Melbourne Dental School, The University of Melbourne, 720 Swanston Street, Carlton, VIC, 3053, Australia.
J Cancer Res Clin Oncol. 2020 Jul;146(7):1801-1811. doi: 10.1007/s00432-020-03253-3. Epub 2020 May 20.
Oral mucositis is a debilitating inflammatory disorder observed in patients undergoing active cancer treatment, particularly cancer of the head and neck region. A key pathway believed to be involved in the pathogenesis of oral mucositis is the formation of reactive oxygen species (ROS). The identification of compounds that can inhibit this pathway may therefore be of benefit in treating this disorder. The kava plant (Piper methysticum) contains various constituents, including flavokawain A (FKA), flavokawain B (FKB), yangonin, methysticin and kavain. These constituents are known to be biologically active and possess anti-oxidative properties. This study therefore focused on examining these constituents for their effect on ROS formation in an in vitro oral mucositis model.
Cell proliferation was assessed in normal oral keratinocytes (OKF6) treated with and without kava constituents, namely FKA, FKB, yangonin, methysticin and kavain using an MTS in vitro assay. Oxidative stress was assessed by co-treating and pre-treating OKF6 cells with HO. The effects were quantified by analysis of ROS production, using a CM-H2DCFDA assay.
Pre-treatment of cells for 24 h with 2.5 μg/ml kavain and 5 μg/ml FKA demonstrated a significant protective anti-oxidative effect. Similarly, FKB at a concentration of 2.5 μg/ml, demonstrated a trend of ROS reduction but was observed to be cytotoxic at concentrations greater than 5 μg/ml. Reduction in ROS production by methysticin and yangonin was compromised by their cell cytotoxicity.
This was the first study to identify the anti-oxidative effects and safety of FKA and kavain with regard to oral keratinocytes, highlighting their potential use in the development of a preventative treatment for oral mucositis.
口腔黏膜炎是一种在接受积极癌症治疗的患者中观察到的使人虚弱的炎症性疾病，尤其是头颈部癌症患者。据信，一个关键途径参与了口腔黏膜炎的发病机制，即活性氧（ROS）的形成。因此，鉴定能够抑制该途径的化合物可能有助于治疗这种疾病。卡瓦植物（Piper methysticum）含有各种成分，包括黄烷酮 A（FKA）、黄烷酮 B（FKB）、yangonin、methysticin 和 kavain。这些成分已知具有生物活性，并具有抗氧化特性。因此，本研究集中研究这些成分对体外口腔黏膜炎模型中 ROS 形成的影响。
用 MTS 体外测定法评估正常口腔角质形成细胞（OKF6）在有无卡瓦成分（即 FKA、FKB、yangonin、methysticin 和 kavain）的情况下的细胞增殖。通过用 HO 共同处理和预处理 OKF6 细胞来评估氧化应激。通过使用 CM-H2DCFDA 测定分析 ROS 产生来定量评估效果。
用 2.5μg/ml kavain 和 5μg/ml FKA 预处理细胞 24 小时显示出显著的保护抗氧化作用。同样，浓度为 2.5μg/ml 的 FKB 也表现出降低 ROS 的趋势，但在浓度大于 5μg/ml 时观察到细胞毒性。methysticin 和 yangonin 降低 ROS 产生的作用因细胞毒性而受到影响。
这是第一项研究，确定了 FKA 和 kavain 对口腔角质形成细胞的抗氧化作用和安全性，突出了它们在开发口腔黏膜炎预防治疗方面的潜在用途。
