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Design, synthesis, and evaluation of mono‐carbonyl analogues of curcumin (MCACs) as potential antioxidants against periodontitis
Author(s) -
Zhao Ya,
Zheng Zhiwei,
Zhang Menghan,
Wang Yi,
Hu Rongdang,
Lin Weijia,
Huang Chenyang,
Xu Chuchu,
Wu Jianzhang,
Deng Hui
Publication year - 2021
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/jre.12862
Subject(s) - curcumin , chemistry , malondialdehyde , oxidative stress , reactive oxygen species , viability assay , antioxidant , cytotoxicity , periodontitis , pharmacology , western blot , heme oxygenase , biochemistry , superoxide dismutase , toxicity , heme , microbiology and biotechnology , apoptosis , medicine , biology , in vitro , enzyme , gene , organic chemistry
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 TNF‐α 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.