Terpenes: Modulating anti-inflammatory signaling in inflammatory bowel disease.

Inflammatory Bowel Disease (IBD) are autoimmune diseases characterized by chronic intestinal inflammation. Considered a western disease, IBD incidence in newly developed countries is skyrocketing. Accordingly, global prevalence is steadily increasing. There are two major IBD phenotypes, ulcerative colitis (UC) and Crohn's disease (CD). UC manifests as uninterrupted inflammation localized in the colon and rectum. Meanwhile, CD presents as interrupted inflammation that can occur throughout the digestive tract. As a result, therapeutics have focused on anti-inflammatory approaches for its treatment. Unfortunately, only 50% of patients benefit from current Food and Drug Administration approved treatments, and all are associated with serious adverse effects. Thus, there is a need for safer and novel therapeutics to increase the efficacy in this population. One aspect that is critical in understanding IBD is how food and phytochemicals therein may be associated with modifying the pathogenesis of IBD. A variety of retrospective and prospective studies, and clinical trials have shown benefits of plant-rich diets on the prevention and symptomatic improvement of IBD. The Mediterranean diet is rich in vegetables, fruits, legumes, and herbs; and characterized by the abundance of anti-inflammatory phytochemicals. An understudied phytochemical class enriched in this diet is terpenes; isoprene-based molecules are widely available in Mediterranean herbs and citrus fruits. Various terpenes have been evaluated in different IBD models. However, some present contradictory or inconclusive results. Therefore, in this review we evaluated preclinical studies of terpenes modulating basic inflammatory signaling related to IBD.

Irilone, a Red Clover Isoflavone, Combined with Progesterone Enhances PR Signaling through the Estrogen and Glucocorticoid Receptors.

Trifolium pratense L. (red clover) is a popular botanical supplement used for women's health. Irilone isolated from red clover previously demonstrated progestogenic potentiation activity. In this study, irilone enhanced progesterone signaling was determined to not occur due to post-translational phosphorylation or by reducing progesterone receptor (PR) protein levels but instead increased PR protein levels in T47D breast cancer cells, which could be blocked by estrogen receptor (ER) antagonists, suggesting an ER dependent effect. Further, irilone increased luciferase activity from a hormone responsive element in a cell line that lacked ER and PR but expressed the glucocorticoid receptor (GR). A siRNA knockdown of GR in Ishikawa PR-B endometrial cancer cells reduced irilone's ability to enhance progesterone signaling. In an ovariectomized CD-1 mouse model, irilone did not induce uterine epithelial cell proliferation. The mechanism of action of irilone gives insight into PR crosstalk with other steroid hormone receptors, which can be important for understanding botanicals that are used for women's health.