Project

Regulation of Inflammation by Natural Product extracts: Role in osteoclastogenesis

Inflammation is the body’s endeavor at self-defense, the intent being to eradicate harmful stimuli, including damaged cells, irritants, or pathogens and begin the healing process.  It is one of the major steps in normal wound healing process with overlapping events such as formation of granulation tissue, angiogenesis, and tissue remodeling. However, chronic inflammation can also lead to a host of diseases. Thus the inflammatory response plays a key role in both health protection and disease generation. Osteoclasts are the multinuclear cells specialized for bone resorption, playing a crucial role in bone remodeling. Osteoclasts have been known to differentiate from hematopoietic precursors of the monocyte/macrophage lineage in the presence of macrophage-colony stimulating factor (M-CSF or CSF-1) and receptor activator of ΝF-κΒ ligand (RANKL). Inflammatory cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor alpha (TNF-α), as well as lipopolysaccharide (LPS) have been reported to induce osteoclast formation indirectly by stimulating osteoblasts. Chronic inflammation can lead to an abnormal increase in osteoclastic bone resorption and excessive bone destruction as observed in osteoporosis, rheumatoid arthritis, and periodontal disease (PD) etc. The use of herbal or natural medicines for the management of diverse disorders has an extensive and widespread history. The present study is focused on identifying and characterizing Natural Products that are potent modulators in regulating inflammasomes, which play a crucial role in the inflammation process. Further studies will also be aimed at understanding the activation and downstream regulation of inflammasomes by IL-1β, IL-18, NFκB, MAPK and ERK pathways