Wedelolactone induces natural killer cell activity and the improvement to bioavailability using polysaccharides from Ligustri Lucidi Fructus

Wedelolactone (WDL) is the major bioactive component in Ecliptae Herba. This present study investigated the effects of WDL on natural killer cell functions and possible underlying mechanisms. It was proved that wedelolactone enhanced the killing ability of NK92-MI by upregulating the expression of perforin and granzyme B through the JAK/STAT signaling pathway. Additionally, wedelolactone could induce the migration of NK-92MI cells by promoting CCR7 and CXCR4 expressions. However, the application of WDL is limited due to poor solubility and bioavailability. Accordingly, this study investigated the impact of polysaccharides from Ligustri Lucidi Fructus (LLFPs) on WDL. The biopharmaceutical properties and pharmacokinetic characteristics were determined to compare WDL individually and in combination with LLFPs. The results showed that LLFPs could benefit the biopharmaceutical properties of WDL. Specifically, stability, solubility, and permeability were increased by 1.19-1.82-fold, 3.22-fold, and 1.08-fold higher than those of WDL alone, respectively. Furthermore, the pharmacokinetic study revealed that LLFPs could remarkably improve AUC(0-t) (150.34 vs. 50.47 ng/mL * h), t1/2 (40.78 vs. 2.81 h), and MRT(0-& INFIN;) (46.64 vs. 5.05 h) for WDL. In conclusion, WDL would be considered a potential immunopotentiator, and LLFPs could overcome the instability and insolubility, ultimately improving the bioavailability of this plant-derived phenolic coumestan.

Automated summary

This study demonstrated that Wedelolactone (WDL) enhanced the killing ability of NK92-MI cells by upregulating the expression of perforin and granzyme B through the JAK/STAT signaling pathway. Additionally, WDL induced the migration of NK-92MI cells by promoting CCR7 and CXCR4 expressions. However, the application of WDL is limited due to poor solubility and bioavailability. Therefore, Ligustri Lucidi Fructus polysaccharides (LLFPs) were investigated for their impact on WDL, which improved its biopharmaceutical properties and pharmacokinetic characteristics, ultimately enhancing its bioavailability.