title: The effects of a novel botanical agent on lipopolysaccharide-induced alveolar bone loss in rats.
abstract: BACKGROUND
  The development of host-modulatory agents with low risk of adverse effects has been needed to treat periodontitis, a chronic inflammatory disease. A botanical mixture of extracts from two natural substances, Panax notoginseng and Rehmannia glutinosa Libosch, was developed as a novel botanical agent synthesized with anti-inflammatory effect. The aim of this study is to evaluate the effects of the botanical mixture on the release of inflammatory cytokines and its inhibitory effect on lipopolysaccharide (LPS)-induced alveolar bone loss (ABL) in a rat model.
  
  
  METHODS
  Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-5(3-carboxymethoxyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay using human gingival fibroblast (hGF) and human periodontal ligament (hPDL) cells. Human acute monocytic leukemia cell line and hGF cells were cultured to assay tumor necrosis factor (TNF)-α and interleukin (IL)-6, respectively. Microcomputed tomography analysis and immunofluoresence analysis were performed to evaluate the efficacy of the botanical mixture to inhibit the destruction of alveolar bone and connective tissue in a rat model.
  
  
  RESULTS
  The botanical mixture is cytotoxic at concentrations exceeding 2.5 mg/mL (P <0.05). Based on the results from cytotoxicity assay, it can be determined that the pharmacologic ranges of the botanical mixture to be used in all subsequent in vitro and in vivo experiments. The botanical mixture reduced the release of TNF-α and IL-6 from human monocytic cells and hGF cells in a dose-dependent manner (P <0.05). The administration of the botanical mixture significantly reduced the alveolar bone loss in a rat model (P <0.05). In groups treated with the botanical mixture, matrix metalloproteinase (MMP)-9 was detected along the alveolar bone crest (ABC), but not around the gingival connective tissue, while in the group with LPS-induced ABL, pronounced expression of MMP-9 around the ABC, periodontal ligament, and gingival connective tissue was found.
  
  
  CONCLUSIONS
  The botanical mixture showed a potential adjunctive effect in the treatment of periodontitis. However, the present findings are obtained in vitro and in a rat model, so further clinical study is needed for its clinical application.
authors.affiliation: Dental Research Institute, School of Dentistry, 2nd Stage of Brain Korea 21 Project for School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Bo-Ah
authors.initials: BA
authors.lastname: Lee
authors.forename: Hwa-Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Jung
authors.forename: Se-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Yong-Wook
authors.initials: YW
authors.lastname: Lee
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Chang
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Chung
authors.forename: Ok-Su
authors.initials: OS
authors.lastname: Kim
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000539:Alveolar Process / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use* / Q000633:toxicity; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003238:Connective Tissue / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use / Q000633:toxicity; D004926:Escherichia coli; D005347:Fibroblasts / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010513:Periodontal Ligament / Q000187:drug effects; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000627:therapeutic use* / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D032267:Rehmannia; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; D008070:Lipopolysaccharides; C519374:Panax notoginseng extract; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat