Engineering Research Center of Coptis Development & Utilization (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China.
School of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China.
FASEB J. 2024 Sep 30;38(18):e70037. doi: 10.1096/fj.202401624R.
Chronic atrophic gastritis (CAG) is a prevalent preneoplastic condition of the stomach. Palmatine (PAL), an isoquinoline alkaloid isolated from Rhizoma Coptidis (RC), has significant anti-inflammatory properties and is often used to treat gastrointestinal disorders. However, the mechanism of PAL on CAG remains unclear. In this study, N-methyl-N'-nitrosoguanidine (MNNG) was used to induce CAG inflammatory disease models in vivo and in vitro. The efficacy of five alkaloids in RC and the dose-dependent effects of the most effective PAL in CAG mice were evaluated in two animal experiments. RNA-seq and western blot revealed that PAL significantly improved IL-17, TNF, and NF-kappa B inflammation-related signaling pathways. Further hub gene prediction and experimental validation revealed that PAL modulated the STAT1/CXCL10 axis, thereby exerting attenuation of CAG through the regulation of IL-17, TNF-α, and p-p65 expression. In conclusion, PAL was proposed to mitigate MNNG-induced CAG, potentially through the inhibition of oxidative stress and inflammatory responses via the STAT1/CXCL10 axis. This approach is an effective complement to the use of PAL in the treatment of CAG.
慢性萎缩性胃炎（CAG）是一种常见的胃部前瘤状态。黄连（RC）中分离得到的异喹啉生物碱小檗碱（PAL）具有显著的抗炎特性，常用于治疗胃肠道疾病。然而，PAL 对 CAG 的作用机制尚不清楚。在本研究中，使用 N-甲基-N'-亚硝基胍（MNNG）在体内和体外诱导 CAG 炎症疾病模型。在两项动物实验中评估了 RC 中五种生物碱的功效以及最有效的 PAL 在 CAG 小鼠中的剂量依赖性作用。RNA-seq 和 Western blot 表明 PAL 显著改善了与炎症相关的 IL-17、TNF 和 NF-kappa B 信号通路。进一步的枢纽基因预测和实验验证表明，PAL 调节了 STAT1/CXCL10 轴，从而通过调节 IL-17、TNF-α 和 p-p65 的表达来减轻 CAG。总之，PAL 被提出可以减轻 MNNG 诱导的 CAG，可能是通过抑制 STAT1/CXCL10 轴的氧化应激和炎症反应。这种方法是 PAL 治疗 CAG 的有效补充。
