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富含α-亚麻酸的紫苏籽油冷榨提取物可减轻结肠炎相关结直肠癌AOM/DSS小鼠模型中的肿瘤进展并恢复肠道微生物稳态。

Cold-pressed extraction of perilla seed oil enriched with alpha-linolenic acid mitigates tumour progression and restores gut microbial homeostasis in the AOM/DSS mice model of colitis-associated colorectal cancer.

作者信息

Korsirikoon Chawin, Techaniyom Peerapa, Kettawan Aikkarach, Rungruang Thanaporn, Metheetrairut Chanatip, Prombutara Pinidphon, Kettawan Aurawan Kringkasemsee

机构信息

Doctor of Philosophy Program in Nutrition, Faculty of Medicine Ramathibodi Hospital and Institute of Nutrition, Mahidol University, Bangkok, Thailand.

Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand.

出版信息

PLoS One. 2024 Dec 9;19(12):e0315172. doi: 10.1371/journal.pone.0315172. eCollection 2024.

DOI:10.1371/journal.pone.0315172
PMID:39652552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11627366/
Abstract

The present investigation explores into the influence of dietary nutrients, particularly alpha-linolenic acid (ALA), a plant-derived omega-3 fatty acid abundant in perilla seed oil (PSO), on the development of colitis-associated colorectal cancer (CRC). The study employs a mouse model to scrutinize the effects of ALA-rich PSO in the context of inflammation-driven CRC. Perilla seeds were subjected to oil extraction, and the nutritional composition of the obtained oil was analysed. Male ICR mice, initiated at four weeks of age, were subjected to diets comprising 5%, 10%, or 20% PSO, 10% fish oil, or 5% soybean oil. All groups, with the exception of the control group (5% soybean oil), underwent induction with azoxymethane (AOM) and dextran sulphate sodium (DSS) to instigate CRC. Disease development, colon samples, preneoplastic lesions, dysplasia, and biomarkers were meticulously evaluated. Furthermore, gut microbiota composition was elucidated through 16S rRNA sequencing. The analysis revealed that PSO contained 61.32% ALA and 783.90 mg/kg tocopherols. Mice subjected to diets comprising 5% soybean or 10% fish oil exhibited higher tumour incidence, burden, multiplicity, and aberrant crypt counts. Remarkably, these parameters were significantly reduced in mice fed a 5% PSO diet. Additionally, 5% PSO-fed mice displayed reduced proliferative and pro-inflammatory markers in colon tissues, coupled with an alleviation of AOM/DSS-induced gut dysbiosis. Notably, PSO demonstrated inhibitory effects on colitis-associated CRC in the AOM/DSS mice model, achieved through the suppression of proliferative and pro-inflammatory protein levels, and mitigation of gut dysbiosis, with discernible efficacy observed at a 5% dietary concentration.

摘要

本研究探讨膳食营养素,特别是α-亚麻酸(ALA),一种紫苏籽油(PSO)中富含的植物源ω-3脂肪酸,对结肠炎相关结直肠癌(CRC)发生发展的影响。该研究采用小鼠模型,在炎症驱动的CRC背景下仔细研究富含ALA的PSO的作用。对紫苏籽进行榨油,并分析所得油的营养成分。4周龄开始的雄性ICR小鼠分别给予含5%、10%或20%PSO、10%鱼油或5%大豆油的饮食。除对照组(5%大豆油)外,所有组均用氧化偶氮甲烷(AOM)和葡聚糖硫酸钠(DSS)诱导以引发CRC。对疾病发展、结肠样本、癌前病变、发育异常和生物标志物进行了细致评估。此外,通过16S rRNA测序阐明肠道微生物群组成。分析显示,PSO含有61.32%的ALA和783.90mg/kg生育酚。给予含5%大豆油或10%鱼油饮食的小鼠表现出更高的肿瘤发生率、负担、多发性和异常隐窝计数。值得注意的是,在给予5%PSO饮食的小鼠中,这些参数显著降低。此外,给予5%PSO饮食的小鼠结肠组织中增殖和促炎标志物减少,同时AOM/DSS诱导的肠道生态失调得到缓解。值得注意的是,PSO在AOM/DSS小鼠模型中对结肠炎相关CRC具有抑制作用,这是通过抑制增殖和促炎蛋白水平以及减轻肠道生态失调实现的,在5%的饮食浓度下可观察到明显的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/11627366/b056cb012351/pone.0315172.g008.jpg
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