Active components unveiling and pharmacodynamic research on Valeriana jatamansi jones for ameliorating ulcerative colitis based on pharmacokinetics and network pharmacology.

Ethnopharmacological Relevance: Valeriana jatamansi Jones (V. jatamansi), a traditional Chinese medicine, is widely used in the treatment of gastrointestinal disorders, such as ulcerative colitis (UC). However, the active components of V. jatamansi with protective effect on the intestinal barrier remains elusive.

Aim Of The Study: This investigation was conducted to confirm the efficacy of V. jatamansi ethanol extract for the treatment of UC and to identify the active compounds in ethanol extract of V. jatamansi that have a protective effect against intestinal barrier damage.

Materials And Methods: The role of V. jatamansi extract was assessed on dextrose sodium sulfate (DSS) induced colitis in vivo. The wound healing, apoptosis and epithelial barrier permeability of intestinal epithelial cells (NCM460 cells) were evaluated in vitro. UHPLC-MS method was used to determine the pharmacokinetic characteristics of V. jatamansi extract after oral administration. The effect of absorbed compounds on the intestinal barrier was assessed on NCM460 cells. Fuzzy matter-element analysis was used to explore the main compounds, and the results were verified by FITC-dextran assay. Network pharmacology was used to predict the potential mechanisms and western blotting was used to validate the results.

Results: The ethanol extract ofV. jatamansi relieves symptoms, inflammatory response and intestinal barrier damage in DSS-induced UC. It effectively alleviated DSS-induced epithelial barrier damage in NCM460 cells. Pharmacokinetic analyses indicated that the five components (chlorogenic acid, hesperidin, valerosidate, isochlorogenic acid B and cryptochlorogenic acid) were quickly absorbed into the blood after oral administration of ethanol extract. The fuzzy matter-element analysis and FITC-dextran assay demonstrated that valerosidate and chlorogenic acid played an important role in the protection of the intestinal barrier damage. Network pharmacological analyses and western blotting analyses showed that the ethanol extract of and absorbed components significantly inhibited the Bcl-2/Bax/Caspase-3 signaling pathway, and suppressed DSS-induced apoptosis in NCM460 cells.

Conclusion: The ethanol extract of V. jatamansi ameliorates intestinal barrier injury in UC mice through multi-components. Valerosidate and chlorogenic acid were identified as anti-colitis compounds. These provided new insights into finding the active components for the treatment of UC and contribute to the clinical application of V. jatamansi.