Yu Weifeng, Chen Shuni, Guan Xiuming, He Guihua, Zhang Wang, Zhang Haiyan, Huang Suiping, Ye Zhenhao, Pan Hudan, Zhong Zishao
State Key Laboratory of Traditional Chinese Medicine Syndrome/Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences/State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangzhou, China; Department of Gastroenterology, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China.
State Key Laboratory of Traditional Chinese Medicine Syndrome/Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences/State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangzhou, China; Department of Spleen and Stomach Diseases, Shenzhen Hospital of Beijing University of Chinese Medicine (Longgang), Shenzhen, China.
Phytomedicine. 2025 Feb;137:156356. doi: 10.1016/j.phymed.2024.156356. Epub 2024 Dec 30.
Chronic atrophic gastritis (CAG) is a precursor to gastric cancer, a leading cause of cancer-related deaths worldwide. Despite current therapeutic strategies, preventing the transition from gastritis to cancer remains a challenge. Traditional Chinese Medicine (TCM), particularly the Yiqi-Huayu-Jiedu (YQHYJD) formula, have exhibited promising results in CAG management. However, the pharmacological underpinnings of this formula remain elusive.
The study aimed to elucidate the pharmacological mechanisms of the YQHYJD formula in treating CAG and its role in inhibiting the progression to gastric cancer through the modulation of the "inflammation-cancer" sequence.
Mass spectrometric analysis of YQHYJD formula-containing serum was conducted to determine the active compounds involved in CAG treatment. A CAG rat model was induced using a combination of deoxycholic acid and ammonia, while a gastric precancerous lesion cell model was generated by exposing GES-1 cells to deoxycholic acid. Both models were treated with varying concentrations of the YQHYJD formula to assess its effects of the JAK2/STAT3 signaling-mediated epithelial-mesenchymal transition (EMT) pathway.
Mass spectrometry analysis identified 80 active compounds in the YQHYJD formula, including quercetin. Network pharmacology analysis revealed that these active compounds may exert their therapeutic effects on CAG through various mechanisms, including the JAK/STAT signaling. Using rat and cellular models of CAG, we found that the JAK/STAT pathway is activated alongside partial epithelial-mesenchymal transition (pEMT). YQHYJD treatment effectively mitigated the activation of the JAK2/STAT3 activation and pEMT. Furthermore, the therapeutic effect of the YQHYJD formula was maintained even in the presence of Colivelin or overexpressed STAT3.
The YQHYJD formula treats CAG by inhibiting the JAK2/STAT3 -mediated pEMT, thereby suppressing the gastric "inflammation-cancer" transformation. This study provides mechanistic insights into the efficacy of YQHYJD in CAG treatment and suggests new therapeutic strategies for preventing gastric cancer development.
慢性萎缩性胃炎（CAG）是胃癌的前驱病变，胃癌是全球癌症相关死亡的主要原因。尽管有目前的治疗策略，但防止胃炎向癌症转变仍然是一项挑战。传统中医（TCM），特别是益气化瘀解毒（YQHYJD）方剂，在CAG的管理中已显示出有前景的结果。然而，该方剂的药理学基础仍然难以捉摸。
本研究旨在阐明YQHYJD方剂治疗CAG的药理机制及其通过调节“炎症-癌症”序列在抑制胃癌进展中的作用。
对含YQHYJD方剂的血清进行质谱分析，以确定参与CAG治疗的活性化合物。使用脱氧胆酸和氨联合诱导建立CAG大鼠模型，同时通过将GES-1细胞暴露于脱氧胆酸建立胃癌前病变细胞模型。两种模型均用不同浓度的YQHYJD方剂处理，以评估其对JAK2/STAT3信号介导的上皮-间质转化（EMT）途径的影响。
质谱分析鉴定出YQHYJD方剂中的80种活性化合物，包括槲皮素。网络药理学分析表明，这些活性化合物可能通过包括JAK/STAT信号在内的多种机制对CAG发挥治疗作用。使用CAG的大鼠和细胞模型，我们发现JAK/STAT途径与部分上皮-间质转化（pEMT）一起被激活。YQHYJD治疗有效地减轻了JAK2/STAT3的激活和pEMT。此外，即使存在Colivelin或过表达的STAT3，YQHYJD方剂的治疗效果仍然保持。
YQHYJD方剂通过抑制JAK2/STAT3介导的pEMT来治疗CAG，从而抑制胃的“炎症-癌症”转化。本研究为YQHYJD治疗CAG的疗效提供了机制性见解，并提出了预防胃癌发展的新治疗策略。
