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

被引:22
作者
Ambili, R. [1 ]
Janam, Prasanthila [2 ]
Babu, P. S. Saneesh [3 ]
Prasad, Mama. [3 ]
Vinod, D. [4 ]
Kumar, P. R. Anil [4 ]
Kumary, T. V. [4 ]
Nair, S. Asha [3 ]
Pillai, M. Radhakrishna [3 ]
机构
[1] PMS Coll Dent Sci & Res, Trivandrum 695028, Kerala, India
[2] Govt Dent Coll, Trivandrum 695011, Kerala, India
[3] RGCB, Thiruvananthapuram 695014, Kerala, India
[4] SCTIMST, Tissue Culture Lab, Biomed Technol Wing, Thiruvananthapuram 695012, Kerala, India
关键词
NF-kappa B and STAT3; Transcription factor; Host modulation therapy; Periodontitis; Andrographolide; FACTOR-KAPPA-B; LIGAMENT FIBROBLASTS; STAT3; OSTEOCLASTOGENESIS; INHIBITION; ACTIVATION; PATHWAYS; PATHOGENESIS; INFLAMMATION; SUPPRESSION;
D O I
10.1016/j.jep.2016.12.029
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Ethanopharmacological relevance: Andrographolide is a herbal extract traditionally used in South Asian countries for treating inflammatory diseases. Aim of the study: To evaluate the efficacy of andrographolide in management of periodontal disease which is a highly prevalent oral disease. Materials and Methods: Periodontal ligament fibroblasts (PDLF) were cultured from healthy and diseased periodontium using explant culture methods. The safe dose of AG was determined using MIT assay. LPS (lipopolysaccharide) of the most important periodontopathogen, P gingivalis was used to activate NF-kappa B and STAT3 in PDLF. The efficacy of AG in inhibiting NF-kappa B 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 25 mu M was found to be safe as determined by MIT assay. Statistically significant activation of NF-kappa B and STAT3 in cultured PDLF was observed in diseased group compared to healthy controls before and after LPS challenge. 5 mu M AG pretreatment significantly inhibited activation of NF-kappa B 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-kappa B and STAT3 activation and inhibition of inflammation and bone resorption related genes.
引用
收藏
页码:160 / 167
页数:8
相关论文
共 52 条
[31]   Discovery and development of Toll-like receptor 4 (TLR4) antagonists: A new paradigm for treating sepsis and other diseases [J].
Leon, Carlos G. ;
Tory, Rita ;
Jia, Jessica ;
Sivak, Olena ;
Wasan, Kishor M. .
PHARMACEUTICAL RESEARCH, 2008, 25 (08) :1751-1761
[32]   What does Stat3 do? [J].
Levy, DE ;
Lee, CK .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (09) :1143-1148
[33]   Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis [J].
Mao, Song ;
Park, Yoonsuk ;
Hasegawa, Yoshiaki ;
Tribble, Gena D. ;
James, Chloe E. ;
Handfield, Martin ;
Stavropoulos, M. Franci ;
Yilmaz, Ozlem ;
Lamont, Richard J. .
CELLULAR MICROBIOLOGY, 2007, 9 (08) :1997-2007
[34]   MESENCHYMAL STEM CELLS ISOLATED FROM HUMAN PERIODONTAL LIGAMENT [J].
Miletic, Maja ;
Mojsilovic, S. ;
Okic-Dordevic, Ivana ;
Kukolj, Tamara ;
Jaukovic, Aleksandra ;
Santibanez, J. F. ;
Jovcic, Gordana ;
Bugarski, Diana .
ARCHIVES OF BIOLOGICAL SCIENCES, 2014, 66 (01) :261-271
[35]   Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010 [J].
Newman, David J. ;
Cragg, Gordon M. .
JOURNAL OF NATURAL PRODUCTS, 2012, 75 (03) :311-335
[36]  
Newman M. G., 2011, ELSEVIER HLTH S 0214
[37]   Endocannabinoids and Inflammatory Response in Periodontal Ligament Cells [J].
Ozdemir, Burcu ;
Shi, Bin ;
Bantleon, Hans Peter ;
Moritz, Andreas ;
Rausch-Fan, Xiaohui ;
Andrukhov, Oleh .
PLOS ONE, 2014, 9 (09)
[38]   Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions [J].
Page, RC ;
Offenbacher, S ;
Schroeder, HE ;
Seymour, GJ ;
Kornman, KS .
PERIODONTOLOGY 2000, 1997, 14 :216-248
[39]   Activators and target genes of Rel/NF-κB transcription factors [J].
Pahl, HL .
ONCOGENE, 1999, 18 (49) :6853-6866
[40]   Activation of nuclear factor-κB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes [J].
Romeo, G ;
Liu, WL ;
Asnaghi, V ;
Kern, TS ;
Lorenzi, M .
DIABETES, 2002, 51 (07) :2241-2248