Sappanchalcone has been demonstrated to possess several biological effects. However, the molecular mechanism underlying these effects is not fully understood. In this study, we examined the effects of sappanchalcone on hydrogen peroxide (H(2)O(2))-induced cytotoxicity using human dental pulp (HDP) cells, and lipopolysaccharide (LPS)-induced inflammation using human periodontal ligament (HPDL) cells. Sappanchalone concentration proportionately increased heme oxygenase (HO)-1 protein expression and enzyme activity in both HDP and HPDL cells. It also protected HDP cells from H(2)O(2)-induced cytotoxicity and reactive oxygen species production. The cytoprotective effect of sappanchalcone was nullified by HO-1 inhibitor, Tin protoporphyrin (SnPP). Sappanchalcone is seen to inhibit LPS-stimulated nitric oxide (NO), prostaglandin E(2) (PGE(2)), interlukine-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interlukine-6 (IL-6) and interlukine-12 (IL-12) release in addition to inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in HPDL cells. SnPP, a specific inhibitor of HO-1, partly blocked sappanchalcone mediated suppression of inflammatory mediator production, in LPS-stimulated HPDL cells. HDP and HPDL cells treated with sappanchalcone exhibited the transient activation of c-Jun NH2-terminal kinase (JNK) and NF-E2-related factor-2 (Nrf2). The expression of HO-1 protein by sappanchalcone was significantly reduced by pretreatment with JNK inhibitor. In conclusion, induction of HO-1 is an important cytoprotective mechanism by which sappanchalcone protects HDP cells from H(2)O(2) and in addition it also exhibits anti-inflammatory effects in LPS-stimulated HPDL cells. Thus, sappanchalcone could potentially be a therapeutic approach for periodontal, pulpal and periapical inflammatory lesion.
Copyright 2010. Published by Elsevier B.V.