Cao Jun-Hua, Xue Rui, He Biao
Department of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.
Immunopharmacol Immunotoxicol. 2021 Oct;43(5):519-526. doi: 10.1080/08923973.2021.1948565. Epub 2021 Jul 26.
Cytokines can induce a chronic inflammatory response in the periodontium, leading to periodontitis. Quercetin, a naturally occuring flavonoid, has been shown to inhibit periodontitis, but how it works is poorly understood. In this study, we assessed the impact of quercetin on lipopolysaccharide (LPS)-induced inflammatory damage in oral mucosal keratinocytes (hOMK107) and explored its underlying mechanism.
The viability and apoptosis of hOMK107 cells were measured after exposure to LPS, followed or not by quercetin. The production of IL-1β, IL-6, IL-8, TNF-ɑ, iNOS, and COX-2 was quantified by enzyme-linked immunosorbent assay (ELISA), while levels of Akt, AMPK, and mTOR and their phosphorylation were detected semi-quantitatively by western blotting.
Quercetin significantly improved cell viability and apoptosis by reversing LPS-induced upregulation of Bax and downregulation of Bcl-2 in hOMK107 cells. Quercetin decreased the production of IL-1β, IL-6, IL-8, TNF-ɑ, iNOS, and COX-2, as well as signal transduction the Akt/AMPK/mTOR pathway. Inhibitors of Akt, AMPK, and mTOR strengthened the anti-apoptotic effects of quercetin, while agonists of Akt, AMPK, or mTOR or Akt overexpression weakened the anti-apoptotic effects.
These results indicate that quercetin may have a potential protective effect against the chronic inflammation-related periodontitis suppressing Akt/AMPK/mTOR pathway.
细胞因子可在牙周组织中引发慢性炎症反应，导致牙周炎。槲皮素是一种天然存在的类黄酮，已被证明可抑制牙周炎，但其作用机制尚不清楚。在本研究中，我们评估了槲皮素对脂多糖（LPS）诱导的口腔黏膜角质形成细胞（hOMK107）炎症损伤的影响，并探讨了其潜在机制。
将hOMK107细胞暴露于LPS后，再给予或不给予槲皮素，检测细胞活力和凋亡情况。通过酶联免疫吸附测定（ELISA）定量检测白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、肿瘤坏死因子-α（TNF-α）、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的产生，同时通过蛋白质免疫印迹法半定量检测Akt、AMPK和mTOR及其磷酸化水平。
槲皮素通过逆转LPS诱导的hOMK107细胞中Bax上调和Bcl-2下调，显著提高细胞活力并改善细胞凋亡。槲皮素降低了IL-1β、IL-6、IL-8、TNF-α、iNOS和COX-2的产生，以及Akt/AMPK/mTOR信号通路的转导。Akt、AMPK和mTOR的抑制剂增强了槲皮素的抗凋亡作用，而Akt、AMPK或mTOR的激动剂或Akt过表达则削弱了槲皮素的抗凋亡作用。
这些结果表明，槲皮素可能通过抑制Akt/AMPK/mTOR信号通路对慢性炎症相关的牙周炎具有潜在的保护作用。
