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Orientin, a C-glycosyl dietary flavone, suppresses colonic cell proliferation and mitigates NF-κB mediated inflammatory response in 1,2-dimethylhydrazine induced colorectal carcinogenesis

Biomed Pharmacother. 2017 Dec:96:1253-1266. doi: 10.1016/j.biopha.2017.11.088. Epub 2017 Dec 2.

Abstract

Orientin, a C-glycosyl dietary flavone profusely found in rooibos tea and passion fruit have gained much attention owing to their multiple pharmacological potentials. The present study intends to investigate the anti-proliferative and anti-inflammatory efficacy of Orientin in 1,2-dimethyl hydrazine (DMH) induced colorectal cancer (CRC) in rats. Animals were arbitrarily segmented into six groups and fed with high-fat diet. Group 1 served as control. Group 2 received weekly subcutaneous injections of DMH (20 mg/kg b.w.), for first 15 weeks. Group 3 administered with Orientin (10 mg/kg b.w., i.p.) whereas Groups 4-6 treated with Orientin in three phases, namely initiation (along with DMH), post-initiation (post-DMH injection) and entire period. Orientin ameliorates tumor marker levels significantly (p < 0.05) and reinstates the histological changes induced by DMH. The proliferative markers (PCNA and Ki67) were observed to be suppressed significantly (p < 0.05) in Orientin treated rats. Orientin abrogates (p < 0.05) the inflammatory mast cells and diminishes the expression of pro-inflammatory NF-κB and cytokines (TNF-α and IL-6). It also down-regulates over expression of inflammatory inducible enzymes (iNOS and COX-2) significantly (p < 0.05) and further substantiated by GLIDE XP and QPLD studies. Overall results promptly elucidate the anti-proliferative and anti-inflammatory efficacy of Orientin against CRC. Orientin can be developed as a promising chemotherapeutic agent, on further validation of other molecular mechanisms.

Keywords: 1,2-dimethylhydrazine; Cell proliferation; Colorectal cancer; Inflammation; Orientin.

MeSH terms

  • 1,2-Dimethylhydrazine / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / drug effects*
  • Carcinogenesis / metabolism
  • Cell Proliferation / drug effects*
  • Colon / drug effects
  • Colon / metabolism
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Cytokines / metabolism
  • Flavones / pharmacology*
  • Flavonoids / pharmacology*
  • Glucosides / pharmacology*
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Male
  • NF-kappa B / metabolism*
  • Rats
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cytokines
  • Flavones
  • Flavonoids
  • Glucosides
  • NF-kappa B
  • orientin
  • 1,2-Dimethylhydrazine
  • flavone