title: Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats.
abstract: BACKGROUND
  Colon carcinogenesis is a multistep process and it emanates from a series of molecular and histopathological alterations. Glycyrrhizic acid (GA) is a natural and major pentacyclic triterpenoid glycoside of licorice roots extracts. It has several pharmacological and biological properties such as anti-inflammatory, anti-viral, and anti-cancer. In the present study, we investigated the chemopreventive potential of GA against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions i.e., aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats.
  
  
  METHODS
  Animals were divided into 5 groups. In group III, IV and V, GA was administered at the dose of 15 mg/kg b. wt. orally while in group II, III and IV, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b.wt once a week for first 5 weeks and animals were euthanized after 9 weeks.
  
  
  RESULTS
  GA supplementation suppressed the development of precancerous lesions and it also reduced the infiltration of mast cells, suppressed the immunostaining of Ki-67, NF-kB-p65, COX-2, iNOS and VEGF while enhanced the immunostaining of p53, connexin-43, caspase-9 and cleaved caspase-3. GA treatment significantly attenuated the level of TNF-α and it also reduced the depletion of the mucous layer as well as attenuated the shifting of sialomucin to sulphomucin.
  
  
  CONCLUSIONS
  Our findings suggest that GA has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of GA.
authors: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Jamia Hamdard Hamdard University, Hamdard Nagar, New Delhi, India.
authors: Rehan
authors: R
authors: Khan
authors: Abdul Quaiyoom
authors: AQ
authors: Khan
authors: Abdul
authors: A
authors: Lateef
authors: Muneeb U
authors: MU
authors: Rehman
authors: Mir
authors: M
authors: Tahir
authors: Farrah
authors: F
authors: Ali
authors: Oday O
authors: OO
authors: Hamiza
authors: Sarwat
authors: S
authors: Sultana
mesh_terms: D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018031:Connexin 43 / Q000032:analysis / Q000276:immunology; D004127:Dimethylhydrazines; D019695:Glycyrrhizic Acid / Q000627:therapeutic use*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009077:Mucins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D052116:Sialomucins / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D018031:Connexin 43; D004127:Dimethylhydrazines; D009077:Mucins; D052116:Sialomucins; D014409:Tumor Necrosis Factor-alpha; C012564:sulfomucin; D019695:Glycyrrhizic Acid