Design, synthesis, and evaluation of mono‐carbonyl analogues of curcumin (MCACs) as potential antioxidants against periodontitis

Abstract

Background and objective:The application of curcumin is limited by its instability.Mono-carbonyl analogues of curcumin (MCACs) are structurally stable, yet the intermediate bridging ketones in their skeletons account for increased toxicity. This study aimed to synthesize and screen MCACs that exhibit low cytotoxicity and high antioxidant ability, and the effects of MCACs on experimental periodontitis were also investigated. Materials and methods:The cytotoxicity of MCACs on MC3 T3-E1 was determined by MTT assay. The antioxidant capacity was investigated by the cell viability against H 2 O 2 -induced damage and the level of reactive oxygen species (ROS) and malondialdehyde (MDA). The localization and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was detected by immunofluorescence and western blot, respectively. In addition, MCAC was intragastrically administrated in rats with ligature-induced experimental periodontitis. The effects were assessed by bone resorption, as well as the immunohistology staining of inflammatory and oxidative stress markers.Results: MCACs with cyclopentanone and containing pyrone showed lower toxicity than natural curcumin were synthesized (1A-10A, 1H-10H), among which, 1A exhibited the most potent cytoprotective effect against H 2 O 2 -induced damage. Such effects could be explained by the reduced MDA and ROS level, possibly through the nucleus translocation of Nrf2 and the induction of HO-1. Micro-CT results further indicated that 1A significantly reduced bone loss, along with an increased level of Nrf2 and HO-1, and decreased TNFα and IL-1β. Conclusion:The present study has synthesized a novel antioxidant MCAC 1A with good biosafety and stability. MCAC 1A could serve as a host response modulator with preventive and protective effects on periodontitis.

Advances in the study of traditional Chinese medicine affecting bone metabolism through modulation of oxidative stress

“…Almost all metabolic processes in the body, such as glucose metabolism, lipid metabolism, and bone metabolism, are influenced by oxidative stress. The main targets of oxidative stress are proteins and nucleic acids, which affect various aspects of organismal function through multiple levels and mechanisms, including cell apoptosis and necrosis (Zhao et al, 2021). Mitochondria, as the primary cellular organelles generating ROS, are directly damaged by the excessive ROS at the subcellular level.…”

Curcumin Attenuates Periodontal Injury via Inhibiting Ferroptosis of Ligature-Induced Periodontitis in Mice

“…For example, curcumin can protect against renal damage in rhabdomyolysis-AKI via attenuating the characteristic changes of lipid peroxidation and GSH depletion in ferroptosis [ 26 ]. Curcumin may play a crucial role in the treatment of periodontitis, and this role may be decided by the strong antioxidant capacity of curcumin related to scavenging excessive ROS [ 27 , 28 ]. In animal models of periodontitis, curcumin down-regulated the inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and suppressed bone resorption by the suppression of RANKL expression [ 29 , 30 ].…”

Deuterohemin-Ala-His-Thr-Val-Glu-Lys (DhHP-6) Mimicking Enzyme as Synergistic Antioxidant and Anti-Inflammatory Material for Periodontitis Therapy

“…Increasing research has focused on the effect of oxidative stress, caused by excessive ROS, on the occurrence and development of periodontitis [ 5 ]. Vitamin C, an antioxidant, can increase the number of collagen bundles in periodontal tissue, which is beneficial for the treatment of periodontitis [ 5 , 6 ] as antioxidants, resveratrol, and curcumin can improve the antioxidant defense ability of periodontal ligament cells and reduce the inflammatory response in periodontitis [ 5 , 7 ]. However, the maintenance of the oxidative balance requires the continuous input of antioxidants.…”