6‐Shogaol, an active ingredient of ginger, inhibits osteoclastogenesis and alveolar bone resorption in ligature‐induced periodontitis in mice

Abstract

BackgroundPeriodontitis is an inflammatory disease of the tissues surrounding teeth that causes destruction of connective tissues. During the progress of periodontitis, osteoclasts are solely accountable for the resorption of alveolar bones that leads to the loss of teeth if not properly treated. Thus, the development of effective anti‐resorptive therapies will greatly benefit the treatment of periodontitis patients. In the present study, we suggest an inhibitory effect of 6‐shogaol, an ingredient of ginger, on osteoclast differentiation and bone resorption.MethodsMouse bone marrow cells were cultured in the presence of macrophage‐colony stimulating factor and receptor activator of nuclear factor‐κB ligand (RANKL) to investigate the effect of 6‐shogaol on osteoclast differentiation and intracellular signaling pathways. 6‐shogaol significantly reduced osteoclast differentiation, actin ring formation, and resorption. In the presence of 6‐shogaol, osteoclast signaling including the RANKL‐induced activation of mitogen‐activated protein kinases, Ca2+ oscillation, generation of reactive oxygen species, and nuclear factor of activated T‐cells, cytoplasmic 1 nuclear translocation was significantly inhibited in vitro. Furthermore, a ligature‐induced periodontitis model in mice was used to determine the role of 6‐shogaol in vivo.ResultsThe administration of 6‐shogaol prevented osteoclastogenesis and alveolar bone resorption induced by ligature. Furthermore, the ligature‐induced number of macrophages and neutrophils as well as the expression of interleukin‐1β and tumor necrosis factor‐α were considerably lower in the periodontal tissues following shogaol injection.ConclusionThese results confirm the anti‐osteoclastogenic effect of 6‐shogaol and suggest the possibility of application as an anti‐resorptive strategy in periodontitis.

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

“…Administration of 6-shogaol prevented osteoclastogenesis and alveolar bone resorption caused by ligature-induced periodontitis, decreased the number of macrophages and neutrophils, and considerably downregulated the expression of IL-1β and TNF-α in periodontal tissue. These results confirmed that 6-shogaol had anti-osteoclastogenic effects and suggested its potential application as an anti-resorptive treatment in periodontitis [233].…”

Therapeutic potential of ginger against COVID-19: Is there enough evidence?

“… 86 In an animal periodontitis model, treatment with 6-shogaol reduces the macrophage numbers, avoids bone destruction, inhibits the osteoclast maturation and activation, and downregulates IL-1β, TNF-α, and ROS. 87 Similarly, 6-gingerol prevents osteoclast differentiation and represses IL-1-induced PGE2 synthesis in mouse osteoblasts. 88 Moreover, zingerone restores the renal functions and declines the generation of TNF-α, IL-1β, IL-6 and ROS in animal models of nephropathy.…”

Effect of ginger ( Zingiber officinale ) supplementation on oxidative stress parameters: A systematic review and meta‐analysis

“…Moreover, it is believed that ginger exerts potent anti‐oxidant functions by scavenging ROS and restoring the balance between anti‐oxidant/oxidant homeostasis (Reddy et al., 2014; Shanmugam et al., 2011). Recent research has shown that 6‐shogaol is one of the main active ingredients of ginger (Kim et al., 2020). Based on previous findings, 6‐shogaol rich ginger extract may lead to an improved antioxidant defense system via the induction of HO‐1 and the nuclear factor E2‐related factor2 (Nrf2)/antioxidant response element (ARE) pathway.…”