Yang Penghui, Yang Hongmei, Zhou Hengli, Li Qiuyue, Wei Sufen, Wang Qi, Yan Yan, Liu Yongqiang, Pan Huafeng, Li Siyi
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
Department of Emergency Ward, The First Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, 550001, China.
Chin Med. 2022 Sep 9;17(1):104. doi: 10.1186/s13020-022-00663-y.
We aimed to explore how weipiling (WPL) decoction WPL alleviates gastric precancerous lesions (GPLs) and uncover its anti-inflammatory roles in GPL treatment.
The anti-GPL action mechanisms of WPL were analysed using a network pharmacological method. The WPL extract was prepared in a traditional way and evaluated for its major components using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). BALB/c mice were exposed to N-methyl-N-nitro-N-nitrosoguanidine (MNNG) (150 μg/mL) for 6 weeks to induce GPLs. GPL mice were administered WPL (3.75 g/kg/day and 15 g/kg/day) for an additional 8 weeks. Haematoxylin and eosin (H&E) staining was used to investigate histological alterations in gastric tissues. Expression of the T helper 1 (Th1) cell markers CD4 and interferon-gamma (INF-γ) were tested using immunohistochemistry (IHC). Inflammatory protein and mRNA levels in the nuclear factor kappa B (NF-κB) pathway were detected using western blotting and a quantitative reverse transcription polymerase chain reaction (RT-qPCR), respectively.
We identified and selected 110 active compounds and 146 targets from public databases and references. Four representative components of WPL were established and quantified by HPLC-MS/MS analysis. WPL attenuated MNNG-induced GPLs, including epithelial shedding, cavity fusion, basement membranes with asymmetrical thickness, intestinal metaplasia, dysplasia, pro-inflammatory Th1-cell infiltration, and INF-γ production, indicating that WPL prevents inflammation in the gastric mucosa. Furthermore, WPL reversed MNNG-induced activation of the IκB/NF-κB signalling pathway and subsequently attenuated the upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase (NOX)) family members NOX2 and NOX4.
WPL attenuated GPLs by controlling the generation of pro-inflammatory elements and inhibiting the NF-κB signalling pathway in vivo.
我们旨在探讨萎皮苓（WPL）汤如何减轻胃黏膜上皮内瘤变（GPLs），并揭示其在GPL治疗中的抗炎作用。
采用网络药理学方法分析WPL抗GPL的作用机制。采用传统方法制备WPL提取物，并使用高效液相色谱-串联质谱（HPLC-MS/MS）对其主要成分进行评估。将BALB/c小鼠暴露于N-甲基-N-硝基-N-亚硝基胍（MNNG）（150μg/mL）中6周以诱导GPLs。给GPL小鼠额外灌胃WPL（3.75g/kg/天和15g/kg/天）8周。采用苏木精-伊红（H&E）染色法研究胃组织的组织学变化。使用免疫组织化学（IHC）检测辅助性T细胞1（Th1）细胞标志物CD4和干扰素-γ（INF-γ）的表达。分别使用蛋白质免疫印迹法和定量逆转录聚合酶链反应（RT-qPCR）检测核因子κB（NF-κB）途径中的炎症蛋白和mRNA水平。
我们从公共数据库和参考文献中鉴定并筛选出110种活性化合物和146个靶点。通过HPLC-MS/MS分析确定并定量了WPL的四种代表性成分。WPL减轻了MNNG诱导的GPLs，包括上皮脱落、腔隙融合、基底膜厚度不对称、肠化生、发育异常、促炎性Th1细胞浸润和INF-γ产生，表明WPL可预防胃黏膜炎症。此外，WPL逆转了MNNG诱导的IκB/NF-κB信号通路激活，随后减弱了诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）和烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH氧化酶（NOX））家族成员NOX2和NOX4的上调。
WPL通过控制促炎因子的产生和抑制体内NF-κB信号通路减轻GPLs。
