Recent progress in the polysaccharides-prenylated flavonoids nanocomplexes

Polysaccharides are natural nano-carrier of prenylated flavonoids. Prenylated flavonoids are a unique group characterized by prenyl side chain on the flavonoid skeleton. The pentenylation can enhance the bioactivity and bioaccumulation of the parent flavonoids. The application of prenylated flavonoids as nutraceutical ingredients in functional foods has attracted increasing research interest. However, the limited water solubility and suboptimal oral bioavailability of prenylated flavonoids have challenged their application in the functional food and pharmaceutical industries. In This prior studies, This successfully encapsulated icaritin (a typical prenylated flavonoid utilized as a nutraceutical in functional food and medicine) using pectin as a nanocarrier, indicating the potential of polysaccharides as an effective delivery system for prenylated flavonoids. However, it was not feasible to effectively encapsulate icariin (a glycosylated derivative of icaritin) within pectin under the same conditions, suggesting the presence of structure-encapsulation relationship in polysaccharides-based nanocomplexes loaded with prenylated flavonoids. Phenolic hydrogen plays a critical role for the activities of flavonoids. Whether phenolic hydrogen affect the formation of polysaccharides-prenylated flavonoids nanocomplexes remains unknown.

Therefore, three prenylated flavonoids – icaritin (ICT), icariin (ICA), and icariside I (ICS) – were encapsulated in chitosan (CS) using a pH-driven method. The influence of the structural characteristics of these prenylated flavonoids on their encapsulation efficiency and their interaction with CS was investigated. The results showed that ICT, ICA, and ICS were well encapsulated in CS with various linear structure. The electrostatic interactions and hydrogen bonds were the driving forces contributing to the formation of prenylated flavonoids-loaded CS nanocomplexes. However, the hydrophobic interactions were formed to maintaining the stability of the external structure of nanocomplexes. Nuclear magnetic resonance spectra revealed the intermolecular hydrogen bonds were formed between the 3-OH and 7-OH of ICT and the amines of CS, and might mainly contributed to the highest loading capacity of ICT (16.29%) with CS. Notably, when both 3-OH and 7-OH are substituted with sugar moieties, ICA exhibited weaker intermolecular hydrogen bond interactions with CS, resulting in a significantly lower loading capacity of 5.54% (Figure 1). These results indicated the importance of phenolic hydroxyl groups on the encapsulation capacities of prenylated flavonoids with CS. The study might reveal the structure-encapsulation relationship of polysaccharides-based nanocomplexes loaded with prenylated flavonoids. Furthermore, this work might provide valuable insights for selecting more suitable delivery carriers for flavonoids with diverse structures.

This work was conducted by Dr. WANG Jinping under the instructions by the corresponding author Pro. YANG Bao and Dr. WEN Lingrong. The work was generously funded by grants from the National Natural Science Foundation of China, the Youth Innovation Promotion Association of the Chinese Academy of Sciences, and Science and Technology Projects of Guangdong Province and Guangzhou City. The relevant papers have been published in Food Hydrocolloids. For further reading, please refer to https://doi.org/10.1016/j.foodhyd.2025.111523

Figure. Chitosan-prenylated flavonoids nanocomplexes and the dominant forces driving their formation.（Imaged by WEN et al）