The Syntheized Plant Metabolite 3,4,5-Tri-O-Galloylquinic Acid Methyl Ester Inhibits Calcium Oxalate Crystal Growth in a Drosophila Model, Downregulates Renal Cell Surface Annexin A1 Expression, and Decreases Crystal Adhesion to Cells

Autor(es)

El-Salam, Mohamed Abd ^{[1, 2, 3]} ; Bastos, Jairo Kenupp ^[2] ; Han, Jing Jing ^[3] ; Previdi, Daniel ^[4] ; Coelho, Eduardo B. ^[5] ; Donate, Paulo M. ^[4] ; Romero, Michael F. ^[1] ; Lieske, John ^[3]

Afiliação do(s) autor(es)

^[1] Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, Rochester, MN 55905 - USA

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Pharmaceut Sci, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Mayo Clin, Coll Med, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN 55905 - USA

^[4] Univ Sao Paulo, Fac Philosophy Arts & Sci, Dept Chem, BR-14040901 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Clin Med, BR-14040900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Medicinal Chemistry; v. 61, n. 4, p. 1609-1621, FEB 22 2018.
• Citações Web of Science: 2

Resumo

The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) model were investigated. Membrane, cytosolic, and total annexin A1 (AxA1), alpha-enolase, and heat shock protein 90 (HSP90) amounts were examined by Western blot analysis after subcellular fractionation, then confirmed by immunofluorescence staining of cultured cells. Pretreatment of MDCKI cells with TGAME for up to 6 h significantly diminished COM crystal binding in a concentration-dependent manner. TGAME significantly inhibited AxA1 surface expression by immunofluorescence microscopy, whereas intracellular AxA1 increased. Western blot analysis confirmed AxA1 expression changes in the membrane and cytosolic fractions compound-treated cells, whereas whole cell AxA1 remained unchanged. TGAME also significantly decreased the size, number, and growth of calcium oxalate (CaOx) crystals induced in a Drosophila melanogaster MT model and possessed a potent antioxidant activity in a DPPH assay. (AU)

• Processo FAPESP: 11/13630-7 - Validação química e farmacológica de extratos e princípios ativos de espécies de Copaifera
• Beneficiário: Jairo Kenupp Bastos
• Modalidade de apoio: Auxílio à Pesquisa - Temático