Chen Li, Xu ShaoYu, Wang Sheng, Chen Hao, Han Yanquan
Institue of Pharmaceutical Department, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, No 117, Meishan Road, Hefei 230031, Anhui, PR China.
Institue of School of Pharmacy, Anhui University of Chinese Medicine, No 350, Longzihu Road, Hefei 230012, Anhui, PR China.
Phytomedicine. 2025 Jan;136:156346. doi: 10.1016/j.phymed.2024.156346. Epub 2024 Dec 25.
Xiaohua Funing Tang (XHFND) is a decoction formula of traditional Chinese medicine (TCM) and possesses the potential to manage chronic atrophic gastritis (CAG) with liver depression and spleen deficiency (LDSD), but the mechanisms were still unclear.
Our aim is to reveal the overall synergistic mechanisms of XHFND against CAG with LDSD.
Based on a CAG rat model with LDSD, this study combined metabolomics, gut microbiota, and network pharmacology techniques to demonstrate the XHFND mechanisms with multiple components and targets.
Through the integration analysis of gut microbiome and metabolome using metorigin, we found that XHFND regulates arginine metabolism levels in the urea cycle by regulating the gut ecological environment and the host. The XHFND mainly promotes aspartate 1 metabolism by regulating the abundance of odoribacter, bacteroides, phocaeicola, lachnospire, and intestinimonas, intervened in the imbalance of arginine metabolism in CAG rats with LDSD, suppresses the pathogenic Th17 cell differentiation, and inhibits the gastric mucosa damage in rats. Through Cytoscape analysis of network pharmacology and metabolomics integration, we found that XHFND might regulate host phospholipid metabolism through PTEN and PIK3CA to inhibit the PI3K-AKT-TSC axis and then inhibit mTORC1 to control arginine metabolism in the urea cycle and produce polyamines, thereby inhibiting the pathogenic Th17 cell differentiation and preventing rat gastric mucosa damage. Intervention in arginine metabolism in the urea cycle is the primary pathway in which XHFND exerts its therapeutic effects. XHFND may mainly control the pathogenic Th17 cell differentiation in the gastric mucosa of model rats through the pathway.
This study indicated that XHFND might intervene in treating CAG with LDSD from multiple levels and perspectives to suppress the pathogenic Th17 cell differentiation, which aligns with the characteristics of TCM treatment. This study presents experimental evidence for the clinical use of XHFND and promotes the development of drugs for the therapy of CAG with LDSD.
小华茯苓汤（XHFND）是一种中药汤剂，具有治疗肝郁脾虚型慢性萎缩性胃炎（CAG）的潜力，但其作用机制尚不清楚。
本研究旨在揭示小华茯苓汤治疗肝郁脾虚型慢性萎缩性胃炎的整体协同作用机制。
基于肝郁脾虚型慢性萎缩性胃炎大鼠模型，本研究结合代谢组学、肠道微生物群和网络药理学技术，以阐明小华茯苓汤多成分、多靶点的作用机制。
通过使用metorigin对肠道微生物组和代谢组进行整合分析，我们发现小华茯苓汤通过调节肠道生态环境和宿主来调节尿素循环中的精氨酸代谢水平。小华茯苓汤主要通过调节奥氏杆菌、拟杆菌、福氏菌、毛螺菌和肠单胞菌的丰度来促进天冬氨酸1代谢，干预肝郁脾虚型慢性萎缩性胃炎大鼠精氨酸代谢失衡，抑制致病性Th17细胞分化，并抑制大鼠胃黏膜损伤。通过对网络药理学和代谢组学整合结果进行Cytoscape分析，我们发现小华茯苓汤可能通过PTEN和PIK3CA调节宿主磷脂代谢，抑制PI3K-AKT-TSC轴，进而抑制mTORC1，以控制尿素循环中的精氨酸代谢并产生多胺，从而抑制致病性Th17细胞分化并预防大鼠胃黏膜损伤。干预尿素循环中的精氨酸代谢是小华茯苓汤发挥治疗作用的主要途径。小华茯苓汤可能主要通过该途径控制模型大鼠胃黏膜中致病性Th17细胞的分化。
本研究表明，小华茯苓汤可能从多个层面和角度干预肝郁脾虚型慢性萎缩性胃炎的治疗，以抑制致病性Th17细胞分化，这符合中医治疗的特点。本研究为小华茯苓汤的临床应用提供了实验依据，并推动了肝郁脾虚型慢性萎缩性胃炎治疗药物的研发。
