Discipline of Physiology, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Gastroenterology Department, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
Department of Paediatric Surgery, Saitama Medical Centre, Dokkyo Medical University, Saitama, Japan.
Biomed Pharmacother. 2021 Jun;138:111478. doi: 10.1016/j.biopha.2021.111478. Epub 2021 Mar 20.
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.
To determine whether EO and Saireito could be therapeutic in an azoxymethane (AOM)/dextran sulphate sodium (DSS) model of CA-CRC.
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.
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).
Combined EO and Saireito reduced disease and tumour development in AOM/DSS mice, suggesting therapeutic potential in CA-CRC.
鸸鹋油(EO)先前在结肠炎相关结直肠癌(CA-CRC)的小鼠模型中显示出治疗潜力。传统的日本药物薬味方剂(Saireito)尚未在 CA-CRC 中进行研究。
确定 EO 和薬味方剂是否可在氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导的 CA-CRC 模型中具有治疗作用。
将雌性 C57BL/6 小鼠分为以下几组(每组 n=10):1)生理盐水对照,2)生理盐水+薬味方剂,3)生理盐水+EO,4)生理盐水+EO/薬味方剂,5)AOM/DSS 对照,6)AOM/DSS+薬味方剂,7)AOM/DSS+EO 和 8)AOM/DSS+EO/薬味方剂。在第 0 天,小鼠经腹腔注射生理盐水或 AOM(7.4mg/kg),并进行三次 DSS/水循环(7 天,2%w/v DSS,14 天水)。每周三次通过口服给予小鼠水(80µL)、薬味方剂(80µL)、EO(80µL)或 EO/薬味方剂(160µL;80µL EO+80µL 薬味方剂)。在第 20、41 和 62 天进行结肠镜检查,并记录每日体重和疾病活动指数(DAI)。在第 63 天处死小鼠。p<0.05 被认为具有统计学意义。
AOM/DSS 在整个试验过程中引起显著的体重减轻(最大-36%),而薬味方剂(最大+7%)、EO(最大+5%)和 EO/薬味方剂(最大+14%;p<0.05)则减轻了体重减轻。与生理盐水对照组相比,AOM/DSS 增加了 DAI(p<0.05),而薬味方剂、EO 和 EO/薬味方剂则降低了 DAI(p<0.05)。所有治疗方法均减轻了结肠镜评估的结肠炎严重程度(第 20 和 41 天;p<0.05)。与单独的薬味方剂和 EO 相比,EO/薬味方剂进一步减轻了结肠炎的严重程度(第 20 天;p<0.05)。最后,与 AOM/DSS 对照组相比,EO 和 EO/薬味方剂导致更少的结肠肿瘤(p<0.05)。
EO 和薬味方剂联合使用可减少 AOM/DSS 小鼠的疾病和肿瘤发生,提示其在 CA-CRC 中的治疗潜力。