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

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

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.

Keywords: Essential oils; Gastric cancer; Inflammation; MNNG; Oxidative stress; Tagetes erecta.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis
  • Catalase / metabolism
  • Cell Line, Tumor
  • Flowers* / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Guanidines
  • Heme Oxygenase (Decyclizing)* / metabolism
  • Immunoglobulin A / chemistry
  • Immunoglobulin G / chemistry
  • Immunoglobulin M / chemistry
  • Inflammation
  • Male
  • Methylnitronitrosoguanidine / chemistry
  • Mice
  • NF-E2-Related Factor 2
  • NF-KappaB Inhibitor alpha* / metabolism
  • Neoplasm Proteins* / metabolism
  • Nucleocytoplasmic Transport Proteins* / metabolism
  • Oils, Volatile / chemistry
  • Oxidative Stress / drug effects
  • Plant Extracts / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Stomach Neoplasms* / metabolism
  • Tagetes* / metabolism

Substances

  • Antioxidants
  • Catalase
  • Guanidines
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Methylnitronitrosoguanidine
  • Neoplasm Proteins
  • NF-KappaB Inhibitor alpha
  • Nfkbia protein, rat
  • nitroguanidine
  • Nucleocytoplasmic Transport Proteins
  • Oils, Volatile
  • p65 oncofetal mRNA transport protein, rat
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • NF-E2-Related Factor 2