Cintia Delai da Silva Horinouchi1, Daniel Augusto Gasparin Bueno Mendes1, Stefanie Nolte2, Priscilla Salles de Brito2, Bruna da Silva Soley1, Giovani Marino Favero3, Valdir Alves Facundo4, Adair Roberto Soares Santos5, Daniela de Almeida Cabrini1, Michel Fleith Otuki6. 1. Department of Pharmacology, Universidade Federal do Paraná, PO Box 19031, CEP 81530-900 Curitiba, Paraná, Brazil. 2. Department of Pharmaceutical Sciences, Universidade Estadual de Ponta Grossa, Avenida Carlos Cavalcanti, 4748 (Room - M47), CEP 84030-900 Ponta Grossa, Paraná, Brazil. 3. Department of General Biology, Universidade Estadual de Ponta Grossa, Avenida Carlos Cavalcanti, 4748 CEP 84030-900 Ponta Grossa, Paraná, Brazil. 4. Department of Chemistry, Universidade Federal de Rondônia, CEP 6801-974 Porto Velho, RO, Brazil. 5. Department of Physiological Science, Universidade Federal de Santa Catarina, CEP 88040-900 Florianópolis, SC, Brazil. 6. Department of Pharmacology, Universidade Federal do Paraná, PO Box 19031, CEP 81530-900 Curitiba, Paraná, Brazil. Electronic address: otuki@ufpr.br.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: In the present study, TTHL was evaluated as a potential topical anti-inflammatory and anti-proliferative agent through in vivo and in vitro models. MATERIAL AND 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. CONCLUSION: 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.
ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: In the present study, TTHL was evaluated as a potential topical anti-inflammatory and anti-proliferative agent through in vivo and in vitro models. MATERIAL AND 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. CONCLUSION: 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: Fernanda de Cássia Israel Cardoso; Priscila Peruzzo Apolinário; Jéssica da Silva Cunha Breder; Thalita Paranhos; Henrique Ceretta Oliveira; Ariane Dini Polidoro; Ana Railka Souza Oliveira Kumakura; Maria Helena Melo Lima Journal: Syst Rev Date: 2019-12-23