Bulbine natalensis, an emerging medicinal herb on the global market with androgenic properties, is often formulated in dietary supplements that promote perceived sexual enhancement. However, to date, comprehensive safety studies of B. natalensis are lacking, particularly those related to its herb-drug interaction potential. The purpose of this study was to assess the inductive and inhibitory effects of extracts and pure compounds of B. natalensis on human cytochrome P-450 isozymes in vitro. Our findings demonstrated that both water and methanolic extracts of B. natalensis as well as knipholone, bulbine-knipholone, and 6′-O-methylknipholone dose-dependently increased mRNA expression encoded by CYP2B6, CYP1A2, and ABCB1 genes. Functional analyses showed that water (60 to 2.20 µg/mL) and methanolic (30 to 3.75 µg/mL) extracts and knipholones (10 to 0.33 µM) increased CYP2B6 and CYP1A2 activity in a dose-dependent manner. Additionally, water extract (60 µg/mL), methanolic extract (30 µg/mL), and knipholone (10 µM) caused activation of the aryl hydrocarbon receptor up to 11.1 ± 0.7, 8.9 ± 0.6, and 7.1 ± 2.0-fold, respectively. Furthermore, inhibition studies revealed that methanolic extract attenuated the activity of metabolically active CYP1A2 (IC50, 22.6 ± 0.4 µg/mL) and CYP2B6 (IC50, 34.2 ± 6.6 µg/mL) proteins, whereas water extracts had no inhibitory effect on either isoform. These findings suggest that chronic consumption of B. natalensis may affect normal homeostasis of select CYPs with subsequent risks for HDIs when concomitantly ingested with conventional medications that are substrates of CYP2B6 and CYP1A2. However, more in-depth translational studies are required to validate our current findings and their clinical relevance.

中文翻译：

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Bulbine natalensis（目前 Bulbine latifolia）和精选的bulbine knipholones 调节 AhR、CYP1A2、CYP2B6 和 P-gp 的活性

Bulbine natalensis 是全球市场上一种新兴的具有雄激素特性的药草，通常用于膳食补充剂中，以促进感知性增强。然而，迄今为止，缺乏对 B. natalensis 的全面安全性研究，特别是那些与其草药-药物相互作用潜力相关的研究。本研究的目的是评估 B. natalensis 提取物和纯化合物在体外对人细胞色素 P-450 同工酶的诱导和抑制作用。我们的研究结果表明，B. natalensis 的水和甲醇提取物以及 knipholone、bulbin-knipholone 和 6'-O-methylknipholone 剂量依赖性地增加由 CYP2B6、CYP1A2 和 ABCB1 基因编码的 mRNA 表达。功能分析表明，水（60 到 2.20 µg/mL）和甲醇（30 到 3.75 µg/mL）提取物和克尼福龙（10 到 0. 33 µM) 以剂量依赖性方式增加 CYP2B6 和 CYP1A2 活性。此外，水提取物 (60 µg/mL)、甲醇提取物 (30 µg/mL) 和克尼佛龙 (10 µM) 导致芳烃受体活化高达 11.1 ± 0.7、8.9 ± 0.6 和 7.1 ± 2.0 倍，分别。此外，抑制研究表明，甲醇提取物减弱了具有代谢活性的 CYP1A2 (IC50, 22.6 ± 0.4 µg/mL) 和 CYP2B6 (IC50, 34.2 ± 6.6 µg/mL) 蛋白质的活性，而水提取物对这两种异构体都没有抑制作用。这些研究结果表明，当与作为 CYP2B6 和 CYP1A2 底物的常规药物同时摄入时，长期食用 B. natalensis 可能会影响选定 CYP 的正常体内平衡，从而导致 HDIs 的风险。然而，