Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration.
Natural products are important sources of chemical diversity leading to unique scaffolds that can be exploited in the discovery of new drug candidates or chemical probes. In this context, chemical and biological investigation of ferns and lycophytes occurring in Brazil is an approach adopted by our research group aiming at discovering bioactive molecules acting on neurodegeneration targets. In the present study, rosmarinic acid (RA) isolated from Blechnum brasiliense showed an in vitro multifunctional profile characterized by antioxidant effects, and monoamine oxidases (MAO-A and MAO-B) and catechol-O-methyl transferase (COMT) inhibition. RA showed antioxidant effects against hydroxyl (HO(•)) and nitric oxide (NO) radicals (IC50 of 29.4 and 140 μM, respectively), and inhibition of lipid peroxidation (IC50 of 19.6 μM). In addition, RA inhibited MAO-A, MAO-B and COMT enzymes with IC50 values of 50.1, 184.6 and 26.7 μM, respectively. The MAO-A modulation showed a non-time-dependent profile, suggesting a reversible mechanism of inhibition. Structural insights on RA interactions with MAO-A and COMT were investigated by molecular docking. Finally, RA (up to 5 mM) demonstrated no cytotoxicity on polymorphonuclear rat cells. Taken together, our results suggest that RA may be exploited as a template for the development of new antioxidant molecules possessing additional MAO and COMT inhibition effects to be further investigated on in vitro and in vivo models of neurodegenerative diseases.
Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, 90.610-000, Porto Alegre, RS, Brazil. Electronic address: juandradep@gmail.com.
Juliana Maria de Mello
JM
Andrade
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211, Geneva 4, Switzerland.
Carolina
C
Dos Santos Passos
School of Application, UFRGS, Av. Bento Gonçalves, 9500, 91.501-970, Porto Alegre, RS, Brazil.
Maria Angélica
MA
Kieling Rubio
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Av. do Café s/no, 14.040-903, Ribeirão Preto, SP, Brazil.
Jacqueline Nakau
JN
Mendonça
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (USP), Av. do Café s/no, 14.040-903, Ribeirão Preto, SP, Brazil.
Norberto Peporine
NP
Lopes
Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, 90.610-000, Porto Alegre, RS, Brazil.
Amélia Teresinha
AT
Henriques
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D002394:Catechol O-Methyltransferase / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D053630:Depsides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D029624:Ferns / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D017665:Hydroxyl Radical / Q000737:chemistry / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D000097123:Rosmarinic Acid
D000975:Antioxidants; D002394:Catechol O-Methyltransferase; D002934:Cinnamates; D053630:Depsides; D006861:Hydrogen Peroxide; D017665:Hydroxyl Radical; D008995:Monoamine Oxidase; D009569:Nitric Oxide; D000097123:Rosmarinic Acid
Antioxidant; Blechnum brasiliense; COMT; MAO-A; Molecular docking; Rosmarinic acid