title: Anti-proliferative and anti-inflammatory effects of 3β,6β,16β-Trihydroxylup-20(29)-ene on cutaneous inflammation.
abstract: BACKGROUND
  3β,6β,16β-Trihydroxylup-20(29)-ene (TTHL) is a triterpene isolated from the flowers of Combretum leprosum, a plant used in folk medicine in the north of Brazil for the treatment of skin disorders.
  
  
  OBJECTIVE
  In the present study, TTHL was evaluated as a potential topical anti-inflammatory and anti-proliferative agent through in vivo and in vitro models.
  
  
  METHODS
  Anti-inflammmatory and anti-proliferative effects of TTHL were assessed using Swiss mice in acute and chronic models of skin inflammation induced by 12-O-tetradecanoylphorbol-acetate (TPA) application. Anti-proliferative activity was proved through in vitro experiments with the HaCaT human keratinocyte cell line.
  
  
  RESULTS
  Treatment with TTHL inhibited inflammatory parameters such as oedema formation and cellular infiltration in acute and chronic models. In the chronic model, TTHL also inhibited epidermal hyperproliferation, as evidenced by reduction of epidermis thickness and proliferating cell nuclear antigen expression. The anti-proliferative effect was confirmed by the capability of TTHL in reducing the proliferation and inducing cell apoptosis of HaCaT cells. Suggesting a mechanism of action, TTHL showed activation of corticosteroid receptors, but without the induction of corticosteroid-related cutaneous side effects.
  
  
  CONCLUSIONS
  Our results demonstrate consistent anti-inflammatory and anti-proliferative activity and assign TTHL as a valuable tool in the development of a new treatment for skin inflammatory and proliferative diseases, such as psoriasis.
authors.affiliation: Department of Pharmacology, Universidade Federal do Paraná, PO Box 19031, CEP 81530-900 Curitiba, Paraná, Brazil.
authors.forename: Cintia Delai da Silva
authors.initials: CD
authors.lastname: Horinouchi
authors.affiliation: Department of Pharmacology, Universidade Federal do Paraná, PO Box 19031, CEP 81530-900 Curitiba, Paraná, Brazil.
authors.forename: Daniel Augusto Gasparin Bueno
authors.initials: DA
authors.lastname: Mendes
authors.affiliation: Department of Pharmaceutical Sciences, Universidade Estadual de Ponta Grossa, Avenida Carlos Cavalcanti, 4748 (Room - M47), CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nolte
authors.affiliation: Department of Pharmaceutical Sciences, Universidade Estadual de Ponta Grossa, Avenida Carlos Cavalcanti, 4748 (Room - M47), CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Priscilla Salles de
authors.initials: PS
authors.lastname: Brito
authors.affiliation: Department of Pharmacology, Universidade Federal do Paraná, PO Box 19031, CEP 81530-900 Curitiba, Paraná, Brazil.
authors.forename: Bruna da Silva
authors.initials: BD
authors.lastname: Soley
authors.affiliation: Department of General Biology, Universidade Estadual de Ponta Grossa, Avenida Carlos Cavalcanti, 4748 CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Giovani Marino
authors.initials: GM
authors.lastname: Favero
authors.affiliation: Department of Chemistry, Universidade Federal de Rondônia, CEP 6801-974 Porto Velho, RO, Brazil.
authors.forename: Valdir Alves
authors.initials: VA
authors.lastname: Facundo
authors.affiliation: Department of Physiological Science, Universidade Federal de Santa Catarina, CEP 88040-900 Florianópolis, SC, Brazil.
authors.forename: Adair Roberto Soares
authors.initials: AR
authors.lastname: Santos
authors.affiliation: Department of Pharmacology, Universidade Federal do Paraná, PO Box 19031, CEP 81530-900 Curitiba, Paraná, Brazil.
authors.forename: Daniela de Almeida
authors.initials: DA
authors.lastname: Cabrini
authors.affiliation: Department of Pharmacology, Universidade Federal do Paraná, PO Box 19031, CEP 81530-900 Curitiba, Paraná, Brazil. Electronic address: otuki@ufpr.br.
authors.forename: Michel Fleith
authors.initials: MF
authors.lastname: Otuki
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002908:Chronic Disease; D003877:Dermatitis, Contact / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011565:Psoriasis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C510987:3beta,6beta,16beta-trihidroxilup-20(29)-ene; D000893:Anti-Inflammatory Agents; D006727:Hormone Antagonists; D018809:Proliferating Cell Nuclear Antigen; D011965:Receptors, Glucocorticoid; D014315:Triterpenes; D015735:Mifepristone; D013755:Tetradecanoylphorbol Acetate
keywords: Cell proliferation; Combretum leprosum; Inflammation; Psoriasis; Skin diseases; Triterpene