rosmarinic-acid and Colitis

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.

Topics: Animals; Colitis; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Inflammasomes; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Mucus; Rosmarinic Acid

Ulcerative colitis (UC), one of the two main types of inflammatory bowel disease, has no effective treatment. Rosmarinic acid (RA) is a polyphenol that, when administered orally, is metabolised in the small intestine, compromising its beneficial effects. We used chitosan/nutriose-coated niosomes loaded with RA to protect RA from gastric degradation and target the colon and evaluated their effect on acute colitis induced by 4% dextran sodium sulphate (DSS) for seven days in mice. RA-loaded nanovesicles (5, 10 and 20 mg/kg) or free RA (20 mg/kg) were orally administered from three days prior to colitis induction and during days 1, 3, 5 and 7 of DSS administration. RA-loaded nanovesicles improved body weight loss and disease activity index as well as increased mucus production and decreased myeloperoxidase activity and TNF-α production. Moreover, RA-loaded nanovesicles downregulated protein expression of inflammasome components such as NLR family pyrin domain-containing 3 (NLRP3), adaptor protein (ASC) and caspase-1, and the consequent reduction of IL-1β levels. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expression increased after the RA-loaded nanovesicles treatment However, these mechanistic changes were not detected with the RA-free treatment. Our findings suggest that the use of chitosan/nutriose-coated niosomes to increase RA local bioavailability could be a promising nutraceutical strategy for oral colon-targeted UC therapy.

Topics: Animals; Cinnamates; Colitis; Depsides; Disease Models, Animal; Heme Oxygenase-1; In Vitro Techniques; Inflammasomes; Inflammation; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Nanomedicine; Nanoparticles; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Peroxidase; Rosmarinic Acid; Signal Transduction; Tumor Necrosis Factor-alpha

Rosmarinic acid (RA), one of the most important polyphenol-based antioxidants, has received growing interest because of its bioactive properties, including anti-inflammatory, anticancer, and antibacterial activities. Despite the high therapeutic potential of RA, its intrinsic properties of poor water solubility and low bioavailability have limited its translation into the clinic. Here, we report on the synthesis and preparation of PEGylated RA-derived nanoparticles (RANPs) and their use as a therapeutic nanomedicine for treatment of inflammatory bowel disease (IBD) in a dextran sulfate sodium (DSS)-induced acute colitis mouse model. PEGylated RA, synthesized

Topics: Animals; Antioxidants; Cinnamates; Colitis; Colon; Depsides; Dextran Sulfate; Disease Models, Animal; Hydrogen Peroxide; Inflammatory Bowel Diseases; Mice; Mice, Inbred C57BL; Nanoparticles; Rosmarinic Acid

The aim of this study was to investigate the effect of black rice anthocyanin-rich extract (BRAE) and rosmarinic acid (RA), alone and in combination, on dextran sulfate sodium (DSS)-induced colitis in mice. Results showed that administration of BRAE and RA, alone and in combination, significantly decreased the disease activity index (DAI) and the histological score of colons in DSS-induced colitis mice. Moreover, the administration of BRAE and RA, alone and in combination, not only reduced myeloperoxidase (MPO) and nitric oxide (NO) levels, but also inhibited the expression of pro-inflammatory mediators including interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Our results showed that BRAE decreased the histological score and TNF-α mRNA expression in a dose-dependent manner, while BRAE + RA dose-dependently attenuated the histological score and mRNA expression of IL-6. However, the benefits of RA were not dose-dependent within the dose range of 25-100 mg kg-1. The combination of BRAE and RA showed better inhibitory effect on the NO content and iNOS mRNA expression than BRAE or RA given alone, and was the most effective in ameliorating DSS-induced colitis at 100 mg kg-1. Notably, the BRAE and RA combination exhibited additive interactions in reducing MPO and NO levels, as well as the expression of some pro-inflammatory mediators (IL-6, IL-1β and iNOS), especially at 100 mg kg-1. In conclusion, dietary BRAE and RA, alone and in combination, alleviate the symptoms and inflammation of DSS-induced colitis in mice, and may provide a promising dietary approach for the management of inflammatory bowel disease.

Topics: Animals; Anthocyanins; Cinnamates; Colitis; Cyclooxygenase 2; Depsides; Dextran Sulfate; Drug Therapy, Combination; Female; Humans; Interleukin-1beta; Interleukin-6; Mice; Mice, Inbred C57BL; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Oryza; Peroxidase; Plant Extracts; Rosmarinic Acid

Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disorder of the colon. Although UC is generally treated with anti-inflammatory drugs or immunosuppressants, most of these treatments often prove to be inadequate. Rosmarinic acid (RA) is a phenolic ester included in various medicinal herbs such as Salvia miltiorrhiz and Perilla frutescens. Although RA has many biological and pharmacological activities, the anti-inflammatory effect of RA in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and underlying molecular mechanism of RA in mice with dextran sulphate sodium (DSS)-induced colitis. In the DSS-induced colitis model, RA significantly reduced the severity of colitis, as assessed by disease activity index (DAI) scores, colonic damage, and colon length. In addition, RA resulted in the reduction of the inflammatory-related cytokines, such as IL-6, IL-1β, and IL-22, and protein levels of COX-2 and iNOS in mice with DSS-induced colitis. Furthermore, RA effectively and pleiotropically inhibited nuclear factor-kappa B and signal transducer and activator of transcription 3 activation, and subsequently reduced the activity of pro-survival genes that depend on these transcription factors. These results demonstrate that RA has an ameliorative effect on colonic inflammation and thus a potential therapeutic role in colitis.

Topics: Animals; Cinnamates; Colitis; Colon; Cyclooxygenase 2; Cytokines; Depsides; Dextran Sulfate; Disease Models, Animal; Disease Progression; Gene Expression Regulation; Inflammation; Inflammation Mediators; Male; Mice, Inbred ICR; NF-kappa B; Nitric Oxide Synthase Type II; Peroxidase; Rosmarinic Acid; Spleen; STAT3 Transcription Factor

Inhibition of hypoxia inducible factor-prolyl hydroxylase-2 (HPH), leading to activation of hypoxia inducible factor (HIF)-1 is a potential therapeutic strategy for the treatment of colitis. Rosmarinic acid (RA), an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid is a naturally occurring polyphenolic compound with two catechols, a or inhibition of HPH. To improve accessibility of highly hydrophilic RA to HPH, an intracellular target, RA was chemically modified to decrease hydrophilicity. Of the less-hydrophilic derivatives, rosmarinic acid methyl ester (RAME) most potently inhibited HPH. Accordingly, RAME prevented hydroxylation of HIF-1α and consequently stabilized HIF-1α protein in cells. RAME inhibition of HPH and induction of HIF-1α were diminished by elevated doses of the required factors of HPH, 2-ketoglutarate and ascorbate. RAME induction of HIF-1α led to activation of an ulcer healing pathway, HIF-1-vascular endothelial growth factor (VEGF), in human colon carcinoma cells. RAME administered rectally ameliorated TNBS-induced rat colitis and substantially decreased the levels of pro-inflammatory mediators in the inflamed colonic tissue. In parallel with the cellular effects of RAME, RAME up-regulated HIF-1α and VEGF in the inflamed colonic tissue. Thus, lipophilic modification of RA improves its ability to inhibit HPH, leading to activation of the HIF-1-VEGF pathway. RAME, a lipophilic RA derivative, may exert anti-colitic effects via activation of the ulcer healing pathway.

Topics: Animals; Ascorbic Acid; Carboxylic Acids; Cell Line, Tumor; Cinnamates; Coenzymes; Colitis; Depsides; Enzyme Inhibitors; Esters; Humans; Hydrophobic and Hydrophilic Interactions; Hydroxylation; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Ketoglutaric Acids; Protein Stability; Rats; Rosmarinic Acid; Signal Transduction; Structure-Activity Relationship; Trinitrobenzenesulfonic Acid; Vascular Endothelial Growth Factor A