Effects of folate-chicory acid liposome on macrophage polarization and TLR4/NF-κB signaling pathway in ulcerative colitis mouse.

BACKGROUND: Chichoric acid (CA) is a major active ingredient found in chicory and Echinacea. As a derivative of caffeic acid, it has various pharmacological effects. PURPOSE: Due to the unclear etiology and disease mechanisms, effective treatment methods for ulcerative colitis (UC) are currently lacking. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and dextran sulfate sodium (DSS)-induced mouse UC models. METHODS: Folate-chicory acid liposome was prepared using the double emulsion ultrasonic method with the aim of targeting folate receptors specifically expressed on macrophages. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and DSS -induced mouse UC models. Furthermore, the effects of the liposomes on macrophage polarization and their underlying mechanisms in UC were explored. RESULTS: The average particle size of folate-chicory acid liposome was 120.4 ± 0.46 nm, with an encapsulation efficiency of 77.32 ± 3.19 %. The folate-chicory acid liposome could alleviate macrophage apoptosis induced by LPS, decrease the expression of inflammatory factors in macrophages, enhance the expression of anti-inflammatory factors, inhibit macrophage polarization towards the M1 phenotype, and mitigate cellular inflammation in vetro. In vivo test, folate-chicory acid liposome could attenuate clinical symptoms, increased colon length, reduced DAI scores, CMDI scores, and alleviated the severity of colonic histopathological damage in UC mice. Furthermore, it inhibited the polarization of macrophages towards the M1 phenotype in the colon and downregulated the TLR4/NF-κB signaling pathway, thereby ameliorating UC in mice. CONCLUSION: Folate-chicory acid liposome exhibited a uniform particle size distribution and high encapsulation efficiency. It effectively treated UC mice by inhibiting the polarization of macrophages towards the M1 phenotype in the colon and downregulating the TLR4/NF-κB signaling pathway.

Effects of Ban Lian Zi Jin San on intestinal inflammation and barrier function of heat-stressed broilers.

Heat stress (HS) in broilers can be an environmental stressor that leads to intestinal inflammation and intestinal barrier damage. In order to examine the effect of Ban Lian Zi Jin San (BLZJS) on intestinal inflammation and barrier function in heat-stressed broilers, a model of chronic cyclic HS in broilers was established. A total of 300 twenty-one-day-old broilers were divided into 5 treatments at random. Broilers in 3 BLZJS dosage groups were kept in an ecologically controlled room at 37℃ ± 2℃ for 6 wk, and fed basal diets supplemented with 0.5, 1, and 2% BLZJS. Broilers in HS group were housed in the same room, but fed the basal diets. The findings indicated that supplementation of BLZJS significantly declined serum HS indexes levels (HSP70, HSP90), and increased serum antioxidant capacity (SOD and T-AOC) in broilers (P < 0.05). Besides, supplementation of BLZJS significantly inhibited the expression of HS indexes (HSP70 and HSP90), genes related to TLR4 inflammatory signal pathway (TLR4, MyD88, TRIF, IRAK-4, and NF-κB), inflammatory factors (IL-6 and TNF-α), and upregulated anti-inflammatory cytokines (IL-10) and intestinal tight junction-related genes (Occludin, Claudin-1, and ZO-1) in broiler jejunum (P < 0.05). On the other hand, supplementation of BLZJS could significantly reduce the protein expression of NF-κB and HSP70 in chick jejunum (P < 0.05). In conclusion, BLZJS inhibited the activation of TLR4 signal pathway and reduced the production of inflammatory factors, restoring the level of intestinal tight junction protein and protecting jejunal intestinal barrier function in heat-stressed broilers.

The mixture of Radix isatidis, Forsythiae, and Gypsum alleviates lipopolysaccharide-induced fever in broilers by inhibition of TLR4/NF-κB signaling pathway.

To determine whether the antipyretic effect of the mixture of Radix isatidis, Forsythiae, and Gypsum (RIFG) on lipopolysaccharide (LPS) induced fever broilers and its related mechanisms. A total of 315 24-day-old yellow-plumed broilers were randomly divided into 7 groups, except for the control group, other groups were injected with LPS. Two hours later, RIFG were given drinking water to relieve fever, and it was evaluated by the expression of genes and proteins of the maximum body temperature rise (∆T), body temperature response index (TRI), serum and hypothalamic pyrogenic heat factor. RIFG could reduce the body temperature of broilers with fever (P < 0.01). It inhibited the expressions of IL-6 and PGE2 (P < 0.01), down-regulated mRNA expression levels of TNF-ɑ and COX-2 (P < 0.01), and promoted the generation of antipyretic factor AVP mRNA (P < 0.01). In addition, the expression level of TLR4 and NF-κB p65 protein can be down-regulated, and LPS + RM group has the best down-regulated effect. RIFG had a good antipyretic effect on reducing LPS-induced fever of broilers by inhibiting the activation of TLR4/NF-κB signaling pathway and thermogenic factors.

Echinacea purpurea (L.) Moench Polysaccharide Alleviates DSS-Induced Colitis in Rats by Restoring Th17/Treg Balance and Regulating Intestinal Flora.

Echinacea purpurea is popularly used as a food supplement or nutritional supplement for its immune regulatory function against various threats. As one of its promising components, Echinacea purpurea (L.) Moench polysaccharide (EPP) has a wide range of biological activities. To evaluate the effect of EPP as a dietary supplement on ulcerative colitis (UC), this study used sodium dextran sulfate (DSS) to induce a UC model, extracted EPP using the ethanol subsiding method, and then supplemented with EPP by gavage for 7 days. Then, we evaluated the efficacy of EPP on DSS rats in terms of immunity, anti-inflammation, and intestinal flora. The result showed that EPP could alleviate colonic shortening and intestinal injury in rats with DSS-induced colitis, decrease the disease activity index (DAI) score, downregulate serum levels of inflammatory cytokines, and contribute to the restoration of the balance between the T helper cells 17 (Th17) and the regulatory T cells (Treg) in the spleen and mesenteric lymph nodes (MLNs). Meanwhile, EPP could downregulate the expression of Toll-like receptors 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-B (NF-κB) in colon tissue. In addition, the results of 16SrRNA sequencing showed that EPP also had a regulatory effect on intestinal flora of UC rats. These results indicate that EPP might achieve a beneficial effect on UC rats as a dietary supplement through restoring Th17/Treg balance, inhibiting the TLR4 signaling pathway and regulating intestinal flora, suggesting its possible application as a potential functional food ingredient alleviating UC.