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September 10, 2025Open Access

The pharmacokinetics effects of the MCAO model on senkyunolide I in pseudo germ-free rats after oral co-administration of Chuanxiong and warfarin

Key Points

The MCAO operation significantly altered the pharmacokinetics of senkyunolide I following oral administration.
Increased AUC and C max were observed in the WC group, indicating enhanced absorption of senkyunolide I in MCAO rats.
The pharmacokinetics of warfarin were also influenced by the pseudo germ-free condition and MCAO operation.
Understanding these changes may provide insights into how gut microbiota affects herb-drug interactions.

Abstract

Aim To investigate the pharmacokinetics effects of a middle cerebral artery occlusion (MCAO) model on senkyunolide I (SEI) in pseudo germ-free rats after oral co-administration of Chuanxiong and warfarin. Methods Rats were divided randomly into WCH, WSH, WCHF, WSHF, WC, WS, WCF, and WSF groups (W, warfarin; C, Chuanxiong; S, SEI; H, rats without an MCAO operation; F, pseudo germ-free). Pseudo germ-free rats were orally administered ciprofloxacin hydrochloride (50 mg/kg, twice a day) for 3 consecutive days, and the MCAO operation was carried out on the third day. Chuanxiong (10 g/kg) or SEI (7. 5 mg/kg) and warfarin sodium (0. 5 mg/kg) were orally administered only once on the fourth day. The plasma concentrations of SEI were determined by UPLC-MS/MS. Stool samples were collected for gut microbiota analyses. The coronal thin slices of the brain were dyed with triphenyl-2H-tetrazolium chloride. Results Compared to the WCH group, the AUC 0-t and C max of the WC group increased 2. 08- and 1. 79-fold (P 0. 001), respectively. Compared with the WSH group, the AUC 0-t and C max of the WS group decreased by 6. 24% and 22. 64% (P 0. 001), respectively. Compared to the WCHF group, the AUC 0-t and t 1/2z of the WCF group decreased by 60. 95% and 35. 26% (P 0. 01), respectively. Compared with the WSHF group, the AUC 0-t and C max of the WSF group decreased by 2. 87% and 8. 54% (P 0. 001), respectively. Compared to the WCH group, the AUC 0-t and C max of the WCHF group increased by 85. 03% and 82. 48% (P 0. 001), respectively. Compared with the WSH group, the AUC 0-t and C max of the WSHF group increased 1. 40-and 2. 43-fold (P 0. 001), respectively. Compared to the WC group, the AUC 0-t and t 1/2z of the WCF group decreased by 45. 81% and 79. 44% (P 0. 001), respectively. Compared with the WS group, the AUC 0-t and t 1/2z of the WSF group decreased by 35. 86% and 79. 74% (P 0. 001), respectively. Conclusion Both the MCAO operation and the pseudo germ-free condition significantly changed the pharmacokinetics characteristics of SEI after oral co-administration with warfarin and Chuanxiong or SEI. It is a promising way to understand the potential pharmacokinetics of herb–drug interactions from the angle of the gut microbiota.

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