title: How Natural Product Research has Contributed to Oral Care Product Development? A Critical View.
abstract: Despite the high number of studies on the biological effects of natural products (NP) and molecules isolated therefrom, only a small part of them reach the clinical phase and become commercially available. In this perspective we make an analysis on how plant research has impacted oral health care over the last 15 years.
  
  
  
  Sixteen major clinical trial registry databases across the globe were searched for completed randomized clinical trials of herbal/natural product interventions (RCTHI) in theperiod 2000-2015.
  
  
  
  There was a considerable increase in the number of RCTHI, which points out an interest of academia and industry in the development of novel NP-based therapeutics. There is a trendfor greater heterogeneity of targeted dental conditions, mostly oral mucositis, periodontitis and dental caries. Topical application rather than systemic use predominated in the dental scope as mouthwashes, toothpastes, oral patches and gels have been the most commonly tested pharmaceutical forms. Today, despite the high number of in vitro, in vivo and clinical studies testing NP and/or NP-isolated molecules, only 11% (n = 9) of them are phase IV clinical trials assessing commercially available herbal products. This may be a result of poorly designed, superficial basic research that does not provide evidence to support the clinical testing of NP and derived molecules.
  
  
  
  As of now, plant research is promising although still accounts for a modest participation in the oral health care industry due to limited investment and incomplete or inconsistent information from preclinical and clinical testing.
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas (UNICAMP), 901 Limeira Ave., 13414-018, Piracicaba, SP, Brazil.
authors.forename: Irlan Almeida
authors.identifier: 0000-0002-1079-6941
authors.initials: IA
authors.lastname: Freires
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas (UNICAMP), 901 Limeira Ave., 13414-018, Piracicaba, SP, Brazil. rosalen@fop.unicamp.br.
authors.forename: Pedro Luiz
authors.initials: PL
authors.lastname: Rosalen
mesh_terms: D000818:Animals; D004304:Dosage Forms; D004339:Drug Compounding; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D006801:Humans; D009059:Mouth Diseases / Q000517:prevention & control*; D009067:Mouthwashes / Q000627:therapeutic use*; D009909:Oral Health; D009910:Oral Hygiene / Q000379:methods*; D008517:Phytotherapy / Q000639:trends; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D010946:Plants, Medicinal; D013997:Time Factors; D014100:Toothpastes
chemical_list: D004304:Dosage Forms; D009067:Mouthwashes; D010936:Plant Extracts; D014100:Toothpastes
keywords: clinical trials; dentistry; natural products; oral health; plant research