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

Abstract

Periodontitis is a chronic infectious disease characterized by the destruction of connective tissue and alveolar bone that eventually leads to tooth loss. Ferroptosis is an iron-dependent regulated cell death and is involved in ligature-induced periodontitis in vivo. Studies have demonstrated that curcumin has a potential therapeutic effect on periodontitis, but the mechanism is still unclear. The purpose of this study was to investigate the protective effects of curcumin on alleviating ferroptosis in periodontitis. Ligature-induced periodontal-diseased mice were used to detect the protective effect of curcumin. The level of superoxide dismutase (SOD), malondialdehyde (MDA) and total glutathione (GSH) in gingiva and alveolar bone were assayed. Furthermore, the mRNA expression levels of acsl4, slc7a11, gpx4 and tfr1 were measured using qPCR and the protein expression of ACSL4, SLC7A11, GPX4 and TfR1 were investigated by Western blot and immunocytochemistry (IHC). Curcumin reduced the level of MDA and increased the level of GSH. Additionally, curcumin was proven to significantly increase the expression levels of SLC7A11 and GPX4 and inhibit the expression of ACSL4 and TfR1. In conclusion, curcumin plays a protective role by inhibiting ferroptosis in ligature-induced periodontal-diseased mice.

Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

“…But the targets that through them ferroptosis is inhibited are different from those in cancer cells. In acute lung injury and Parkinson's disease, the main mechanism is attributed to the activation of NRF2 signaling (Deng et al, 2023;Lin et al, 2022), while in asthma and spinal cord injury, these effects are exerted through suppressing the immune response and, Id2/transferrin pathway, respectively (Wang, Li, Wang, Chen, & Goh, 2023;Wang, Li, Wang, Zhu, Liu, et al, 2023;Wang, Lin, Huang, Liu, Chen, et al, 2023;Wang, Liu, Li, Zha, Chen, et al, 2023;Wang, Shen, Lian, Deng, Qu, et al, 2023;Wang, Tan, Zhang, Wu, & Shi, 2023;Wang, Wan, Peng, Zhao, Bai, & Hu, 2023). This dual role, modulating NRF2 signaling, suppressing immune response, or affecting specific pathways, emphasizes the need for a nuanced understanding of quercetin's effects in different contexts.…”

“…Amentoflavone (AMF) is a natural biflavonoid compound isolated from plants such as ginkgo, hinoki, and St. John's wort (Tuli et al, 2023). Its anticancer features have been linked to its ability to induce cell cycle arrest, apoptosis, and autophagy alongside hindering metastasis and angiogenesis via modulating pathways such as the AMPK/mTOR pathway (Xiong et al, 2021), which is implicated in ferroptosis as well (Wang, Li, Wang, Chen, & Goh, 2023;Wang, Li, Wang, Zhu, Liu, et al, 2023;Wang, Lin, Huang, Liu, Chen, et al, 2023;Wang, Liu, Li, Zha, Chen, et al, 2023;Wang, Shen, Lian, Deng, Qu, et al, 2023;Wang, Tan, Zhang, Wu, & Shi, 2023;Wang, Wan, Peng, Zhao, Bai, & Hu, 2023). AMF has been shown to cause ferroptotic death in gastric cancer via downregulating a transcription factor named ATF2 and decreasing its target genes, including GPX4 and SLC7A11.…”

“…In osteoarthritis, curcumin safeguards chondrocytes from erastin-induced ferroptosis by upregulating the Nrf2 signaling pathway, which in turn reverses lipid ROS and Fe 2+ production (Zhou, Jia, et al, 2023). Additionally, curcumin's protective role extends to ligature-induced periodontitis, where it inhibits ferroptosis in periodontal-diseased mice by reducing MDA levels and modulating key ferroptosis-related proteins, including ACSL4, SLC7A11, GPX4, and TfR1 (Wang, Li, Wang, Chen, & Goh, 2023;Wang, Li, Wang, Zhu, Liu, et al, 2023;Wang, Lin, Huang, Liu, Chen, et al, 2023;Wang, Liu, Li, Zha, Chen, et al, 2023;Wang, Shen, Lian, Deng, Qu, et al, 2023;Wang, Tan, Zhang, Wu, & Shi, 2023;Wang, Wan, Peng, Zhao, Bai, & Hu, 2023). In hepatolenticular degeneration, curcumin's efficacy lies in its ability to expel copper and inhibit ferroptosis through the Nrf2/HO-1/GPX4 signaling pathway (Sun et al, 2023).…”

“…Preclinical investigations underscore curcumin's auspicious anti- Despite the imperative for subsequent clinical substantiation, curcumin, with its multifaceted biological activities, emerges as a compelling natural compound for cancer therapeutics (Wang, Li, Wang, Chen, & Goh, 2023;Wang, Li, Wang, Zhu, Liu, et al, 2023;Wang, Lin, Huang, Liu, Chen, et al, 2023;Wang, Liu, Li, Zha, Chen, et al, 2023;Wang, Shen, Lian, Deng, Qu, et al, 2023;Wang, Tan, Zhang, Wu, & Shi, 2023;Wang, Wan, Peng, Zhao, Bai, & Hu, 2023). Due to a wide range of studies regarding the role of curcumin in the induction of ferroptosis in cancer, we try to categorize the studies based on their targets.…”

Mechanism of DYRK1a in myocardial ischemia–reperfusion injury by regulating ferroptosis of cardiomyocytes

“…Ferroptosis is a newly discovered iron‐dependent, regulated cell death program, clearly defined in 2012, characterized by excessive iron and concomitant accumulation of lipid hydroperoxides 7 . MDA, GSH, GPX4, SLC7A11, ACSL4, and TFR1 are commonly encoded proteins or genes related to ferroptosis, all of which are involved in the oxidative system and lipid metabolism 8,9 . The mechanism by which ferroptosis regulates cardiomyocyte function remains largely unknown and may involve complex molecular processes.…”