Effect of folic acid-Echinacea-derived alkylamides liposomes on mice with ulcerative colitis

Background and Purpose: Alkylamides (AADs) are lipophilic bioactive compounds found in plants of the families Asteraceae, Aristolochiaceae, Piperaceae, and others. It has demonstrated significant efficacy in reducing inflammation and modulating immune responses, establishing it as a promising therapeutic agent for ulcerative colitis (UC). We investigated the efficacy of AADs and folic acid-alkylamide liposomes (FAL) on macrophage inflammation and a mouse model of UC. Methods: AAds were extracted from the roots of Echinacea purpurea by methanol, petroleum ether extraction and silica gel column chromatography. The FAL were prepared by ethanol injection method and characterized by high performance liquid chromatography and scanning electron microscopy, and low speed centrifugation was used to determine the encapsulation rate and drug loading capacity of FAL, as well as to determine the stability and the rate of release, to assess the characterization of FAL. And its efficacy was relevantly validated using cellular and animal models. Results: AADs were isolated from Echinacea purpurea roots, and FAL was prepared, yielding uniformly spherical particles (122.7 ± 0.4 nm) with a high encapsulation efficiency (85.72 ± 2.48%) and drug loading (4.54 ± 0.12%). FAL suppressed the M1 macrophage markers (TNF-α, IL-6, and CD86) in RAW264.7 cells while elevating the expression of M2 markers (IL-10 and Arg-1). In vivo, FAL lowered the disease activity index and colon index in UC mice, increased colon length, and mitigated histopathological damage. Furthermore, FAL modulated cytokine levels in serum and colon tissue, downregulated the NF-κB/JAK2/STAT3 pathway, and activated the Nrf2/HO-1 axis. Conclusion: FAL particles are small and uniform, exhibiting high encapsulation efficiency. They ameliorate colonic inflammation in mice by suppressing macrophage polarization toward the M1 phenotype while promoting M2 polarization. This formulation also modulates the Nrf2/HO-1 and JAK2/STAT3/NF-κB signaling pathways, thereby reducing inflammatory cytokine levels in the mouse colon and alleviating ulcerative colitis.