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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.

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.
AuthorsKalaiyarasu Thangaraj, Manju Vaiyapuri
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 96 Pg. 1253-1266 (Dec 2017) ISSN: 1950-6007 [Electronic] France
PMID29198745 (Publication Type: Journal Article)
CopyrightCopyright © 2017. Published by Elsevier Masson SAS.
Chemical References
  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cytokines
  • Flavones
  • Flavonoids
  • Glucosides
  • NF-kappa B
  • orientin
  • 1,2-Dimethylhydrazine
  • flavone
Topics
  • 1,2-Dimethylhydrazine (pharmacology)
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Antineoplastic Agents (pharmacology)
  • Biomarkers, Tumor (metabolism)
  • Carcinogenesis (drug effects, metabolism)
  • Cell Proliferation (drug effects)
  • Colon (drug effects, metabolism)
  • Colorectal Neoplasms (chemically induced, drug therapy, metabolism)
  • Cytokines (metabolism)
  • Flavones (pharmacology)
  • Flavonoids (pharmacology)
  • Glucosides (pharmacology)
  • Inflammation (drug therapy, metabolism)
  • Male
  • NF-kappa B (metabolism)
  • Rats
  • Rats, Wistar

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