Self-assembled Nano Delivery System of Fenugreek Polysaccharides: Effects on Curcumin Bioavailability and Molecular Mechanisms

Self-assembly of fenugreek polysaccharides FS60 (a natural macromolecular material) with curcuminoid has been proved to improve curcumin (Cur) water dispersion in preliminary studies. This study further explored the effect of FS60 on Cur bioavailability in vivo to assess the significance of this delivery method. In this study, we optimized the formulation parameters of FS60–curcuminoid aggregates (FC) and studied their effects on Cur pharmacokinetics in rats. Results showed that the optimized aggregates had an encapsulation efficiency (EE) of 88.22 % and hydrodynamic diameter (DH) of 231.48 nm. Additionally, administering FC significantly increased curcumin glucuronide (Cur-O-Glu) levels. The Cmax was 51 times higher and AUC0–12h was 19 times higher than curcuminoid alone. Moreover, FS60 intervention for seven days increased the absorption speed of Cur-O-Glu into the bloodstream. Further mechanistic studies indicated that FS60 promoted Cur ingestion, increased UGT expression, and inhibited enterocyte transporters, allowing large amounts of Cur-O-Glu to enter the bloodstream. Moreover, the gut microbiota modulated by FS60 accelerated the mutual conversion of pentose and gluconate to provide sufficient glucuronic acid for the glucuronidation of Cur in enterocytes. Consequently, the nano delivery system composed by FS60 and curcuminoid facilitated gastrointestinal Cur glucuronidation and Cur-O-Glu absorption.