The health effects of pomegranate and pomegranate juice have been associated withthe high content in antioxidantpolyphenols and particularly in ellagitannins (punicalagins). The health effects of ellagitannin-containing products can be associated with gut-produced urolithins, and thus the evaluation of the biological effects of these metabolites is essential. Phytoestrogens / PhytoSERMs are widely known plant compounds that bind to ER and affect the physiology of various systems. Mounting evidence point out that PhytoSERMs exert estrogenic effects on skeleton, affects favourably the cardiovascular function and menopausal symptoms while demonstrate antiestrogenic actions on the breast and prostate tissue. Recent research, has shown preliminary evidence of the anti-inflammatory, anticarcinogenic, antiglycative, antioxidant, and antimicrobial effects of urolithins as phyto SERM, supporting their potential contribution to the health effects attributed to pomegranate.

Steroid hormone receptors (SRs) are ligand-activated transcription factors and sensors for growth factor-initiated signaling pathways in hormonally regulated tissues, such as the breast, and Thyroid. Several protein kinases are rapidly activated in response to steroid hormone binding to cytoplasmic SRs. Induction of rapid signaling upon SR ligand binding ensures that receptors and coregulators are appropriately phosphorylated as part of optimal transcription complexes. Kinases are emerging as key mediators of SR action. Cross talk between SR and membrane-initiated signaling events suggests a mechanism for coordinate regulation of gene subsets by mitogenic stimuli in hormonally responsive normal tissues; such cross talk is suspected to contribute to cancer biology.

We are working along with Dr.Sabu Thomas, RGCB to understand the role of microflora involved in conversion of active constituents of ellagitannins in to urolithins. Pomegranate ellagitannins are not absorbed intact into the blood stream but are hydrolyzed to ellagic acid over several hours in the intestine. Ellagitannins are also metabolized into urolithins by gut flora. It is therefore conceivable that the health effects of ellagitannin-containing products can be associated with these gut-produced urolithins. Production of these microbe-derived metabolites is subject to high inter individual variability. So understanding the importance of the microflora and its inter individual variability is main focus of the study.

27 hydroxycholesterol is an oxysterol and has been reported to have selective estrogen receptor modulatory activity. It has been reorted to have deleterious effects in bone, cardiovascular health and breast cancer. In breast cancer it is known to act via ER alpha and LXR receptors. But the mechanisms related to modification at epigenetic levels still remain a mystery. In our lab we are trying to unveil the major players at epigenetic level in 27HC mediated breast cancer proliferation in collaboration with Dr. Arumugam Rajavelu, RGCB.