula to control xerostomia.
In addition, research in our laboratory resulted in several intellectual properties and patent filings.