Background and objectives: Although apigenin exhibits various biological effects, its anti-inflammatory role in the periodontal field remains unknown. We examined the anti-inflammatory effects of apigenin and the underlying mechanism in nicotine- and lipopolysaccharide (LPS)-stimulated human periodontal ligament (hPDL) cells.
Materials and methods: Western blotting was used to examine the effect of apigenin (10-40 microM) on the LPS- and nicotine-induced expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and heme oxygenase-1 (HO-1), as well as the phosphorylation of mitogen-activated protein kinases (MAPKs), in hPDL cells. Pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-12 were monitored using Griess reagents and ELISA.
Results: Incubation of hPDL cells with apigenin decreased LPS- and nicotine-induced HO-1 protein expression and activity. Apigenin significantly inhibited the nicotine- and LPS-induced production of NO, PGE2, IL-1beta, TNF-alpha, IL-6, and IL-12, and the upregulation of iNOS and COX-2 in hPDL cells. Hemin, a selective HO-1 inducer, reversed the apigenin-mediated suppression of nicotine- and LPS-induced NO, PGE2 and cytokine production. Treatment with inhibitors of the phosphoinositide 3-kinase, MAPKs, p38, and JNK, as well as a protein kinase C inhibitor, blocked the anti-inflammatory effects of apigenin in nicotine- and LPS-treated cells.
Conclusions: Apigenin possesses anti-inflammatory activity in hPDL cells and works through a novel mechanism involving the action of HO-1. Thus, apigenin may have potential benefits as a host modulatory agent in the prevention and treatment of periodontal disease associated with smoking and dental plaque.