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Wang, Dongpeng; Duan, Jufeng; Chen, Xiao-Jing; Liu, Kaiqi; Guo, Yingying; Shi, Run; Li, Sha; Liu, Ming; Zhao, Lijun; Li, Bei; Liu, Hongtao; Li, Minglun; Feng, Yibin; Li, Hongliang and Wang, Xuanbin (2022): Pharmacokinetic characteristics of emodin in polygoni Multiflori Radix Praeparata. In: Journal of Ethnopharmacology, Vol. 303, 115945

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Ethnopharmacological relevance: Polygoni Multiflori Radix Praeparata (Zhiheshouwu) has been a Wudang Taoist medicine for tonifying the liver and kidney, resolving turbidity and reducing lipid. Emodin is one of the active anthraquinones in Zhiheshouwu. Our previous studies showed that emodin (EM) and the other anthraquinones in Zhiheshouwu extract (HSWE) exerted similar inhibitory effects on liver cancer cells in vitro. However, it is still unknown if the other anthraquinones enhance pharmacokinetics (PK) of EM in HSWE in vivo.Aim of the study: In this study, we compared the PK characteristics of EM alone with that in Zhiheshouwu aiming to explore which anthraquinones in HSWE contribute to the changed PK of EM in rats.Materials and methods: Quality control of HSWE was determined using high performance liquid chromatography (HPLC). The ratios of emodin to other anthraquinones, physcion (PH), chrysophanol (CH), rhein (RH), aloe-emodin (AE), emodin-8-O-beta-D-glycoside (EMG), physcion-1-O-beta-D-glycoside (PHG) and chrysophanol-8-O-beta-D-glycoside (CHG) in HSWE were determined and analyzed using UPLC combined with tandem mass spectrometry (UPLC/MS). The PK parameters and intestinal tissue concentration of EM alone, EM in HSWE, or with other anthraquinones in SD rats were analyzed using UPLC/MS.Results: The quality of the Zhiheshouwu samples met the quality standard of the Chinese Pharmacopoeia (Version 2020). The PK results showed that compared with EM alone, Cmax (239.90 +/- 146.71 vs. 898.46 +/- 291.62, P < 0.001), Tmax (0.26 +/- 0.15 vs. 12.55 +/- 1.33, P < 0.001), AUC0-t (1575.09 +/- 570.46 vs. 12154.96 +/- 5394.25, P < 0.001), and AUC0-infinity (4742.51 +/- 1837.62 vs. 37131.34 +/- 21647.39, P < 0.001) of EM in HSWE were decreased due to PH and EMG, while the values of Vd (380.75 +/- 217.74 vs. 11.75 +/- 7.35, P < 0.001), T1/2 (10.81 +/- 1.99 vs. 6.65 +/- 2.76, P < 0.05) and CL (19.30 +/- 7.82 vs. 2.78 +/- 1.88, P < 0.001) of EM in HSWE were increased due to PH and AE. In addition, the intestinal tissue concentration of emodin in HSWE was decreased compared with that of EM alone in 20 and 780 min (25.37 +/- 5.98 vs. 43.29 +/- 4.16 and 26.72 +/- 4.03 vs. 43.40 +/- 14.19, respectively. P < 0.05) dominantly due to RH and PH.Conclusion: In conclusion, compared with treatment of EM alone, the AUC0-t value of EM in HSWE was decreased with different ways in rats. PH shortened Tmax, and increased Vd and CL. While AE prolonged T1/2 of EM. This indicated that the other anthraquinones in HSWE changed the PK of EM in rats and participated in the complex effects of EM on liver cancer. Besides the other anthraquinones, other components (e.g., 2,3,5,4 '-tetrahydrox-ystilbene-2-O-/3-D-glucoside) in Zhiheshouwu may contribute in the pharmacokinetic and pharmacodynamic interactions with EM for anti-liver cancer.

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