Dose‐response assessment of chemically modified curcumin in experimental periodontitis

Abstract

Background CMC2.24, a novel tri‐ketonic chemically modified compound based on natural di‐ketonic curcumin, has been shown to reduce bone loss and inflammatory mediators in experimental periodontitis, however, a potential dose‐response relationship was not determined. The purpose of this study was to assess the effects of different doses of CMC2.24 on inflammation and bone resorption in vivo and also to describe on the effects of CMC2.24 on macrophage response. Methods CMC2.24 was administered daily to animals for 28 days by oral gavage, at the following doses: 0 (control), 1, 3, 10, and 30 mg/kg of body weight. Experimental periodontitis was induced by injections of lipopolysaccharide (LPS) into the gingival tissues. Outcomes assessed were bone resorption, detection of tartrate‐resistant acid phosphatase, and determination of gene expression. In vitro, macrophages (RAW264.7) were treated with different concentrations of CMC2.24: 1, 3, 10, and 30 μM and then subjected to different activation stimuli. Gene expression, phagocytic activity, production of reactive oxygen species (ROS) and cytokine production were evaluated. Results CMC2.24 inhibited bone resorption, osteoclastogenesis, and tumor necrosis factor (TNF)‐α expression in vivo. These beneficial responses reached maximum levels at a dose of 1 mg/kg, i.e. no dose‐dependent effect. In vitro, CMC2.24 reduced the production of TNF‐α and interleukin‐10, inhibited phagocytic activity and stimulated production of ROS. A dose‐dependent effect was observed only for ROS production. Conclusion Low doses of CMC2.24 (1 mg/kg/day) administered orally were sufficient to significantly inhibit alveolar bone resorption associated with the experimental periodontal disease; whereas in vitro macrophage inflammatory gene expression and phagocytosis were reduced, whereas production of ROS was stimulated.

Novel Chemically Modified Curcumin (CMC) Derivatives Inhibit Tyrosinase Activity and Melanin Synthesis in B16F10 Mouse Melanoma Cells

“…Our group has reported on CMC2.24, a triketonic N -phenylaminocarbonyl derivative of bis-demethoxycurcumin, which exhibits enhanced stability and solubility compared to curcumin and has emerged as a ‘lead compound’ for several pharmacological applications such as treatment of anthrax by inhibition of the metalloprotease, lethal factor [ 21 ], treatment of cancers of the pancreas [ 22 ] and prostate [ 23 ], normalizing wound healing in diabetic rats [ 24 ], reduction in severity of periodontitis and inhibition of alveolar bone resorption associated with the disease in a rat model [ 25 , 26 ]. In addition, CMC2.24 has shown superior anti-inflammatory activity compared to the parent compound curcumin, in inhibiting periodontitis-induced bone resorption in rats via multiple mechanisms [ 27 ], and most recently, for the treatment of natural periodontitis in beagle dogs [ 28 , 29 ].…”

Does Chemically Modified Curcumin Control the Progression of Periodontitis? A Systematic Review

“…Seven experimental trials involving 162 rats and 8 dogs were concerned in this systematic review over 14-90 days. 10,13,[16][17][18][19][20] Five articles were published in the USA and two studies were conducted in Brazil. Besides, all studies are contemporary, as the oldest of them was published in 2014.…”

“…Six studies of the selected studies investigated LPSinduced experimental periodontitis, 10,13,[16][17][18][19][20] two studies of them 14,18 worked on diabetes-associated periodontitis, while one study 19 worked on naturally occurring periodontitis. All rodent animals used in six studies 10,13,[16][17][18]20 were male Holtzman rats, which were subjected to bilateral palatal injections of the first molars; 30 µg of lipopolysaccharide (LPS) two weeks, [16][17][18] three weeks, 20 four weeks. 10,13 Escherichia coli diluted in phosphate-buffered saline (PBS) was injected palatally (3 µL) using am10 µL micro-syringe.…”

“…All rodent animals used in six studies 10,13,[16][17][18]20 were male Holtzman rats, which were subjected to bilateral palatal injections of the first molars; 30 µg of lipopolysaccharide (LPS) two weeks, [16][17][18] three weeks, 20 four weeks. 10,13 Escherichia coli diluted in phosphate-buffered saline (PBS) was injected palatally (3 µL) using am10 µL micro-syringe. The opposite sides were received injected with the same quantity of PBS to be considered as a control group (split-mouth study).…”

“…[8][9][10] Many investigations of pre-clinical models and clinical studies 11,12 concluded that Curcumin is a multipurpose molecule with considerable advantageous impacts on inflammatory infections as it has anti-inflammatory, anti-oxidant and anti-microbial features, 8 which make it, propounded as a potent adjunctive factor in periodontal therapy. 10 Because of its inferior bioavailability and short-term life in plasma, it should be delivered in large quantities, which in turn limits its application clinically. 13 This is why curcumin has been chemically modified to enhance its zinc-binding characteristics, improve its solubility and increase its bioavailability.…”