Vanillin is a popular flavoring agent in the food, tobacco, and perfume industries. In this paper, we investigated the effect of vanillin on the transport rates of drugs with different levels of permeability (acyclovir, hydrochlorothiazide, propranolol and carbamazepine) through a Caco-2 cell bidirectional transport experiment. We also explored the underlying mechanism using an in silico technique and fluorescence anisotropy measurements. The influence of vanillin on the pharmacokinetics of drugs whose transport rates were affected by vanillin in vitro was then studied in vivo. Results showed that vanillin (100 μM) increased the cumulative amount of passively transported drugs (2.1-fold of hydrochlorothiazide, 1.49-fold of propranolol, 1.35-fold of acyclovir, and 1.34-fold of carbamazepine) in vitro. Molecular dynamics simulations revealed that vanillin disordered the structure of the lipid bilayer and reduced the energy barrier of drugs across the center of the membrane. The anisotropy of TMA-DPH also decreased in Caco-2 cells after treatment with vanillin (25 and 100 μM) and indicated an increase in membrane fluidity, which was dose-dependent. An oral bioavailability study indicated that vanillin (100 mg kg-1) significantly enhanced the Cmax and AUC0-6 of hydrochlorothiazide by 1.42-fold and 1.28-fold, respectively, and slightly elevated the Cmax of propranolol. In conclusion, vanillin can significantly increase the absorption of drugs with moderate oral bioavailability in vitro and in vivo by loosening the membrane. Thus, the concurrent consumption of drugs with food containing vanillin may result in increased drug plasma concentration and pose potential health risks.

中文翻译：

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香兰素通过影响膜结构，在体内外具有中等的口服生物利用度，从而提高了药物的被动转运速率和吸收率。

香兰素是食品，烟草和香水行业中流行的调味剂。在本文中，我们通过Caco-2细胞双向转运实验研究了香兰素对具有不同通透性水平的药物（阿昔洛韦，氢氯噻嗪，普萘洛尔和卡马西平）的转运速率的影响。我们还探索了使用计算机技术和荧光各向异性测量的潜在机制。然后在体内研究了香兰素对转运速率受香兰素影响的药物的药代动力学的影响。结果表明，香兰素（100μM）在体外增加了被动转运药物的累积量（氢氯噻嗪2.1倍，普萘洛尔1.49倍，阿昔洛韦1.35倍和卡马西平1.34倍）。分子动力学模拟表明，香兰素破坏了脂质双层的结构，并降低了跨膜中心的药物的能量屏障。香草醛（25和100μM）处理后，在Caco-2细胞中TMA-DPH的各向异性也降低，表明膜流动性增加，这是剂量依赖性的。口服生物利用度研究表明，香兰素（100 mg kg-1）显着提高氢氯噻嗪的Cmax和AUC0-6分别为1.42倍和1.28倍，并稍微提高心得安的Cmax。总之，香兰素可通过使膜变松而在体内外显着增加具有中等口服生物利用度的药物的吸收。因此，