title: In vitro effect of valepotriates isolated from Valeriana glechomifolia on rat P-type ATPases.
abstract: Valepotriates are iridoids found in variable amounts in Valerianaceae and might be among the bioactive compounds which confer anxiolytic properties to the Valeriana species. On the other hand, unspecific cytotoxicity has also been described. Presently, however, no particular molecular target has been defined for these compounds. Here we studied the effect of valtrate, acevaltrate, and 1- β-acevaltrate isolated from Valeriana glechomifolia on the enzymatic activity of rat P-type ATPases. Valepotriates did not affect rat skeletal muscle sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) activity at the highest concentration used (100 µM). In contrast, the same concentration inhibited roughly half of the total H⁺/K⁺-ATPase activity from rat gastric epithelium (valtrate 54.6 ± 3.2 %, acevaltrate 60.7 ± 7.3 %, 1- β-acevaltrate 50.2 ± 3.1 %; mean ± SEM, n = 3-5). Finally, these substances showed the highest inhibitory potency toward Na⁺/K⁺-ATPase, and the inhibition curves obtained provided a similar IC₅₀ (in µM) for rat kidney α1 isoform (valtrate 21.2, acevaltrate 22.8, 1- β-acevaltrate 24.4) and brain hemispheres α2/ α3 isoforms (valtrate 19.4, acevaltrate 42.3, 1- β-acevaltrate 38.3). Our results suggest that P-type ATPases are differentially inhibited by valepotriates and that Na⁺/K⁺-ATPase might be one of their molecular targets in vivo.
authors.affiliation: Laboratório de Farmacologia Bioquímica e Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Gustavo M
authors.initials: GM
authors.lastname: Bettero
authors.forename: Luisa
authors.initials: L
authors.lastname: Salles
authors.forename: Renata M
authors.initials: RM
authors.lastname: Rosário Figueira
authors.forename: Gilsane von
authors.initials: Gv
authors.lastname: Poser
authors.forename: Stela M K
authors.initials: SM
authors.lastname: Rates
authors.forename: François
authors.initials: F
authors.lastname: Noël
authors.forename: Luis Eduardo M
authors.initials: LE
authors.lastname: Quintas
authors.forename: Luis E M
authors.initials: LE
authors.lastname: Quintas
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D004848:Epithelium / Q000201:enzymology; D017506:H(+)-K(+)-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D020128:Inhibitory Concentration 50; D039823:Iridoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D013270:Stomach / Q000201:enzymology; D014632:Valerian / Q000737:chemistry*
chemical_list: D039823:Iridoids; C009643:valtrates (combination); D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; C030127:valtrate; C090810:acevaltrate