Notopterol (NOT) is a major bioactive ingredient extracted from the rhizomes of either Notopterygium incisum Ting ex H. T. Chang or N. forbesii Boiss (Qianghuo in Chinese), a botanical drug that was adopted as a traditional Chinese medicine. NOT is suggested to show analgesic and anti-inflammatory effects in clinical practice. The inhibitory effects of NOT on human cytochrome P450 enzymes were investigated in the present study. Our results indicate that NOT inhibited the activity of CYP2D6 in a time-, concentration- and NADPH-dependent manner. The values of K_I and k_inact were 10.8 μM and 0.62 min⁻¹, respectively. The calculated k_obs at 10 μM was 0.29 min⁻¹, above the 0.02 min⁻¹ risk level. After incubation with NOT at 10 μM for 9 min, approximately 92% of CYP2D6 activity was inhibited. Such loss of enzyme activity was not restored through dialysis, which indicates that the observed enzyme inhibition was irreversible. Partition ratio of the inactivation was approximately 29. Quinidine, a competitive CYP2D6 inhibitor, demonstrated protection on enzymes against the NOT-induced inactivation, but such protection was not found in incubation systems fortified with glutathione or catalase/superoxide dismutase. Additionally, CYP3A4 was observed to function as an enzyme mainly involved in the biotransformation of NOT. Taken together, these findings indicate that NOT served as a mechanism-based inactivator of CYP2D6, meanwhile, those observed effects may induce the latent drug-drug interactions. The metabolic activation of NOT may be the key to trigger the inactivation of the enzyme.

Notopterol（NOT）是一种主要的生物活性成分，是从HT Chang或In。forbesii Boiss（强国）（一种被用作中药的植物）的根茎线虫的根茎中提取的。在临床实践中，建议不要将NO显示镇痛和抗炎作用。在本研究中研究了NO对人细胞色素P450酶的抑制作用。我们的结果表明，NOT以时间，浓度和NADPH依赖性方式抑制CYP2D6的活性。的值ķ_我和ķ _INACT分别为10.8  μ M和0.62分钟^-1分别。计算的k_OBS在10  μ中号为0.29分钟^-1，0.02分钟以上^-1风险级别。与NOT孵育10之后 μM持续9分钟，CYP2D6活性的约92％被抑制。通过透析不能恢复这种酶活性的损失，这表明观察到的酶抑制是不可逆的。灭活的分配比例约为29。一种竞争性CYP2D6抑制剂奎尼丁显示对酶具有保护作用，以防止NOT诱导的灭活，但在以谷胱甘肽或过氧化氢酶/超氧化物歧化酶强化的培养系统中未发现这种保护作用。另外，观察到CYP3A4起主要参与NOT生物转化的酶的作用。综上所述，这些发现表明NOT不作为CYP2D6的基于机制的灭活剂，同时，这些观察到的作用可能会诱导潜在的药物相互作用。