Deferiprone-Gallium-Protoporphyrin Chitogel Decreases Pseudomonas aeruginosa Biofilm Infection without Impairing Wound Healing.

Pseudomonas aeruginosa is one of the most common pathogens encountered in clinical wound infections. Clinical studies have shown that P. aeruginosa infection results in a larger wound area, inhibiting healing, and a high prevalence of antimicrobial resistance. Hydroxypyridinone-derived iron chelator Deferiprone (Def) and heme analogue Gallium-Protoporphyrin (GaPP) in a chitosan-dextran hydrogel (Chitogel) have previously been demonstrated to be effective against PAO1 and clinical isolates of P. aeruginosa in vitro. Moreover, this combination of these two agents has been shown to improve sinus surgery outcomes by quickly reducing bleeding and preventing adhesions. In this study, the efficacy of Def-GaPP Chitogel was investigated in a P. aeruginosa biofilm-infected wound murine model over 6 days. Two concentrations of Def-GaPP Chitogel were investigated: Def-GaPP high dose (10 mM Def + 500 µg/mL GaPP) and Def-GaPP low dose (5 mM Def + 200 µg/mL GaPP). The high-dose Def-GaPP treatment reduced bacterial burden in vivo from day 2, without delaying wound closure. Additionally, Def-GaPP treatment decreased wound inflammation, as demonstrated by reduced neutrophil infiltration and increased anti-inflammatory M2 macrophage presence within the wound bed to drive wound healing progression. Def-GaPP Chitogel treatment shows promising potential in reducing P. aeruginosa cutaneous infection with positive effects observed in the progression of wound healing.

Emu Oil and Saireito in combination reduce tumour development and clinical indicators of disease in a mouse model of colitis-associated colorectal cancer.

BACKGROUND: Emu Oil (EO) previously demonstrated therapeutic potential in a mouse model of colitis-associated CRC (CA-CRC). Saireito, a traditional Japanese medicine, has not been investigated in CA-CRC. AIM: To determine whether EO and Saireito could be therapeutic in an azoxymethane (AOM)/dextran sulphate sodium (DSS) model of CA-CRC. METHODS: Female C57BL/6 mice were assigned to groups (n = 10/group); 1) saline control, 2) saline+Saireito, 3) saline+EO, 4) saline+EO/Saireito, 5) AOM/DSS control, 6) AOM/DSS+Saireito, 7) AOM/DSS+EO and 8) AOM/DSS+EO/Saireito. Mice were intraperitoneally injected with saline or AOM (7.4 mg/kg) on day 0 and underwent three DSS/water cycles (2%w/v DSS for 7 days, 14 days water). Mice were orally-gavaged with either water (80 µL), Saireito (80 µL), EO (80 µL) or EO/Saireito (160 µL; 80 µL EO + 80 µL Saireito) thrice weekly. Daily bodyweight and disease activity index (DAI) were recorded and colonoscopies performed on days 20, 41 and 62. Mice were euthanized on day 63. p < 0.05 was considered statistically significant. RESULTS: AOM/DSS induced significant bodyweight loss throughout the trial (max -36%), which was attenuated by Saireito (max +7%), EO (max +5%) and EO/Saireito (max +14%; p < 0.05). AOM/DSS increased DAI compared to saline controls (p < 0.05), which was reduced by Saireito, EO and EO/Saireito (p < 0.05). All treatments reduced colonoscopically-assessed colitis severity (days 20 and 41; p < 0.05). EO/Saireito further decreased colitis severity compared to Saireito and EO alone (day 20; p < 0.05). Finally, EO and EO/Saireito resulted in fewer colonic tumours compared to AOM/DSS controls (p < 0.05). CONCLUSION: Combined EO and Saireito reduced disease and tumour development in AOM/DSS mice, suggesting therapeutic potential in CA-CRC.

Emu oil and grape seed extract reduce tumour burden and disease parameters in murine colitis-associated colorectal cancer.

Ulcerative colitis is an incurable condition whereby patients are at an increased risk of developing colorectal cancer (CRC). We aimed to investigate the combination of Emu oil (EO) and grape seed extract (GSE) in an azoxymethane (AOM)/dextran sulphate sodium (DSS) model of colitis-associated CRC (CA-CRC). C57BL/6 mice (n = 10/group) were injected i.p. with saline or AOM (7.4 mg/kg) and underwent three DSS/water cycles. Mice were orally-gavaged thrice weekly with water (80 µl), EO (80 µl), GSE (80 µl; 400 mg/kg) or combined EO/GSE (160 µl). Mice were euthanized on day 63. AOM/DSS induced significant bodyweight loss (max -21%) and increased disease activity index (DAI) (max +83%) throughout the trial (P < 0.05). EO (max -53%), GSE (max -51%) and EO/GSE (max -71%) reduced DAI scores in AOM/DSS mice in all DSS cycles (P < 0.05). EO/GSE-treatment in AOM/DSS mice resulted in further DAI reduction compared with EO (max -62%) and GSE (max -71%) alone (P < 0.05). AOM/DSS mice presented with severe colonoscopically-assessed colitis at all time-points, which was reduced by EO, GSE and EO/GSE (P < 0.05). EO, GSE and EO/GSE reduced the number of colonic tumours compared with AOM/DSS controls (P < 0.05). Myeloperoxidase (acute inflammation) and fluorescein isothiocyanate-dextran levels (intestinal permeability) were increased in AOM/DSS controls (P < 0.05). EO (-58%) and EO/GSE (-77%) reduced fluorescein isothiocyanate-dextran compared with AOM/DSS controls (P < 0.05), with no effect on myeloperoxidase. Histologically-assessed severity scores were increased in the distal colon of AOM/DSS mice compared with saline (P < 0.05), with no effect observed following treatment. The combination of EO and GSE improved clinical indicators and reduced colonic tumours in AOM/DSS treated mice, suggesting potential in CA-CRC management.

Combined Nutraceuticals: A Novel Approach to Colitis-Associated Colorectal Cancer?

Ulcerative colitis is an unremitting and lifelong inflammatory bowel disease that is increasing in prevalence worldwide. Patients display various clinical symptoms such as abdominal pain, diarrhea and fatigue. The etiology of ulcerative colitis remains unknown and the current pharmaceutical treatments are variably effective and not curative, highlighting the need for improved therapeutic approaches. Furthermore, patients with ulcerative colitis are at an increased risk of developing colorectal cancer. Some naturally sourced agents, named nutraceuticals, have been identified to possess anti-inflammatory and antioxidant properties. Of particular interest is Emu Oil, grape seed extract and Japanese Kampo medicine. Previously, Emu Oil has protected and repaired intestinal damage in models of gastrointestinal diseases including colitis and colitis-associated colorectal cancer. Additionally, grape seed extract possesses anticancer properties in vitro. Moreover, Kampo medicine, composed of herbal ingredients, is widely used in Japan for the treatment of various medical conditions and has demonstrated efficacy in targeting cancer cells in vitro. Nutraceuticals in combination have not yet been widely investigated in a setting of colitis-associated colorectal cancer. Investigation into the efficacy of Emu Oil combined with other nutraceuticals, including grape seed extract and Kampo medicine, is warranted as they may provide a novel approach to conventional colitis and colorectal cancer management.

Emu Oil Combined with Lyprinol™ Reduces Small Intestinal Damage in a Rat Model of Chemotherapy-Induced Mucositis.

Chemotherapy-induced mucositis is characterized by inflammation and ulcerating lesions lining the alimentary tract. Emu Oil and Lyprinol™ have independently demonstrated their therapeutic potential in intestinal inflammatory disorders, including mucositis. We investigated Emu Oil and Lyprinol™ in combination for their further potential to alleviate chemotherapy-induced mucositis in rats. Rats were gavaged with (1 ml) water, Olive Oil, Emu Oil + Olive Oil, Lyprinol™ + Olive Oil or Emu Oil + Lyprinol™ from Days 0 to 7, injected with saline (control) or 5-Fluorouracil (5-FU) on Day 5 and euthanized on Day 8. Myeloperoxidase (MPO) activity (indicative of acute inflammation), histological severity scores, and intestinal architecture were quantified. Myeloperoxidase activity was significantly increased in the jejunum and ileum following 5-FU, compared to saline controls. Both Olive Oil and Emu Oil + Lyprinol™ significantly reduced jejunal MPO levels (1.8-fold and 1.7-fold, respectively), whereas only Emu Oil + Lyprinol™ significantly decreased ileal MPO levels, relative to 5-FU controls. All oil treatments decreased histological severity scores in the jejunum and ileum, and normalized crypt depth in the mid small intestine, relative to 5-FU controls. Emu Oil combined with Lyprinol™ partially reduced acute small intestinal inflammation. Isolating bioactive constituents of these naturally sourced oils could provide a more targeted strategy to protect against intestinal mucositis.

Clinical and structural effects of traditional Chinese medicine and the herbal preparation, Iberogast, in a rat model of ulcerative colitis.

Plant-sourced formulations such as Iberogast and the traditional Chinese medicine formulation, Cmed, purportedly possess anti-inflammatory and radical scavenging properties. We investigated Iberogast and Cmed, independently, for their potential to decrease the severity of the large bowel inflammatory disorder, ulcerative colitis. Sprague Dawley rats (n = 8/group) received daily 1 mL gavages (days 0-13) of water, Iberogast (100 µL/200 µL), or Cmed (10 mg/20 mg). Rats ingested 2% dextran sulfate sodium or water ad libitum for 7 days commencing on day 5. Dextran sulfate sodium administration increased disease activity index scores from days 6 to 12, compared with water controls (P < .05). On day 10, 200 µL Iberogast decreased disease activity index scores in colitic rats compared with colitic controls (P < .05). Neither Iberogast nor Cmed achieved statistical significance for daily metabolic parameters or colonic crypt depth. The therapeutic effects of Iberogast and Cmed were minimal in the colitis setting. Further studies of plant extracts are required investigating greater concentrations and alternative delivery systems.

The herbal extract, Iberogast, improves jejunal integrity in rats with 5-Fluorouracil (5-FU)-induced mucositis.

There is an acute need for the development of effective therapies for mucositis, a debilitating side effect of cancer chemotherapy. Iberogast is a herbal extract reported to possess anti-inflammatory properties. We investigated Iberogast for its potential to reduce the severity of 5-Fluorouracil (FU)-induced mucositis in rats. Rats were allocated to three treatment groups (n = 8) and gavaged daily with a 10% solution of Iberogast or water from day 0 to day 8. Rats were injected intraperitoneally with 5-FU (150 mg/kg) or saline on day 6, and killed after 72 h. In vivo and in vitro sucrase activity was assessed by (13)C-sucrose breath test (SBT) and sucrase assay respectively. Intestinal disease severity was determined by histological assessment of villus height and crypt depth. Significant increases in villus height (277 +/- 9 microm) and crypt depth (67 +/- 3 microm) were observed in 5-FU + Iberogast-treated rats compared with 5-FU + Water (224 +/- 13 microm and 48 +/- 2 microm respectively; p < 0.05). Sucrase activity was significantly reduced in all 5-FU groups compared to control. Significant reductions in SBT and sucrase activity were observed in all 5-FU groups compared with Saline + Water controls (p < 0.05). We conclude that although Iberogast partially improved the histopathological features of 5-FU induced mucositis, it conferred no significant protection as indicated by the assessed endpoints.