Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Berberine inhibits inflammatory bone resorption via bitter taste receptors.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhang Zhiying, Li Zixia, Liu Jiaxin, Li Yixuan, Jia Yinan, Xie Jing, Zheng Xin, Tizzano Marco, Zheng Liwei, Xu Xin
Аннотация
BACKGROUND: Extra-gustatory bitter taste receptors (Tas2rs) have been identified as critical regulators of host inflammation and immune responses. Berberine, a bitter natural alkaloid, has demonstrated effectiveness against bone resorption. However, the potential involvement of Tas2rs-mediated signaling in the anti-resorptive effects of berberine remains to be investigated.
PURPOSE: This study aims to elucidate the mechanisms of action of berberine in mitigating inflammatory bone resorption through Tas2rs-mediated pathways.
MATERIALS AND METHODS: The expression of bitter taste receptors in mouse bone marrow-derived macrophages (BMDMs) was confirmed through re-analysis of public RNA-seq datasets and in vitro experiments. The specific cellular responses induced by berberine were examined using Tas2r126-mediated calcium imaging and siRNA knockdown techniques. Additionally, we explored the mechanisms through which berberine affects osteoclastic differentiation in BMDMs and validated its effectiveness against inflammatory bone resorption using systemic inflammatory bone resorption and periapical periodontitis models in Gα-gustducin-deficient (Gnat3⁻/⁻) mice.
RESULTS: We confirmed the expression of multiple Tas2rs along with downstream effectors Gnat3 and phospholipase C-β2 (Plcβ2) in mouse BMDMs. Among these, Tas2r126 was the most highly expressed bitter taste receptor and could be activated by berberine, resulting in decreased osteoclastogenesis via the Tas2r126/Gnat3/cAMP/NF-κB p65 pathway. Furthermore, the activation of Gnat3-mediated signaling by berberine significantly inhibited both systemic and periapical inflammatory bone resorption in mice.
CONCLUSION: Berberine inhibits the osteoclastic differentiation of BMDMs through the Tas2r126/Gα-gustducin/cAMP/NF-κB p65 pathway, effectively suppressing both systemic and alveolar bone resorption in mice. This study reveals a novel mechanism by which berberine influences osteoclastogenesis and suggests a promising phytotherapeutic approach against inflammatory bone resorption by targeting bitter taste signaling with natural bitter compounds.
PURPOSE: This study aims to elucidate the mechanisms of action of berberine in mitigating inflammatory bone resorption through Tas2rs-mediated pathways.
MATERIALS AND METHODS: The expression of bitter taste receptors in mouse bone marrow-derived macrophages (BMDMs) was confirmed through re-analysis of public RNA-seq datasets and in vitro experiments. The specific cellular responses induced by berberine were examined using Tas2r126-mediated calcium imaging and siRNA knockdown techniques. Additionally, we explored the mechanisms through which berberine affects osteoclastic differentiation in BMDMs and validated its effectiveness against inflammatory bone resorption using systemic inflammatory bone resorption and periapical periodontitis models in Gα-gustducin-deficient (Gnat3⁻/⁻) mice.
RESULTS: We confirmed the expression of multiple Tas2rs along with downstream effectors Gnat3 and phospholipase C-β2 (Plcβ2) in mouse BMDMs. Among these, Tas2r126 was the most highly expressed bitter taste receptor and could be activated by berberine, resulting in decreased osteoclastogenesis via the Tas2r126/Gnat3/cAMP/NF-κB p65 pathway. Furthermore, the activation of Gnat3-mediated signaling by berberine significantly inhibited both systemic and periapical inflammatory bone resorption in mice.
CONCLUSION: Berberine inhibits the osteoclastic differentiation of BMDMs through the Tas2r126/Gα-gustducin/cAMP/NF-κB p65 pathway, effectively suppressing both systemic and alveolar bone resorption in mice. This study reveals a novel mechanism by which berberine influences osteoclastogenesis and suggests a promising phytotherapeutic approach against inflammatory bone resorption by targeting bitter taste signaling with natural bitter compounds.