Department of Pharmaceutical Analysis, Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Department of Pharmacology, School of Life Sciences and Biopharmaceutical, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Food Funct. 2022 Jul 4;13(13):7098-7111. doi: 10.1039/d2fo00521b.
Cholestasis is a common liver injury without any effective therapeutic drugs so far. Resveratrol (RES) and luteolin (LUT) are natural polyphenols that exert protective effects on multiple liver injuries. Coadministration of RES and LUT could significantly improve the bioavailability of LUT and increase the systemic exposure to RES, and the combined treatment could also benefit from their multi-component and multi-target characteristics. Our current aim is to study the protective effects of coadministration of RES and LUT on α-naphthylisothiocyanate (ANIT)-induced cholestasis. Serum biochemical indices and liver histopathology in rats indicated that coadministration of RES and LUT could improve liver function by suppressing oxidative stress. Dysregulated bile acid (BA) homeostasis is a significant pathological feature of cholestasis, which was determined to explore the potential biomarkers and to clarify the protection mechanism of coadministration of RES and LUT. The levels of cholic acid, chenodeoxycholic acid, taurine conjugates and glycine conjugates, and the ratios of taurine conjugates to their free forms could be used as diagnosis indicators for cholestasis in rats. Furthermore, the coadministration of RES and LUT could restore the BA levels and exert better protective effects than administration alone. This study suggested that the coadministration of RES and LUT could protect against ANIT-induced cholestasis and the mechanism was closely related to regulating BA homeostasis and suppressing oxidative stress.
胆汁淤积是一种常见的肝脏损伤，目前尚无有效的治疗药物。白藜芦醇（RES）和木犀草素（LUT）是天然多酚类化合物，对多种肝损伤具有保护作用。RES 和 LUT 的联合给药可以显著提高 LUT 的生物利用度并增加 RES 的全身暴露，联合治疗还可以受益于它们的多组分和多靶点特性。我们目前的目的是研究 RES 和 LUT 联合给药对α-萘异硫氰酸酯（ANIT）诱导的胆汁淤积的保护作用。大鼠血清生化指标和肝组织病理学表明，RES 和 LUT 的联合给药通过抑制氧化应激改善肝功能。胆汁酸（BA）稳态失调是胆汁淤积的一个重要病理特征，我们旨在确定潜在的生物标志物并阐明 RES 和 LUT 联合给药的保护机制。胆酸、鹅脱氧胆酸、牛磺酸缀合物和甘氨酸缀合物的水平以及牛磺酸缀合物与其游离形式的比值可作为大鼠胆汁淤积的诊断指标。此外，RES 和 LUT 的联合给药可以恢复 BA 水平，并比单独给药具有更好的保护作用。本研究表明，RES 和 LUT 的联合给药可以预防 ANIT 诱导的胆汁淤积，其机制与调节 BA 稳态和抑制氧化应激密切相关。
