Effects of solid lipid ratio in curcumin loaded emulsions on its gastrointestinal fate: Colloidal stability and mucus absorption efficiency.

Emulsions offer a promising approach for enhancing the bioavailability of lipophilic active compounds when administered orally. Nonetheless, the impact of lipid matrix composition on the efficacy of penetration and bioavailability remains uncertain. This research investigated the effects of solid lipid ratio in emulsions on colloidal stability, mucus permeability, and bioavailability in vivo. To assess colloidal stability in the gastrointestinal tract (GIT), Turbiscan was employed. The results indicated that an elevated solid lipid ratio improved intestinal stability through the formation of aggregations that resisted pancreatic absorption, as confirmed by TEM. The absorption in various intestinal sections was tested using the Ussing Chamber model. Notably, emulsion with 0 % solid lipid (G0M10) exhibited the highest cumulative permeation across the duodenum (221.2 ± 21.19 ng), jejunum (713.1 ± 20.93 ng), and ileum (1056.3 ± 392.06 ng) due to its higher in vitro release rate (>60 %) and smaller particle size. The cumulative permeation decreased with increasing solid lipid ratio. CLSM revealed that emulsions with a solid lipid ratio exceeding 50 % exhibited poor mucus permeability within 15 min due to aggregation during the passage in the GIT. However, over an extended penetration time (30 min), higher permeability was observed, reaching approximately 30 µm. In vitro release studies indicated that a higher solid lipid ratio resulted in a reduced release rate of curcumin (<60 %) compared to G0M10 (66.9 ± 3.58 %). Correlation analysis unveiled a positive link between bioavailability and in vitro release rate, while a negative correlation emerged with the solid lipid ratio. This work underscores the significance of solid lipid ratios in emulsions for optimizing bioavailability through their influence on stability, permeability, and release of lipophilic compounds in the GIT.

Rosmarinic Acid Restores Colonic Mucus Secretion in Colitis Mice by Regulating Gut Microbiota-Derived Metabolites and the Activation of Inflammasomes.

Maintaining a steady state of mucus barrier is an important potential target for polyphenol to exert its anticolitis activity. This study elucidates the pivotal role of polyphenol rosmaric acid (RA) in regulating the mucus barrier function and alleviating inflammation by identifying its gut microbiota-derived metabolites and evaluating its inhibitory effect on inflammasomes in colitis mice. Results demonstrated that RA treatment promoted the proliferation of goblet cells and restored the level of mucus secretion, especially Muc2. RA reshaped the microbiota of colitis mice, particularly the boost of core probiotics, such as p. Bacteroidaceae, f. Muribaculaceae, g. Muribaculaceae, g. Alistipes, and g. Clostridia_UCG-014. Nontargeted metabonomics and targeted metabonomics confirmed a significant increase in the bile acids and their metabolites (7-sulfocholic acid, stercobilin, chenodeoxycholic acid 3-sulfate, chenodeoxycholic acid sulfate, and ursodeoxycholic acid 3-sulfate), indole metabolites ((R)-2,3-dihydro-3,5-dihydroxy-2-oxo-3-indoleacetic acid, frovatriptan, 3-formyl-6-hydroxyindole, and brassicanal A), and short-chain fatty acids (SCFAs) (acetic acid, butyric acid, isobutyric acid, isovaleric acid, and valeric acid) that contributed to the strengthened mucus barrier function. In addition, being absorbed mainly in the lower digestive tract, RA inhibited the overexpression of inflammasomes (especially NLRP6) that occurred in colitis mice to promote the mucus secretion of goblet cells. These data confirmed that RA, as a promising candidate to enhance gut health, restored colonic mucus secretion in colitis mice by mediating the production of gut microbiota-derived metabolites and the overexpression of inflammasomes. The presented study provides scientific evidence explaining the apparent paradox of low bioavailability and high bioactivity in polyphenols.

Hydroxytyrosol Alleviates Dextran Sulfate Sodium-Induced Colitis by Modulating Inflammatory Responses, Intestinal Barrier, and Microbiome.

Hydroxytyrosol (HT), a polyphenol derived from olive oil, was examined against dextran sulfate sodium (DSS)-induced colitis to study its potential in preventing colitis and the underlying mechanisms involved. The low dose and high dose of HT used in mice were 10 and 50 mg/kg, respectively. Research findings have shown that HT is effective in preventing colitis by alleviating the signs of colitis. HT intervention significantly reduces colitis markers such as myeloperoxidase (MPO) and proinflammatory cytokine (IL-6, IL-1ß, and TNF-α). Also, mice treated with a high dose of HT showed increased secretion of antioxidant enzymes (heme oxygenase-1 (HO) and anti-inflammatory cytokine (IL-10) by 2.32- and 2.28-fold, respectively, in comparison to the DSS-treated group. Modulation effects of HT on the antioxidant signal pathway (NRF2) and the inflammatory pathway (NF-κB) were confirmed. Meanwhile, HT promoted the regeneration of the intestinal barrier and maintained intestinal functional homeostasis by boosting the regeneration of goblet cells and the expression of mucin protein (Muc2) and tight junction (TJ) proteins (claudin-1, occludin, and Zonula Occludens-1). Moreover, HT intervention obviously transformed the gut microbiota, leading to a lower abundance of inflammation-related microbes (e.g., Bacteroidaceae and Desulfovibrionaceae) and a higher level of short-chain fatty acids (SCFAs) producing bacteria (e.g., Lachnospiraceae, Muribaculaceae, ASF356, and Colidextribacter). Scientific evidence for the beneficial effect of the "Mediterranean diet" (MD) on intestinal health was achieved by elucidating the alleviation mechanism of hydroxytyrosol on colitis.