Li Dawei, Lin Yuxin, Lv Xia, Wu Yuzhuo, Han Chaoyan, Cao Peng, Zhang Guixin, Leng Aijing, Zhou Jian, Wang Chao
The First Affiliated Hospital of Dalian Medical University, Dalian, China.
College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, China.
Front Pharmacol. 2024 Nov 15;15:1485209. doi: 10.3389/fphar.2024.1485209. eCollection 2024.
(), which possesses various biological effects, has been widely used as traditional medicine and functional food in Asian countries, especially China. In consideration of its various biological effects on human healthcare, . was usually used in combination with other drugs. However, the potential drug-drug interaction induced by . through cytochrome P450 enzymes (CYPs) remain unknown.
Using the activity assay of CYPs, the inhibitory effects of and its constituents could be evaluated. The interference of on the metabolic processes of clinical drugs could be investigated. The chemical constituents of . could be identified using LC-MS. The interaction between bioactive compounds and CYPs could be proposed through docking analysis and molecular dynamics.
The dichloromethane extract of . could inhibit various CYP450 subtypes and interfere with the pharmacokinetics of four drugs in rats. Triterpenoids were identified as the main constituents of the dichloromethane extract by Q-TOF-MS in preliminary analyses. Then, a triterpenoid library containing 66 compounds was established to evaluate their inhibitory effects against CYP 1A2, 2D6, 3A4, 2A6, 2B6, 2C9, and 2C19. CYP 1A2 was inhibited by most lanostane triterpenoids, indicating a strong affinity for these compounds. Among triterpenoids, compound displayed a broad inhibitory effect against CYPs, except for CYP 3A4, 2D6, 2C9, and 2C19. Finally, compounds and exhibited interference with the metabolism of 16 drugs through the inhibition of CYPs . In silico molecular docking analyses for assaying the interaction between compound and CYPs indicated that the hydrogen bonds formed between the hydroxyl groups and amino acid residues.
. displayed broad inhibitory effects on CYPs, with triterpenoids as the main bioactive constituents, which may induce potential drug-drug interaction. This information should be helpful for the rational use of . in promoting human health.
（）具有多种生物学效应，在亚洲国家，尤其是中国，已被广泛用作传统药物和功能性食品。鉴于其对人类健康的多种生物学效应，（）通常与其他药物联合使用。然而，（）通过细胞色素P450酶（CYPs）诱导的潜在药物相互作用仍不清楚。
使用CYPs的活性测定法，可以评估（）及其成分的抑制作用。可以研究（）对临床药物代谢过程的干扰。可以使用液相色谱-质谱联用（LC-MS）鉴定（）的化学成分。通过对接分析和分子动力学可以提出生物活性化合物与CYPs之间的相互作用。
（）的二氯甲烷提取物可以抑制多种CYP450亚型，并干扰大鼠体内四种药物的药代动力学。在初步分析中，通过四极杆飞行时间质谱（Q-TOF-MS）鉴定三萜类化合物是二氯甲烷提取物的主要成分。然后，建立了一个包含66种化合物的三萜类化合物库，以评估它们对CYP 1A2、2D6、3A4、2A6、2B6、2C9和2C19的抑制作用。大多数羊毛甾烷型三萜类化合物抑制CYP 1A2，表明这些化合物对其具有很强的亲和力。在三萜类化合物中，化合物（）对CYPs表现出广泛的抑制作用，但对CYP 3A4、2D6、2C9和2C19除外。最后，化合物（）和（）通过抑制CYPs对16种药物的代谢产生干扰。用于分析化合物（）与CYPs之间相互作用的计算机模拟分子对接分析表明，羟基与氨基酸残基之间形成了氢键。
（）对CYPs表现出广泛的抑制作用，三萜类化合物是主要的生物活性成分，这可能会诱导潜在的药物相互作用。这些信息有助于（）在促进人类健康方面的合理使用。
