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https://doi.org/10.1016/j.jep.2021.114336
Received 25 January 2021; Received in revised form 2 June 2021; Accepted 11 June 2021
ABSTRACT
Ethnopharmacological relevance: Viticis fructus (VF) has been widely used in alleviating the swelling and pain, owning to its pharmacologically active components including agnuside,10-O-vanilloylaucubin, luteolin and casticin.
Aim of the study: The pharmacokinetic profiles of the absorbed components from aqueous and ethanolic ex-tracts of VF in rat plasma were performed, and explored the molecular mechanisms of absorbed components via network pharmacology.
Materials and methods: Ultra-performance liquid chromatography-tandem mass spectroscopy (UHPLC-MS/MS)was employed to identify the absorbed components from rat plasma. Liquid-liquid extraction with ethyl acetate was used to purify the plasma samples. Plasma pharmacokinetics parameters of the components absorbed were analyzed after oral administration of both extracts. Network pharmacology was used to predict the biological functions and potential signaling pathways of VF. The anti-cancer effects of VF extract and absorbed components have been confirmed by in vitro experiments.
Results: The method was very sensitive with lower limit of quantification (LLOQ) of 1.0, 2.5, 0.2 and 0.5 ng/mL for agnuside, 10-O-vanilloylaucubin, luteolin and casticin, respectively. With the exception of 10-O-vanil-loylaucubin which was not detected in the ethanolic extract of VF, all other components were detected in both extracts in plasma. The pharmacokinetic parameters of the four components from rat plasma were significantly different between the two extracts. According to the results of network pharmacology, the absorption compo-nents of VF are enriched in 32 key pathways, and 15 pathways are related to cancer. Ultimately, the anti-cancer effects, as well as the signaling pathways of VF ethanolic extract and absorbed components were veri-fied by in vitro experiments.
Conclusion: The optimized, sensitive and validated UHPLC-MS/MS method was successfully applied for the plasma pharmacokinetics comparison analysis of the two VF extracts. The combination of network pharma-cology and pharmacokinetics provides a useful method to elucidate the biological effects and molecular mechanism of the absorbed components of VF.
laboratory. Agnuside, luteolin, casticin, formononetin and geniposide (purity on HPLC> 98%) were supplied by Chengdu Desite Bio-Technology (Chengdu, China).
Structure
