title: An ex vivo evaluation of the efficacy of andrographolide in modulating differential expression of transcription factors and target genes in periodontal cells and its potential role in treating periodontal diseases.
abstract: CONCLUSIONS
  Andrographolide is a herbal extract traditionally used in South Asian countries for treating inflammatory diseases.
  
  
  OBJECTIVE
  To evaluate the efficacy of andrographolide in management of periodontal disease which is a highly prevalent oral disease.
  
  
  METHODS
  Periodontal ligament fibroblasts (PDLF) were cultured from healthy and diseased periodontium using explant culture methods. The safe dose of AG was determined using MTT assay. LPS (lipopolysaccharide) of the most important periodontopathogen, P gingivalis was used to activate NF-κB and STAT3 in PDLF. The efficacy of AG in inhibiting NF-κB and STAT3 was analyzed using immunofluorescence. Down regulation of expression of target genes of these transcription factors related to inflammation and bone resorption were analyzed using real time PCR.
  
  
  RESULTS
  AG up to the concentration of 25μM was found to be safe as determined by MTT assay. Statistically significant activation of NF-κB and STAT3 in cultured PDLF was observed in diseased group compared to healthy controls before and after LPS challenge. 5μM AG pretreatment significantly inhibited activation of NF-κB and STAT3 and down regulated expression of inflammatory and bone resorptive genes in cultured PDLF.
  
  
  CONCLUSIONS
  The findings of the present study propose the adjunctive use of a novel herbal drug andrographolide as a promising host modulation agent for periodontal therapy by inhibiting NF-κB and STAT3 activation and inhibition of inflammation and bone resorption related genes.
authors.affiliation: PMS College of Dental Sciences and Research, Trivandrum 695028, Kerala, India. Electronic address: ambiliranjith@yahoo.com.
authors.lastname: Ambili R
authors.affiliation: Government Dental College, Trivandrum 695011, Kerala, India.
authors.forename: Prasanthila
authors.initials: P
authors.lastname: Janam
authors.affiliation: Rajiv Gandhi Centre for Biotechnology (RGCB), Poojappura, Thiruvananthapuram 695014, Kerala, India.
authors.forename: P S
authors.initials: PS
authors.lastname: Saneesh Babu
authors.affiliation: Rajiv Gandhi Centre for Biotechnology (RGCB), Poojappura, Thiruvananthapuram 695014, Kerala, India.
authors.forename: Manu
authors.initials: M
authors.lastname: Prasad
authors.affiliation: Tissue Culture Laboratory, Sree Chitra Thirunal Institute for Medical Sciences and Technology (SCTIMST), Biomedical Technology Wing, Poojapura 695012, Thiruvananthapuram, India.
authors.forename: D
authors.initials: D
authors.lastname: Vinod
authors.affiliation: Tissue Culture Laboratory, Sree Chitra Thirunal Institute for Medical Sciences and Technology (SCTIMST), Biomedical Technology Wing, Poojapura 695012, Thiruvananthapuram, India.
authors.forename: P R
authors.initials: PR
authors.lastname: Anil Kumar
authors.affiliation: Tissue Culture Laboratory, Sree Chitra Thirunal Institute for Medical Sciences and Technology (SCTIMST), Biomedical Technology Wing, Poojapura 695012, Thiruvananthapuram, India.
authors.forename: T V
authors.initials: TV
authors.lastname: Kumary
authors.affiliation: Rajiv Gandhi Centre for Biotechnology (RGCB), Poojappura, Thiruvananthapuram 695014, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Asha Nair
authors.affiliation: Rajiv Gandhi Centre for Biotechnology (RGCB), Poojappura, Thiruvananthapuram 695014, Kerala, India.
authors.forename: M
authors.initials: M
authors.lastname: Radhakrishna Pillai
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D008070:Lipopolysaccharides; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010510:Periodontal Diseases / Q000188:drug therapy / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology; D053245:RANK Ligand / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053245:RANK Ligand; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C505688:TNFSF11 protein, human; C030419:andrographolide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Andrographolide; Andrographolide (PubChem CID: 5318517); Host modulation therapy; NF-κB and STAT3; Periodontitis; Transcription factor