Halofuginone functions as a therapeutic drug for chronic periodontitis in a mouse model

Abstract

Periodontitis is an inflammatory disease caused by host immune response, resulting in a loss of periodontium and alveolar bone. Immune cells, such as T cells and macrophages, play a critical role in the periodontitis onset. Halofuginone, a natural quinazolinone alkaloid, has been shown to possess anti-fibrosis, anti-cancer, and immunomodulatory properties. However, the effect of halofuginone on periodontitis has never been reported. In this study, a ligature-induced mice model of periodontitis was applied to investigate the potential beneficial effect of halofuginone on periodontitis. We demonstrated that the administration of halofuginone significantly reduced the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in vivo, and markedly suppressed immune cell infiltration into the infected sites. Furthermore, we also observed that halofuginone treatment blocked the T-helper 17 (Th17) cell differentiation in vivo and in vitro. We demonstrated for the first time that halofuginone alleviated the onset of periodontitis through reducing immune responses.

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

“…Many studies have used the periodontitis model by placing ligatures inoculated with P. gingivalis around the teeth of the mice to induce massive local accumulation of periodontal pathogens [10,[177][178][179][180][181][182][183][184][185][186][187][188]190,191,194,195]. In a representative study using this model, Li and Amar [188] provided evidence that the mouse periodontal model involving a ligature inoculated with P. gingivalis exhibited a more adequate inflammatory response and greater periodontal tissue breakdown than the control group, which induced periodontitis by ligature alone.…”

Halofuginone, a promising drug for treatment of pulmonary hypertension

“…Recently, it has been shown that halofuginone has therapeutic potential in a mouse model of chronic periodontitis using doses between 0.1 and 1 mg (Wang et al, 2020). Thus, the doses we used for our in vitro and in vivo experiments were within the range previously reported.…”

“…Some studies have further reported that using halofuginone doses between 5 and 400 ng·ml −1 inhibits angiogenesis in vitro (Elkin et al, 2000) and T‐cell activation (Leiba et al, 2006). Recently, it has been shown that halofuginone has therapeutic potential in a mouse model of chronic periodontitis using doses between 0.1 and 1 mg (Wang et al, 2020). Thus, the doses we used for our in vitro and in vivo experiments were within the range previously reported.…”

Interleukin‐37 ameliorates periodontitis development by inhibiting NLRP3 inflammasome activation and modulating M1/M2 macrophage polarization

“…Thus, macrophages participate in the process of inflammation and immune and other pathological activities of periodontal tissues. 33 Recent research has revealed that regulating macrophage polarization is a viable method to ameliorate periodontal inflammation. 34 Indeed, periodontal inflammatory outcomes can be profoundly altered by changes in M1/M2 macrophage ratio.…”

“…In inflamed periodontal sites, macrophages account for approximately 5%–30% of the infiltrating cells. Thus, macrophages participate in the process of inflammation and immune and other pathological activities of periodontal tissues 33 . Recent research has revealed that regulating macrophage polarization is a viable method to ameliorate periodontal inflammation 34 .…”