iridoids and Colitis--Ulcerative

Morroniside and loganin are iridoid glycosides extracted from Cornus officinalis, a plant species widely used in traditional Chinese medicine. However, the anti-inflammatory effects of morroniside and loganin in colitis are barely understood. The aim of the present study was to explore the effects of morroniside and loganin on the dextran sodium sulfate (DSS)-induced murine model of colitis and an LPS-induced colorectal cancer (CRC) cell inflammation model, and to clarify the underlying mechanisms. We found that morroniside and loganin were able to ameliorate clinical features, including disease activity index (DAI), histological inflammation score and periodic acid-Schiff staining (PAS). In the mouse model, morroniside and loganin treatment increased expression of tight junction proteins (TJs) and decreased pro-inflammatory cytokine production. Moreover, our findings showed that the expression of p-STAT3 and p-p65 were suppressed compared to the disease group. In in vitro experiments, treatment with morroniside and loganin had no obvious effects on proliferative activity in HCT116 cells and HIEC-6 cells. Expression of pro-inflammatory cytokines was inhibited by morroniside and loganin treatment in comparison with the LPS-treated group. Taken together, morroniside and loganin have beneficial effects on colitis in vivo and are anti-inflammatory in vitro. Possible mechanisms of the anti-inflammatory response may include blockade of the STAT3/NF-κB pathway.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Colitis; Colitis, Ulcerative; Cornus; Dextran Sulfate; Disease Models, Animal; Glycosides; Humans; Iridoid Glycosides; Iridoids; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; NF-kappa B; Phosphorylation; Signal Transduction; STAT3 Transcription Factor

Curcumin (CUR) is a promising edible phytochemical compound with ideal ulcerative colitis (UC) treatment activity; however, it is characteristically instable in the digestive tract and has a short retention time in colon. Therefore, we designed and fabricated an oral food-grade nanocarrier composed of tannic acid (TA)-coated, Genipin (Gnp)-crosslinked human serum albumin (HSA) to encapsulate CUR (TA/CUR-NPs). The resulting CUR nanoparticles (NPs) were about 220 nm and -28.8 mV. With the assistance of TA layer and Gnp-crosslinking, the entire nano-scaled system effectively delayed CUR release in simulated gastric fluid, prolonged its colon adhesion and increased its uptake in Caco-2 cells. As expected, TA/CUR-NPs oral administration significantly alleviated colitis symptoms in DSS-treated mice when compared with controls by inhibiting the TLR4-linked NF-κB signaling pathway. Collectively, this study indicates that we have developed a convenient, eco-friendly, nano-scaled vehicle for oral delivery of CUR with anti-UC benefit.

Topics: Administration, Oral; Animals; Caco-2 Cells; Colitis, Ulcerative; Curcumin; Drug Delivery Systems; Humans; Iridoids; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Serum Albumin, Human; Tannins

Loganin, a major bioactive iridoid glycoside derived from Cornus officinalis, exerts different beneficial biological properties. Recently, loganin has been reported to exhibit potential anti-inflammatory effects in the intestinal tissues, while the detailed mechanisms remain elusive. This study aimed to investigate whether loganin could inhibit the inflammatory response in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and to explore possible molecular mechanisms involved in this process. Results showed that oral administration of loganin significantly decreased body weight loss, disease activity index, colon shortening, myeloperoxidase (MPO) activity and pathologic abnormalities in UC mice. Loganin obviously inhibited the mRNA and protein levels of IL-6, TNF-α and IL-1β in colon tissues from UC mice. Furthermore, loganin remarkably reduced macrophage M1 polarization in UC mice evidenced by reduced the number of F4/80 and iNOS dual-stained M1 macrophages, and the expression of M1 macrophage-related pro-inflammatory chemokines/cytokines including MCP-1, CXCL10 as well as COX-2. Further investigation showed that loganin upregulated the mRNA and protein levels of Sirt1, with the inhibition of NF-κB-p65 acetylation in colon tissues from UC mice. Moreover, Sirt1-specific inhibitor Ex527 administration abolished the anti-inflammatory and anti-macrophage M1 polarization effects of loganin in UC. Thus, loganin could inhibit M1 macrophage-mediated inflammation and modulate Sirt1/NF-κB signaling pathway to attenuate DSS-induced UC. Loganin was considered as a viable natural strategy in the treatment of UC.[Figure: see text].

Topics: Animals; Blotting, Western; Colitis, Ulcerative; Cytokines; Iridoids; Macrophages; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Real-Time Polymerase Chain Reaction; Signal Transduction; Sirtuin 1

Ulcerative colitis (UC), an idiopathic inflammatory bowel disease, not only affects millions of patients worldwide, but also increases the risk of colon cancer. Geniposide is an iridoid glycoside and has many biological activities such as anti-inflammatory and antioxidant. However, its protective efficacy and mechanism of action against UC are still unclear. In this study, we aimed to investigate the protective effects and mechanisms of geniposide on dextran sulfate sodium (DSS)-induced experimental colitis in mice. The results revealed that geniposide alleviated body weight loss, disease activity index, colon length shortening and colonic pathological damage induced by DSS. Geniposide significantly suppressed pro-inflammatory cytokines by regulating NF-κB and PPARγ pathways in vivo and in vitro. Furthermore, geniposide also significantly regulated the expressions of ZO-1 and occludin in DSS-induced experimental colitis in mice and lipopolysaccharide (LPS)-triggered inflammation in Caco-2 cells. These findings indicated that geniposide may be a new natural chemopreventive agent to combat UC.

Topics: Animals; Anti-Inflammatory Agents; Caco-2 Cells; Colitis; Colitis, Ulcerative; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Humans; Inflammation; Inflammation Mediators; Intestinal Mucosa; Iridoids; Male; Mice; Mice, Inbred C57BL; NF-kappa B; PPAR gamma; Signal Transduction

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Caco-2 Cells; Colitis, Ulcerative; Cytokines; Down-Regulation; Humans; Intestinal Mucosa; Iridoids; Male; Neutrophil Infiltration; Permeability; Rats, Sprague-Dawley; Sulfasalazine; Trinitrobenzenesulfonic Acid; Up-Regulation