Abstract 146: Chebulinic acid ameliorates Liposaccharide induced bone loss and ROS production via suppressing NF-κB activation

Objective/Backgrounds: Inflammation, a common phase during bone healing is reported to negatively affect bone regeneration. Inflammatory bone loss conditions like periodontitis, inflammatory arthritis and periprosthetic osteolysis, all driven by Lipopolysaccharide (LPS), which has been identified as a key pathogenic agent. Infact, inflammatory bone diseases not only associated with generation of inflammatory cytokines but also produce local oxidative stress by intracellular reactive oxygen species (ROS). Till date, there are limited therapeutic approaches for inflammation triggered osteoblast differentiation inhibition. Chebulinic acid (CA), a plant ellagitannin derived from fruits of Triphala (Terminalia Chebula) reported to exhibits anti-inflammatory & anti-oxidant activity. However, its role in preventing inflammatory bone loss condition induced by lipopolysaccharide (LPS) remains unknown. Methods: For LPS induced inflammatory bone loss model, 10wk old male C57BL/6J mice were taken & divided into Control (PBS), LPS, and LPS (5 mg/kg; IP injection) +CA (10 mg/kg; orally) groups. After 21 days, bones and serum were collected; micro-CT analysis, Elisa and histomorphometric evaluation were conducted. In vitro, murine osteoblasts were treated with vehicle, LPS (800 ng) and LPS+CA (10 nM). Thereafter, cell differentiation, viability and proliferation, Inflammatory behaviour, Cellular & mitochondrial oxidative stress, and NFkBsignalling were determined. Results: Our results shows that LPS inhibited bone remodelling, formation& regeneration, and also promoted oxidative stress accumulation within cell by producing inflammatory cytokines. Upon Chebulinic acid (CA) administration, LPS-induced bone destruction &biochemical changes ameliorated with marked protective effect by enhancing bone formation invivo. In osteoblast cells, LPS treatment causes osteoblast dysfunction by increased ROS at cellular & mitochondria levels with enhanced expression of inflammatory cytokines. Chebulinic acid (CA) improves the inhibitory effect of LPS on osteoblast functions by enhancing cell differentiation and proliferation. Moreover, CA inhibited the oxidative stress & mitochondrial dysfunction stimulated by LPS treatment by blocking increased secretion of inflammatory cytokines Mechanistically, CA presented remarkable protective effects against LPS treatment by blocking NFkBsignalling. Discussion/Conclusions: Our results proclaim the protective role of CA against LPS-induced inflammatory bone loss & inhibitory effect on total ROS levels and inflammation. Collectively, Chebulinic acid holds as a potential novel therapeutic strategy for inflammatory diseases in bones.