Emu Oil And Grape Seed Extract Reduce Tumour Burden And Disease Parameters In Murine Colitis-Associated Colorectal Cancer

Ulcerative colitis (UC) 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 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 (7.4mg/kg) and underwent three DSS/water cycles. Mice were orally-gavaged thrice weekly with water (80μL), EO (80μL), GSE (80μL; 400mg/kg) or combined EO/GSE (160μL). Mice were euthanized on day 63. AOM/DSS induced significant bodyweight loss (max -21%) and increased 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 to 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 to AOM/DSS controls (p<0.05). Myeloperoxidase (acute inflammation) and FITC-dextran levels (intestinal permeability) were increased in AOM/DSS controls (p<0.05). EO (-58%) and EO/GSE (-77%) reduced FITC-dextran compared to AOM/DSS controls (p<0.05), with no effect on MPO. Histologically-assessed severity scores were increased in the distal colon of AOM/DSS mice compared to 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

Orally administered emu oil attenuates disease in a mouse model of Crohn’s-like colitis

Crohn’s disease is a severe, incurable inflammatory bowel disease. Orally administered emu oil has demonstrated anti-inflammatory properties in previous models of gastrointestinal disease. We aimed to determine whether orally administered emu oil could attenuate disease in a mouse model of Crohn’s-like colitis. Female ARC(s) mice (CD-1 equivalent, n = 10/group) were intra-rectally administered water (120 μL) or trinitrobenzene sulfonic acid (TNBS; 3 mg in 50% ethanol; 120 μL bolus) on day 0. Mice were orally administered water (80 μL) or emu oil (80 μL or 160 μL) daily for five days and euthanized on day six. Bodyweight and disease activity were recorded daily. Colonoscopy, burrowing activity, facial grimace, histological parameters (damage severity, small intestinal villus height/crypt depth and colonic crypt depth), myeloperoxidase activity and intestinal permeability were assessed. P < 0.05 was considered statistically significant. TNBS decreased bodyweight (days 1, 2, 4; P < 0.05) and increased disease activity (days 1–6; P < 0.01), compared to normal controls. Emu oil (80 μL) attenuated disease activity on days 5–6 ( P < 0.05), although bodyweight loss was not significantly impacted ( P > 0.05). Facial grimace and colonoscopy scores were significantly increased in TNBS-control mice; effects attenuated by both volumes of emu oil ( P < 0.001). TNBS increased histological damage severity compared to normal controls ( P < 0.05); an effect attenuated by 80 μL emu oil (proximal and distal colon; P < 0.05) and 160 μL emu oil (distal colon; P < 0.01). In the ileum, villus height and crypt depth were unaffected by TNBS or emu oil treatment compared to normal ( P > 0.05). TNBS-induced distal colonic crypt lengthening was unaffected following emu oil administration ( P > 0.05). Remaining parameters, including burrowing, myeloperoxidase activity and intestinal permeability, were unchanged across all treatment groups ( P > 0.05). In normal mice, emu oil treatment did not significantly impact any parameter compared to normal controls. In conclusion, emu oil reduced overall disease severity and facial grimace scores in TNBS mice. These results suggest therapeutic potential for orally administered emu oil in the management of Crohn’s disease.

Efficacy of Emu Oil Transfersomes for Local Transdermal Delivery of 4-OH Tamoxifen in the Treatment of Breast Cancer

Oral tamoxifen used in the prevention and treatment of ductal carcinoma in situ (DCIS) (estrogen-positive) patients has limited acceptance, due to its adverse side effects. The efficacy of tamoxifen is related to its major metabolite, 4-hydroxytamoxifen. Local transdermal therapy of 4-hydroxytamoxifen to the breast might avert the toxicity of oral tamoxifen, while maintaining efficacy. We aim to study the skin irritancy, as well as to evaluate the efficacy of the developed transfersome formulations, with/without emu oil, using a syngeneic mouse model of breast cancer. We also quantified tamoxifen/4-hydroxytamoxifen concentrations in blood plasma and performed histopathology. The skin irritancy test showed that the pure emu oil and transfersome formulations with or without the emu oil did not cause skin irritancy in the animals studied. A sensitive and specific LC–MS/MS method for the quantification of tamoxifen and 4-hydroxytamoxifen was developed and validated. Studies on tumor volume and necrosis (histopathology) using the breast cancer mouse model showed that the 4-OHT transfersomal formulations, with and without emu oil, showed comparable efficacy with that of orally administered tamoxifen. However, the transfersomal formulations, with and without emu oil, resulted in significantly lower (10.24 ± 0.07 and 32.45 ± 0.48 ng/mL, respectively) plasma concentrations of 4-hydroxytamoxifen, compared to the oral tamoxifen (TAMX) group (634.42 ± 7.54 ng/mL). This study demonstrated the potential use of emu oil in a local transdermal formulation for the treatment of breast cancer and its reduced adverse effects.