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万寿菊花精油通过 Nrf2/HO-1/NF-κB/p65 轴对 N-甲基-N'-硝基-N-亚硝基胍(MNNG)诱导的大鼠胃癌的调节作用。

Modulatory effect of Tagetes erecta flowers essential oils via Nrf2/HO-1/NF-κB/p65 axis mediated suppression of N-methyl-N'nitro-N-nitroguanidine (MNNG) induced gastric cancer in rats.

机构信息

Department of Traditional Chinese Medicine, The First Affiliated Hospital With Nanjing Medical University, Nanjing City, 210029, China.

Institute of Integration of Chinese and Western Medicine, Nanjing Medical University, Nanjing City, 210029, China.

出版信息

Mol Cell Biochem. 2021 Mar;476(3):1541-1554. doi: 10.1007/s11010-020-04005-0. Epub 2021 Jan 4.

DOI:10.1007/s11010-020-04005-0
PMID:33394271
Abstract

Protective effect of Tagetes erecta flowers essential oils was investigated on oxidative stress, immune response, inflammation, and apoptosis against N-methyl-N'nitro-N-nitroguanidine (MNNG) induced gastric cancer in rats. Essential oil were extracted from Tagetes erecta flowers and analyzed using gas chromatography-mass spectrometry (GC-MS). For observing a protective effect against MNNG induced gastric cancer, we divided rats into 4 groups (group A to D) having 10 rats in each group. Performed various experiments and measured a different parameters to investigate antioxidant activity, immune response, anti-inflammatory and anti-apoptotic activity. The levels of malondialdehyde were markedly increased in the presence of N-methyl-N'nitro-N-nitroguanidine, whereas, the antioxidant activities of superoxide dismutase, and catalase were lowered in the treated rats in contrast with the control. Intervention with TEEO to gastric cancer-induced rats upregulated the redox status and the activity of the immune system to decrease cancer risk. The proinflammatory cytokines (IL-6 and TNF-α) secretions that were induced by MNNG were markedly inhibited by TEEO. Administration of TEEO also significantly reduced terminal deoxynucleotidyl transferase dUTP nick end labeling positive gastric cancer cells, expression of mRNA of caspase-3, and Bax. Whereas, the expression of Bcl-2 was increased. Additionally, downregulation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) and IκBα degradation and the nuclear factor-κB (NF-κB) p65 expression in tissues of the stomach of MNNG-induced-rats were markedly elevated due to TEEO. This suggested possession of TEEO with a protective shield against MNNG induced gastric cancer by the exertion of antioxidative stress, anti-apoptotic response, the anti-inflammatory response through Nrf2/HO-1, and NF-κB signaling pathways.

摘要

从万寿菊花中提取的精油对 N-甲基-N'-硝基-N-亚硝基胍(MNNG)诱导的大鼠胃癌的氧化应激、免疫反应、炎症和细胞凋亡的保护作用。使用气相色谱-质谱联用仪(GC-MS)对精油进行分析。为了观察对 MNNG 诱导的胃癌的保护作用,我们将大鼠分为 4 组(A 组至 D 组),每组 10 只。进行了各种实验并测量了不同参数,以研究抗氧化活性、免疫反应、抗炎和抗凋亡活性。在存在 N-甲基-N'-硝基-N-亚硝基胍的情况下,丙二醛的水平显著升高,而在治疗大鼠中,超氧化物歧化酶和过氧化氢酶的抗氧化活性降低,与对照组相比。用 TEEO 干预胃癌诱导的大鼠,上调了氧化还原状态和免疫系统的活性,降低了癌症风险。MNNG 诱导的促炎细胞因子(IL-6 和 TNF-α)的分泌被 TEEO 显著抑制。TEEO 的给药还显著减少了末端脱氧核苷酸转移酶 dUTP 缺口末端标记阳性胃癌细胞、caspase-3 和 Bax 的 mRNA 表达,而 Bcl-2 的表达增加。此外,由于 TEEO,MNNG 诱导的大鼠胃组织中核因子 E2 相关因子 2(Nrf2)和血红素加氧酶-1(HO-1)以及 IκBα 降解和核因子-κB(NF-κB)p65 表达的下调明显升高。这表明 TEEO 通过发挥抗氧化应激、抗细胞凋亡反应、通过 Nrf2/HO-1 和 NF-κB 信号通路的抗炎反应,对 MNNG 诱导的胃癌具有保护作用。

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