Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Department of General Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, People's Republic of China.
Pharm Biol. 2022 Dec;60(1):1032-1037. doi: 10.1080/13880209.2022.2071450.
Alpinetin, the major active constitutes of Hayata (Zingiberaceae), has been demonstrated to possess the activity of anti-breast cancer. Cytochrome P450 enzymes (CYP450s) plays vital roles in the biotransformation of various drugs.
To assess the effect of alpinetin on the activity of CYP450s and estimate the inhibition characteristics.
The activity of CYP450s was evaluated in pooled human liver microsomes with corresponding substrates and marker reactions. The effect of alpinetin was compared with blank control (negative control) and corresponding inhibitors (positive control). The dose-dependent and time-dependent experiments were conducted in the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM alpinetin and incubated for 0, 5, 10, 15, and 30 min.
Alpinetin suppressed CYP3A4, 2C9, and 2E1 activity. All the inhibitions were significantly influenced by alpinetin contration with the IC values of 8.23 μM (CYP3A4), 12.64 μM (CYP2C9), and 10.97 μM (CYP2E1), respectively. The inhibition of CYP3A4 was fitted with the non-competitive model with a value of 4.09 μM and was time-dependent with and values of 4.67 min and 0.041 μM, respectively. While CYP2C9 and 2E1 were inhibited by alpinetin competitively with values of 6.42 (CYP2C9) and 5.40 μM (CYP2E1), respectively, in a time-independent manner.
The inhibitory effect of alpineticn on CYP3A, 2C9, and 2E1 implied the potential interaction of alpinetin or its origin herbs with the drugs metabolised by those CYP450s, which needs further validation.
山姜素是山姜（姜科）的主要活性成分，已被证明具有抗乳腺癌活性。细胞色素 P450 酶（CYP450s）在各种药物的生物转化中起着至关重要的作用。
评估山姜素对 CYP450 活性的影响，并评估其抑制特性。
在含有相应底物和标记反应的人肝微粒体中评估 CYP450 活性。将山姜素的作用与空白对照（阴性对照）和相应抑制剂（阳性对照）进行比较。在 0、2.5、5、10、25、50 和 100μM 山姜素存在的情况下进行剂量依赖性和时间依赖性实验，并孵育 0、5、10、15 和 30min。
山姜素抑制 CYP3A4、2C9 和 2E1 活性。所有抑制作用均受山姜素浓度的显著影响，IC 值分别为 8.23μM（CYP3A4）、12.64μM（CYP2C9）和 10.97μM（CYP2E1）。CYP3A4 的抑制作用符合非竞争性模型， 值为 4.09μM，具有时间依赖性， 值和 值分别为 4.67min 和 0.041μM。而 CYP2C9 和 2E1 被山姜素竞争性抑制， 值分别为 6.42（CYP2C9）和 5.40μM（CYP2E1），无时间依赖性。
山姜素对 CYP3A、2C9 和 2E1 的抑制作用表明，山姜素或其来源草药可能与这些 CYP450 代谢的药物发生相互作用，这需要进一步验证。
