Alyne Rodrigues de Araújo1, Bruno Iles2, Kerolayne de Melo Nogueira2, Jhones do Nascimento Dias3, Alexandra Plácido4, Artur Rodrigues5, Patrícia Albuquerque3, Ildinete Silva-Pereira3, Renato Socodatto5, Camila C Portugal5, João B Relvas5, Leiz Maria Costa Véras2, Filipe Camargo Dalmatti Alves Lima6, Augusto Batagin-Neto7, Jand-Venes Rolim Medeiros1, Paulo Humberto Moreira Nunes8, Peter Eaton9, José Roberto de Souza de Almeida Leite10. 1. The Northeast Biotechnology Network, RENORBIO, Federal University of Piaui, Teresina, PI, Brazil. 2. Biotechnology and Biodiversity Center Research, Biotec, Federal University of Piaui, Parnaíba, Piaui, Brazil. 3. Laboratory of Molecular Biology of Dimorphic and Pathogenic Fungi, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. 4. Glial Cell Biology Laboratory, Institute for Research and Innovation in Health, i3S, University of Porto, Porto, Portugal; Bioprospectum, Lda, UPTEC, Porto, Portugal. 5. Glial Cell Biology Laboratory, Institute for Research and Innovation in Health, i3S, University of Porto, Porto, Portugal. 6. Federal Institute of Education, Science and Technology of São Paulo, Campus Matão, Matão, Brazil. 7. São Paulo State Universit, UNESP, Campus of Itapeva, Itapeva, Brazil. 8. Medicinal Plants Research Center, NPPM, Federal University of Piaui, Teresina, Piaui, Brazil. 9. LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences of the University of Porto, Porto, Portugal. 10. The Northeast Biotechnology Network, RENORBIO, Federal University of Piaui, Teresina, PI, Brazil; Center for Research in Applied Morphology and Immunology, NuPMIA, University of Brasilia, Brasilia, Brazil. Electronic address: jrsaleite@gmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Folk knowledge transmitted between generations allows traditional populations to maintain the use of medicinal plants for the treatment of several diseases. In this context, the species Terminalia fagifolia Mart., native to Brazil, is used for the treatment of chronic and infectious diseases. Plants rich in secondary metabolites, such as this species and their derivatives, may represent therapeutic alternatives for the treatment of diseases that reduce the quality of life of people. AIM OF THE STUDY: The aim of this study was to evaluate the antifungal and anti-inflammatory potential of aqueous fraction from ethanolic extract of T. fagifolia, with in silico study of the major compound of the fraction. MATERIAL AND METHODS: The phytochemical study of the aqueous fraction was performed by HPLC, LC/MS and NMR. The antifungal activity was evaluated against yeasts, by determination of the minimum inhibitory concentration and minimum fungicidal concentration. The effect on Candida albicans was analyzed by AFM. The antibiofilm potential against biofilms of C. albicans was also tested. The anti-inflammatory potential of the aqueous fraction was evaluated in vivo by the carrageenan-induced paw edema and peritonitis. A microglial model of LPS-induced neuroinflammation was also studied. Further insights on the activation mechanism were studied using quantum chemistry computer simulations. Toxicity was evaluated in the Galleria mellonella and human erythrocytes models. RESULTS: Eschweilenol C was identified as the major constituent of the aqueous fraction of the ethanolic extract of T. fagifolia. The aqueous fraction was active against all Candida strains used (sensitive and resistant to Fluconazole) with MICs ranging from 1000 to 0.4 μg/mL. By AFM it was possible to observe morphological alterations in treated Candida cells. The fraction significantly (p < 0.05) inhibited paw edema and decreased levels of malondialdehyde induced by carrageenan. In a microglial cell model, aqueous fraction demonstrated the ability to inhibit NF-κB after induction with lipopolysaccharide. The theoretical studies showed structural similarity between eschweilenol C and indomethacin and an excellent antioxidant potential. The aqueous fraction did not present toxicity in the studied models. CONCLUSION: The results indicate that the aqueous fraction of T. fagifolia has potential for biomedical applications with low toxicity. This finding can be attributed to the predominance of eschweilenol C in the aqueous fraction.
ETHNOPHARMACOLOGICAL RELEVANCE: Folk knowledge transmitted between generations allows traditional populations to maintain the use of medicinal plants for the treatment of several diseases. In this context, the species Terminalia fagifolia Mart., native to Brazil, is used for the treatment of chronic and infectious diseases. Plants rich in secondary metabolites, such as this species and their derivatives, may represent therapeutic alternatives for the treatment of diseases that reduce the quality of life of people. AIM OF THE STUDY: The aim of this study was to evaluate the antifungal and anti-inflammatory potential of aqueous fraction from ethanolic extract of T. fagifolia, with in silico study of the major compound of the fraction. MATERIAL AND METHODS: The phytochemical study of the aqueous fraction was performed by HPLC, LC/MS and NMR. The antifungal activity was evaluated against yeasts, by determination of the minimum inhibitory concentration and minimum fungicidal concentration. The effect on Candida albicans was analyzed by AFM. The antibiofilm potential against biofilms of C. albicans was also tested. The anti-inflammatory potential of the aqueous fraction was evaluated in vivo by the carrageenan-induced paw edema and peritonitis. A microglial model of LPS-induced neuroinflammation was also studied. Further insights on the activation mechanism were studied using quantum chemistry computer simulations. Toxicity was evaluated in the Galleria mellonella and human erythrocytes models. RESULTS:Eschweilenol C was identified as the major constituent of the aqueous fraction of the ethanolic extract of T. fagifolia. The aqueous fraction was active against all Candida strains used (sensitive and resistant to Fluconazole) with MICs ranging from 1000 to 0.4 μg/mL. By AFM it was possible to observe morphological alterations in treated Candida cells. The fraction significantly (p < 0.05) inhibited paw edema and decreased levels of malondialdehyde induced by carrageenan. In a microglial cell model, aqueous fraction demonstrated the ability to inhibit NF-κB after induction with lipopolysaccharide. The theoretical studies showed structural similarity between eschweilenol C and indomethacin and an excellent antioxidant potential. The aqueous fraction did not present toxicity in the studied models. CONCLUSION: The results indicate that the aqueous fraction of T. fagifolia has potential for biomedical applications with low toxicity. This finding can be attributed to the predominance of eschweilenol C in the aqueous fraction.
Authors: Eder Alves Barbosa; Alexandra Plácido; Daniel C Moreira; Lucas Albuquerque; Anderson Dematei; Amandda É Silva-Carvalho; Wanessa F Cabral; Sonia N Báo; Felipe Saldanha-Araújo; Selma A S Kuckelhaus; Tatiana K Borges; Camila C Portugal; Renato Socodato; Cátia Teixeira; Filipe Camargo D A Lima; Augusto Batagin-Neto; Antônio Sebben; Peter Eaton; Paula Gomes; Guilherme D Brand; Joao B Relvas; Massuo J Kato; Jose Roberto S A Leite Journal: Proc Biol Sci Date: 2021-11-10 Impact factor: 5.349
Authors: Jhones do Nascimento Dias; Calliandra de Souza Silva; Alyne Rodrigues de Araújo; Jessica Maria Teles Souza; Paulo Henrique de Holanda Veloso Júnior; Wanessa Felix Cabral; Maria da Glória da Silva; Peter Eaton; José Roberto de Souza de Almeida Leite; André Moraes Nicola; Patrícia Albuquerque; Ildinete Silva-Pereira Journal: Sci Rep Date: 2020-06-25 Impact factor: 4.379
Authors: Alexandra Plácido; João Bueno; Eder A Barbosa; Daniel C Moreira; Jhones do Nascimento Dias; Wanessa Felix Cabral; Patrícia Albuquerque; Lucinda J Bessa; Jaime Freitas; Selma A S Kuckelhaus; Filipe C D A Lima; Augusto Batagin-Neto; Guilherme D Brand; João B Relvas; José Roberto S A Leite; Peter Eaton Journal: Biomolecules Date: 2020-03-27