Development of Paeonol Liposomes: Design, Optimization, in vitro and in vivo Evaluation

Abstract

Background Ulcerative colitis (UC) is one of the intractable diseases recognized by the World Health Organization, and paeonol has been proven to have therapeutic effects. However, the low solubility of paeonol limits its clinical application. To prepare and optimize paeonol liposome, study its absorption mechanism and the anti-inflammatory activity in vitro and in vivo, in order to provide experimental basis for the further development of paeonol into an anti-inflammatory drug in the future. Methods Paeonol loaded liposomes were prepared and optimized by thin film dispersion-ultrasonic method. The absorption mechanism of paeonol-loaded liposomes was studied by pharmacokinetics, in situ single-pass intestinal perfusion and Caco-2 cell monolayer model, the anti-inflammatory activity was studied in a mouse ulcerative model. Results Box-Behnken response surface methodology permits to screen the best formulations. The structural and morphological characterization showed that paeonol was entrapped inside the bilayer in liposomes. Pharmacokinetic studies found that the AUC 0-t of Pae-Lips was 2.78 times than that of paeonol suspension, indicating that Pae-Lips significantly improved the absorption of paeonol. In situ single intestinal perfusion and Caco-2 monolayer cell model results showed that paeonol was passively transported and absorbed, and was the substrate of P-gp, MRP2 and BCRP, and the Papp value of Pae-Lips was significantly higher than that of paeonol. In vitro and in vivo anti-inflammatory experiments showed that compared with paeonol, Pae-Lips exhibited excellent anti-inflammatory activity. Conclusion In this study, Pae-Lips were successfully prepared to improve the oral absorption of paeonol. Absorption may involve passive diffusion and efflux transporters. Moreover, Pae-Lips have excellent anti-inflammatory activity in vitro and in vivo, which preliminarily clarifies the feasibility of further development of Pae-Lips into oral anti-inflammatory drugs.

A Pharmacokinetic Study of Sixteen Major Bioactive Components of Jinshui-Huanxian Granules in Pulmonary Fibrosis Model and Control Rats Using Orbitrap Fusion Mass Spectrometry

“…Paeonol has a quick first-pass metabolism. However, in the PF model, the metabolism could be impacted, which could be a reason for the low bioavailability [ 23 , 24 , 25 , 26 ]. The T max of Ginsenoside Rb 2 was slightly increased in the PF model group.…”

Protective mechanism of Paeonol on central nervous system

“…Three efflux proteins, p-glycoprotein, multidrug resistance protein 2 and breast cancer resistance protein, are involved. However, the distribution of this liposome in brain tissue remains to be studied (Huang et al, 2022). In terms of molecular structure, the relationship between active groups and biomolecules has not been reported.…”

“…It can inhibit sirtuin 1 (SIRT1) and interleukin‐1β (IL‐1β) by inhibiting osteoarthritis, gouty arthritis and gout‐induced inflammation to achieve it (Chen et al, 2019; Chen, Guo, & Yang, 2022; Shang et al, 2022). Pae has been proved to significantly inhibit the polarization of M1 cells in ulcerative colitis and inhibit the proinflammatory factors interleukin 6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) to inhibit the activation of NF‐κB/MAPK signal pathway, promoting the recovery and stability of intestinal flora by improving metabolites as well (Huang et al, 2022; Zheng et al, 2022). Similarly, it regulates the NOD‐like receptor thermal protein domain‐associated protein 3 (NLRP3) inflammatory body and inhibits the polarization of M1 cells, thereby downregulating the expression of related inflammatory factors to improve acute pancreatitis (Yuan et al, 2022).…”

Natural-derived acetophenones: chemistry and pharmacological activities

“…Acetophenones discovered in some genera of Asteraceae have proven to contribute to the pertaining properties of the family species. Embarking on the attempt to explore the cytotoxic constituents of Eupatorium fortune, Chang et al isolated an acetophenone derivative, known as eupatofortunone (125) that was elucidated to contribute to the therapeutic values of the host plant [59]. 2-Hydroxy-4-methylacetophenone (126) [60] was also extracted during the process.…”