Chemically-Modified-Curcumins Inhibit Alveolar Bone Loss in Diabetic Rats with Peiodontitis

Objective: To determine the effect of chemically-modified-curcumins (CMCs) on alveolar bone loss (ABL) and gelatinases (MMPs) in gingiva (and skin) during diabetes and endotoxin-induced periodontitis.

Method: Diabetes was induced in adult male rats by streptozotocin injection; non- diabetic rats served as controls. E. Coli LPS was injected into maxillary gingiva. Two different CMCs, 2.23, 2.24, were administered by oral gavage (30mg/kg) daily. Untreated diabetics received vehicle alone. After three weeks, the rats were sacrificed and gingiva, skin and jaws were collected. The maxillary jaws were dissected and x-rayed. The gingival tissues were excised, pooled per experimental group (n=6 rats per group), extracted and partially purified and, together with skin samples, analyzed for MMP-2 and MMP-9 by gelatin zymography.

Result: Diabetes (and LPS injection) increased interproximal alveolar bone loss by 59.5% and CMC 2.24 decreased the excessive ABL by 27% (P = 0.04). Of the two compounds tested, only CMC 2.24 reduced bone loss to near-normal values. The elevated gelatinase activity (MMP-2&9) in the gingiva of the diabetic animals was reduced by CMC 2.24. CMC 2.24 also appears to reduce skin gelatinase activity (MMP 2) by reducing the ratio of pro MMP-2 to active MMP-2 (P=0.0012) and reducing the percentage of conversion of pro MMP-2 into active MMP-2 (P=0.03) which may result from decreased MMP-14 activation of pro MMP-2.

Conclusion: Of the two novel compounds tested, only one CMC (2.24) appeared to effectively reduce alveolar bone loss and MMPs (MMP-9 in gingiva and MMP-2 in skin). Of interest, this compound is also a most effective inhibitor of MMPs in vitro and cytokine production in cell culture and may be therapeutically effective in periodontal and other diseases.

Grant supported from The Center for Advanced Biotechnology, Stony Brook University, (NYSTAR grant #A43273), Chem. Master Intl., Inc.