Ou Ling, Chen Meiyun, Peng Chang, Chen Haobo, Hao Yajie, Chen Qingchang, Feng Zhong, Yao Meicun, Kong Xianhe
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong, China.
Discipline of Chinese and Western Integrative Medicine, Jiangxi University of Chinese Medicine, Nanchang, China.
Front Cell Infect Microbiol. 2025 Jul 22;15:1603128. doi: 10.3389/fcimb.2025.1603128. eCollection 2025.
(HP) is a major gastric pathogen linked to chronic gastritis, peptic ulcers, and gastric cancer. The emergence of antibiotic resistance has prompted the search for alternative treatments. Helile formula, derived from the ancient "Taiping Shenghuifang," is known to treat various degrees of diarrhea and has potential for treating gastrointestinal disorders. However, the antibacterial efficacy, material basis, and action mechanisms of the helile formula against HP remain undetermined.
The chemical constituents were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and high-performance liquid chromatography (HPLC). The anti-HP activity and underlying mechanisms were investigated through a series of assays, including the determination of minimum inhibitory concentration (MIC), N-phenyl-1-naphthylamine (NPN) uptake assay, scanning electron microscopy (SEM) to observe morphological changes, cell viability and cell adhesion activity assays, assessment of nitric oxide (NO) production, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for gene expression analysis. For the anti-HP infection study and mechanism exploration, techniques such as hematoxylin and eosin (H&E) staining for histological examination, enzyme-linked immunosorbent assay (ELISA) for cytokine and antibody quantification, 16S ribosomal DNA (16S rDNA) sequencing for microbial community profiling, and metabolomics for global metabolite analysis were employed.
Multiple constituents of helile formula, namely ellagic acid, gallic acid, chebulagic acid, chebulic acid, and corilagin, were identified. , helile formula increased bacterial outer-membrane permeability, disrupted HP structure, inhibited toxin-related genes, and suppressed cell adhesion. In male Kunming mice, helile formula effectively reversed HP-induced inflammation. It modulated key metabolites, such as adenine, panaxytriol, 4-hydroxyglutamate semialdehyde, and N-alpha-Acetyl-L-lysine. It influenced the gut microbiota, especially families like and . Adenine, in particular, repaired HP-caused damage to GES1 cells, reduced HP - mediated cell adhesion, and inhibited HP-induced interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production.
These findings demonstrated the remarkable anti-HP efficacy of the helile formula and , suggesting that the helile formula represents a highly promising therapeutic candidate for the management of HP infections.
幽门螺杆菌（HP）是一种主要的胃部病原体，与慢性胃炎、消化性溃疡和胃癌有关。抗生素耐药性的出现促使人们寻找替代治疗方法。源自古代《太平圣惠方》的和胃理肠方已知可治疗不同程度的腹泻，并且具有治疗胃肠道疾病的潜力。然而，和胃理肠方对幽门螺杆菌的抗菌效果、物质基础和作用机制仍未确定。
使用超高效液相色谱 - 串联质谱法（UPLC - MS/MS）和高效液相色谱法（HPLC）分析化学成分。通过一系列实验研究其抗幽门螺杆菌活性及潜在机制，包括测定最低抑菌浓度（MIC）、N - 苯基 - 1 - 萘胺（NPN）摄取实验、扫描电子显微镜（SEM）观察形态变化、细胞活力和细胞黏附活性实验、评估一氧化氮（NO）产生以及逆转录 - 定量聚合酶链反应（RT - qPCR）进行基因表达分析。对于抗幽门螺杆菌感染研究和机制探索，采用了苏木精和伊红（H&E）染色进行组织学检查、酶联免疫吸附测定（ELISA）定量细胞因子和抗体、16S核糖体DNA（16S rDNA）测序分析微生物群落谱以及代谢组学进行全局代谢物分析等技术。
鉴定出和胃理肠方的多种成分，即鞣花酸、没食子酸、诃子次酸、诃子酸和柯里拉京。和胃理肠方增加细菌外膜通透性，破坏幽门螺杆菌结构，抑制毒素相关基因，并抑制细胞黏附。在雄性昆明小鼠中，和胃理肠方能有效逆转幽门螺杆菌诱导的炎症。它调节关键代谢物，如腺嘌呤、人参三醇、4 - 羟基谷氨酸半醛和N - α - 乙酰 - L - 赖氨酸。它影响肠道微生物群，特别是[此处原文缺失相关菌群名称]等菌属。特别是腺嘌呤修复了幽门螺杆菌对GES1细胞造成的损伤，减少幽门螺杆菌介导的细胞黏附，并抑制幽门螺杆菌诱导的白细胞介素 - 6（IL - 6）和肿瘤坏死因子 - α（TNF - α）产生。
这些发现证明了和胃理肠方显著的抗幽门螺杆菌功效，表明和胃理肠方是治疗幽门螺杆菌感染极具前景的候选药物。
