Lu Qiang, Wang Jiahao, Tang Ying, Li Wenna, Li Cailan
Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
Food Funct. 2025 Feb 3;16(3):1100-1115. doi: 10.1039/d4fo04991h.
(), one of the most common infectious pathogens in the world, can cause gastritis, digestive ulcers, and even gastric cancer. urease (HPU) is a distinctive virulence factor of that allows it to be distinguished from other pathogens. Dried ginger is a famous edible and medicinal herb that is commonly used to prevent and treat gastrointestinal tract-related diseases. In this study, phytochemical analysis of the aqueous extract of dried ginger (DGE) and the inhibition of DGE on was investigated. Subsequently, we evaluated the inhibitory activity of DGE against enzymes including HPU and jack bean urease (JBU) and determined its potential mechanism of action. UPLC-ESI-MS/MS analysis indicated that a total of 63 compounds including seven glycosides, nine terpenoids, two esters, seven phenols, eight lignans, five phenylpropanoids, and four phenolic acids were identified in DGE. DGE was observed to inhibit the growth of four strains (ATCC 43504, NCTC 26695, SS1, and ICDC 111001) with minimum inhibitory concentration (MIC) values spanning the range of 0.05 to 1.50 mg mL. Moreover, DGE has higher enzyme inhibitory activity on HPU (IC = 0.49 ± 0.01 mg mL) than on JBU (IC = 0.54 ± 0.01 mg mL). Enzyme inhibitory kinetic analysis revealed that the inhibition type of DGE against HPU was slow-binding and anti-competitive, whereas it was slow-binding and mixed type on JBU. A further mechanism study indicated that the protective effect of sulfhydryl-containing compounds on enzyme activity was significantly better than that of inorganic compounds, indicating that the action site of DGE inhibition of enzyme was the sulfhydryl residue. The results of DTT reactivation experiments showed that the DGE-urease complex was reversible. Furthermore, molecular docking investigation showed that the main components of DGE interacted with sulfhydryl groups and Ni. In conclusion, DGE effectively inhibited the growth of and the activity of its key virulence factor urease. And the in-depth study of the kinetic characteristics and the mechanism of action showed that the active site sulfhydryl group and Ni might be the targets of urease inhibition by DGE. Our study may provide experimental evidence for the traditional application of dried ginger in the treatment of -associated gastric diseases.
（幽门螺杆菌）是世界上最常见的传染性病原体之一，可引起胃炎、消化性溃疡，甚至胃癌。幽门螺杆菌脲酶（HPU）是幽门螺杆菌一种独特的毒力因子，使其能够与其他病原体区分开来。干姜是一种著名的药食两用草本植物，常用于预防和治疗胃肠道相关疾病。在本研究中，对干姜水提取物（DGE）进行了植物化学分析，并研究了DGE对幽门螺杆菌的抑制作用。随后，我们评估了DGE对包括HPU和刀豆脲酶（JBU）在内的酶的抑制活性，并确定了其潜在作用机制。超高效液相色谱-电喷雾串联质谱（UPLC-ESI-MS/MS）分析表明，在DGE中总共鉴定出63种化合物，包括七种糖苷、九种萜类、两种酯类、七种酚类、八种木脂素、五种苯丙素和四种酚酸。观察到DGE对四种幽门螺杆菌菌株（ATCC 43504、NCTC 26695、SS1和ICDC 111001）的生长具有抑制作用，最低抑菌浓度（MIC）值范围为0.05至1.50 mg/mL。此外，DGE对HPU（IC = 0.49 ± 0.01 mg/mL）的酶抑制活性高于对JBU（IC = 0.54 ± 0.01 mg/mL）。酶抑制动力学分析表明，DGE对HPU的抑制类型为慢结合和反竞争性，而对JBU则为慢结合和混合型。进一步的机制研究表明，含巯基化合物对酶活性的保护作用明显优于无机化合物，表明DGE抑制酶的作用位点是巯基残基。二硫苏糖醇（DTT）再激活实验结果表明，DGE-脲酶复合物是可逆的。此外，分子对接研究表明，DGE的主要成分与巯基和镍相互作用。总之，DGE有效抑制了幽门螺杆菌的生长及其关键毒力因子脲酶的活性。对动力学特征和作用机制的深入研究表明，活性位点巯基和镍可能是DGE抑制脲酶的靶点。我们的研究可能为干姜在治疗幽门螺杆菌相关胃病中的传统应用提供实验证据。
