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Amination Potentially Augments the Ameliorative Effect of Curcumin on Inhibition of the IL-6/Stat3/c-Myc Pathway and Gut Microbial Modulation in Colitis-Associated Tumorigenesis
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-11-11 , DOI: 10.1021/acs.jafc.2c06645 Yen-Chun Koh, Yi-Wen Tsai, Pei-Sheng Lee, Kalyanam Nagabhushanam, Chi-Tang Ho, Min-Hsiung Pan
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-11-11 , DOI: 10.1021/acs.jafc.2c06645 Yen-Chun Koh, Yi-Wen Tsai, Pei-Sheng Lee, Kalyanam Nagabhushanam, Chi-Tang Ho, Min-Hsiung Pan
Epigallocatechin gallate and tetrahydrocurcumin are aminated as colonic metabolites, preserving their bioactivities and improving their capabilities. We compared the bioactivities of unaminated (CUR) and aminated (AC) curcumin in inflammatory colitis-associated tumorigenesis. The anti-inflammatory and anticancer capabilities of CUR and AC were evaluated using RAW264.7 and HT29 cell lines, respectively. An azoxymethane/dextran sodium sulfate-induced colitis-associated carcinogenesis mouse model was used with CUR and two-dose AC interventions. AC had a greater anti-inflammatory effect but a similar anticancer effect as CUR in vitro. CUR and low-dose AC (LAC) significantly preserved colon length and reduced tumor number in vivo. Both CUR and LAC inhibited activation of the protein kinase B (AKT)/nuclear factor kappa B (NF-κB) signaling pathway, its downstream cytokines, and the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3)/c-myelocytomatosis oncogene (c-MYC) pathway. However, only LAC significantly preserved E-cadherin, reduced N-cadherin, and facilitated beneficial gut microbial growth, including Akkermansia and Bacteroides, potentially explaining AC’s better ameliorative effect at low than high doses.
中文翻译:
胺化作用可能会增强姜黄素对 IL-6/Stat3/c-Myc 通路抑制和结肠炎相关肿瘤发生中肠道微生物调节的改善作用
表没食子儿茶素没食子酸酯和四氢姜黄素被胺化为结肠代谢物,保留了它们的生物活性并提高了它们的能力。我们比较了未胺化 (CUR) 和胺化 (AC) 姜黄素在炎症性结肠炎相关肿瘤发生中的生物活性。分别使用 RAW264.7 和 HT29 细胞系评估了 CUR 和 AC 的抗炎和抗癌能力。氧化偶氮甲烷/葡聚糖硫酸钠诱导的结肠炎相关致癌小鼠模型与 CUR 和两剂量 AC 干预一起使用。AC 具有更强的抗炎作用,但在体外与 CUR 具有相似的抗癌作用。CUR 和低剂量 AC (LAC) 显着保留了结肠长度并减少了体内肿瘤数量。CUR 和 LAC 均抑制蛋白激酶 B (AKT)/核因子 kappa B (NF-κB) 信号通路的激活,其下游细胞因子,以及白介素 (IL)-6/信号转导和转录激活因子 3 (STAT3)/c-myelocytomatosis 癌基因 (c-MYC) 通路。然而,只有 LAC 显着保留了 E-钙粘蛋白,减少了 N-钙粘蛋白,并促进了有益的肠道微生物生长,包括Akkermansia和Bacteroides,可能解释了 AC 在低剂量下比在高剂量下具有更好的改善效果。
更新日期:2022-11-11
中文翻译:
胺化作用可能会增强姜黄素对 IL-6/Stat3/c-Myc 通路抑制和结肠炎相关肿瘤发生中肠道微生物调节的改善作用
表没食子儿茶素没食子酸酯和四氢姜黄素被胺化为结肠代谢物,保留了它们的生物活性并提高了它们的能力。我们比较了未胺化 (CUR) 和胺化 (AC) 姜黄素在炎症性结肠炎相关肿瘤发生中的生物活性。分别使用 RAW264.7 和 HT29 细胞系评估了 CUR 和 AC 的抗炎和抗癌能力。氧化偶氮甲烷/葡聚糖硫酸钠诱导的结肠炎相关致癌小鼠模型与 CUR 和两剂量 AC 干预一起使用。AC 具有更强的抗炎作用,但在体外与 CUR 具有相似的抗癌作用。CUR 和低剂量 AC (LAC) 显着保留了结肠长度并减少了体内肿瘤数量。CUR 和 LAC 均抑制蛋白激酶 B (AKT)/核因子 kappa B (NF-κB) 信号通路的激活,其下游细胞因子,以及白介素 (IL)-6/信号转导和转录激活因子 3 (STAT3)/c-myelocytomatosis 癌基因 (c-MYC) 通路。然而,只有 LAC 显着保留了 E-钙粘蛋白,减少了 N-钙粘蛋白,并促进了有益的肠道微生物生长,包括Akkermansia和Bacteroides,可能解释了 AC 在低剂量下比在高剂量下具有更好的改善效果。