| Description: |
Acevaltrate displays high cytotoxicity against GLC(4), a human small-cell lung cancer cell line, and against COLO 320, a human colorectal cancer cell line, with IC50 values of 1-6 uM. Acevaltrate inhibits the Na+/K+-ATPase activity in the rat kidney and brain hemispheres with IC50s of 22.8±1.1 μM and 42.3±1.0 μM, respectively. |
| In vitro: |
| Planta Med. 2011 Oct;77(15):1702-6. | | In vitro effect of valepotriates isolated from Valeriana glechomifolia on rat P-type ATPases.[Pubmed: 21567360 ] | 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.
METHODS AND RESULTS:
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).
CONCLUSIONS:
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. | | Phytomedicine. 1998 May;5(3):219-25. | | Cytotoxic potential of valerian constituents and valerian tinctures.[Pubmed: 23195845 ] | Underground parts of three Valeriana species, namely V. officinalis L. s.l., V. wallichii DC. (V. jatamansi Jones), and V. edulis Nutt. ex Torr & Gray ssp. procera (H.B.K.) F. G. Meyer (V. mexicana DC.), are used in phytotherapy because of their mild sedative properties.
METHODS AND RESULTS:
Characteristic constituents of these species, which are regarded also as the active principles, were tested for cytotoxicity against GLC(4), a human small-cell lung cancer cell line, and against COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. Valepotriates of the diene type (valtrate, isovaltrate and Acevaltrate) displayed the highest cytotoxicity, with IC50 values of 1-6 μM, following continuous incubation.
CONCLUSIONS:
The monoene type valepotriates (didrovaltrate and isovaleroxyhydroxydidrovaltrate) were 2- to 3-fold less toxic. Baldrinal and homobaldrinal, decomposition products of valepotriates, were 10- to 30-fold less toxic than their parent compounds. Isovaltral had a higher cytotoxicity than its parent compound isovaltrate. |
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