| In vitro: |
| Planta Med. 1981 Jan;41(1):21-8. | | Valepotriates, a new class of cytotoxic and antitumor agents.[Pubmed: 7232547 ] |
METHODS AND RESULTS:
The following Valepotriates: valtrate and didrovaltrate, isolated from the roots of VALERIANA WALLICHII D. C., as well as baldrinal, a degradation product of the valtrate, were tested for their cytotoxic and antitumor activities, respectively IN VITRO on cultured rat hepatoma cells (HTC line), and IN VIVO, on female mice KREBS II ascitic tumors.
CONCLUSIONS:
It appears that the three Valepotriates are very potent cytotoxic agents for the HTC hepatoma cells, and that the didrovaltrate induces a perceptible high per cent definitive remissions of the KREBS II ascitic tumors. | | Acta Pharmacol Sin . 2020 Jun;41(6):835-842. | | A novel derivative of valepotriate inhibits the PI3K/AKT pathway and causes Noxa-dependent apoptosis in human pancreatic cancer cells[Pubmed: 32047260] | | Abstract
Natural compound Valepotriate exhibits inhibitory activity against a number of cancers, but the effect of Valepotriate against pancreatic cancer is unclear, and the structure-activity relationship of Valepotriate has not been characterized. In this study, we performed a structure-based similarity search and found 16 hit compounds. Among the 16 hits, (1S,6S,7R)-6-(acetyloxy)-1-[(3-methylbutanoyl)oxy]-4a,5,6,7a-tetrahydro-1H-spiro[cyclopenta[c]pyran-7,2'-oxiran]-4-ylmethyl 3-methylbutanoate (denoted as Amcp) exhibited superior anticancer activity against human pancreatic cancer BxPC-3 and SW1990 cells. The anti-proliferation activity of Amcp was validated in human pancreatic cancer BxPC-3 and SW1990 cells in vitro. Amcp more effectively induced apoptosis in BxPC-3 and SW1990 cells than gemcitabine. At a concentration of 15 μM, Amcp significantly suppressed the PI3K/AKT pathway and disrupted the mitochondrial membrane equilibrium through modulation of Noxa and Mcl-1 balance in both cell lines. Meanwhile, knockdown of Noxa substantially attenuated Amcp-induced reduction of cell viability and anti-apoptotic protein Mcl-1 level in BxPC-3 cells. In addition, Amcp showed synergistic anticancer effects when combined with gemcitabine in BxPC-3 cells. To conclude, this work not only suggests that Amcp possesses a dual-inhibitory activity towards PI3K/AKT pathway and Mcl-1, but also enlightens further development of bioactive Valepotriate derivatives.
Keywords: Mcl-1; Noxa; PI3K/AKT; human pancreatic cancer; Valepotriate. | | Pharmacogn Mag . Jul-Sep 2017;13(51):512-516. | | Anti-epileptic Effects of Valepotriate Isolated from Valeriana jatamansi Jones and Its Possible Mechanisms[Pubmed: 28839381] | | Abstract
Objective: This work aimed to investigate the anti-epileptic effects of Valepotriate isolated from Valeriana jatamansi Jones and studied its possible mechanisms.
Methods: The anti-epileptic effects of Valepotriate were studied using maximal electroshock-induced seizure (MES), pentylenetetrazole (PTZ)-induced epilepsy, and pentobarbital sodium-induced sleeping model in mice. The possible anti-epileptic mechanisms of Valepotriate were investigated by analyzing the expressions of GABAA, GABAB, glutamic acid decarboxylase (GAD65), Bcl-2, and caspase-3 in the brain using Western blot assay.
Results: The results indicated that Valepotriate showed significant anti-epileptic activity against MES- and PTZ-induced epilepsy at doses of 5, 10, and 20 mg/kg, and ED50 values for MES- and PTZ-induced epilepsy were 7.84 and 7.19 mg/kg, respectively. Furthermore, Valepotriate (10 and 20 mg/kg) can significantly prolong sleeping time and shorten the latency time on the pentobarbital sodium-induced sleeping time test. Furthermore, Valepotriate (5, 10, and 20 mg/kg) could significantly up-regulate the expression of GABAA, GAD65, and Bcl-2 and down-regulate the expression of caspase-3, but had no significant effect on the expression of GABAB.
Conclusion: The results indicated that Valepotriate had anti-epileptic activity and the mechanisms might be associated with regulation of GABA and inhibition of neuronal apoptosis.
Summary: Anti-epileptic effect of Valepotriate was investigated for the 1st timeValepotriate showed notable anti-epileptic activityValepotriate can significantly increase the expression of GABAA, glutamic acid decarboxylase 65, and Bcl-2 and reduce the expression of caspase-3.
Keywords: Anti-epileptic; GABA; Valeriana jatamansi jones; apoptosis; Valepotriate. |
|
| In vivo: |
| Evid Based Complement Alternat Med. 2010 Jan 4. | | A Valepotriate Fraction of Valeriana glechomifolia Shows Sedative and Anxiolytic Properties and Impairs Recognition But Not Aversive Memory in Mice.[Pubmed: 20047889] | Plants of the genus Valeriana (Valerianaceae) are used in traditional medicine as a mild sedative, antispasmodic and tranquilizer in many countries.
METHODS AND RESULTS:
This study was undertaken to explore the neurobehavioral effects of systemic administration of a Valepotriate extract fraction of known quantitative composition of Valeriana glechomifolia (endemic of southern Brazil) in mice. Adult animals were treated with a single intraperitoneal injection of Valepotriate fraction (VF) in the concentrations of 1, 3 or 10 mg kg(-1), or with vehicle in the pre-training period before each behavioral test. During the exploration of an open field, mice treated with 10 mg kg(-1) of Valepotriate fraction showed reduced locomotion and exploratory behavior. Although overall habituation sessions for locomotion and exploratory behavior among vehicle control and doses of Valepotriate fraction were not affected, comparison between open-field and habituation sessions within each treatment showed that Valepotriate fraction administration at 1 and 10 mg kg(-1) impaired habituation. In the elevated plus-maze test, mice treated with Valepotriate fraction (10 mg kg(-1)) showed a significant increase in the percentage of time spent in the open arms without significant effects in the number of total arm entries. Valepotriate fraction at 3 mg kg(-1) produced an impairment of novel-object recognition memory. In contrast, Valepotriate fraction did not affect fear-related memory assessed in an inhibitory avoidance task.
CONCLUSIONS:
The results indicate that Valepotriate fraction can have sedative effects and affect behavioral parameters related to recognition memory. | | Phytother Res. 2002 Nov;16(7):650-4. | | Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study.[Pubmed: 12410546] | The aim of the present study was to carry out a controlled pilot study on the putative anxiolytic effect of Valepotriates.
METHODS AND RESULTS:
Thirty-six outpatients with generalized anxiety disorder (DSM III-R), after a 2-week wash-out, were randomized to one of the following three treatments for 4 weeks (n = 12 per group): Valepotriates (mean daily dose: 81.3 mg), diazepam (mean daily dose: 6.5 mg), or placebo. A parallel, double-blind, flexible-dose, placebo-controlled design was employed. No significant difference was observed among the three groups at baseline or in the change from baseline on the Hamilton anxiety scale (HAM-A) or in the trait part of the state-trait anxiety inventory (STAI-trait). Moreover, the three groups presented a significant reduction in the total HAM-A scores. On the other hand, only the diazepam and Valepotriates groups showed a significant reduction in the psychic factor of HAM-A. The diazepam group also presented a significant reduction of the STAI-trait.
CONCLUSIONS:
Although the principal analysis (HAM-A between group comparison) found negative results (probably due to the small sample size in each group), the preliminary data obtained in the present study suggest that the Valepotriates may have a potential anxiolytic effect on the psychic symptoms of anxiety.
However, since the number of subjects per group was very small, the present results must be viewed as preliminary.
Thus, further studies addressing this issue are warranted. |
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