PubMed · 906302
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A S Selivanova, K P Zelinskiĭ. 1977. [New preparations].. https://pubmed.ncbi.nlm.nih.gov/906302/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Malagashanine (MG) is the parent compound of a new type of indole alkaloids, the N(b)C(21)-secocuran, isolated so far from the Malagasy Strychnos species traditionally used as chloroquine adjuvants in the treatment of chronic malaria. Previously, it was shown to have weak in vitro intrinsic antiplasmodial activity (IC(50) = 146.5 +/- 0.2 microM), but did display marked in vitro chloroquine-potentiating action against the FcM29 chloroquine-resistant strain of Plasmodium falciparum. The purpose of the present study was to further investigate its reversal activity. Thus, the previous in vitro results were tested in vivo. The interaction of MG with several antimalarials against various strains of P. falciparum was also assessed. As expected, MG enhanced the effect of chloroquine against the resistant strain W2, but had no action on the susceptible strain 3D7 and two sensitive isolates. Interestingly, MG was found to exhibit significant chloroquine-potentiating action against the FcB1 strain formerly described as a resistant strain but one which has since lost its resistance for unknown reasons. One other relevant result that arose from our study was the observation of the selective enhancing action of MG on quinolines (chloroquine, quinine, and mefloquine), aminoacridines (quinacrine and pyronaridine), and a structurally unrelated drug (halofantrine), all of which are believed to exert their antimalarial effect by binding with haematin. MG was finally found to specifically act with chloroquine on the old trophozoite stage of the P. falciparum cycle. Similarities and differences between verapamil and MG reversal activity are briefly presented.
Chelerythrine, a natural benzophenanthridine alkaloid, has been reported to mediate a variety of biological activities, including inhibition of protein kinase C (PKC). Here we report that chelerythrine induced time- and dose-dependent activation of JNK1 and p38 in HeLa cells, which was mediated the upstream kinases, MEKK1 and MKK4. However, treatment with two other potent and selective PKC inhibitors, GF-109203X and Gö6983, or down-regulation of PKC activity by prolonged treatment with phorbol 12-myristate 13-acetate had no effect on JNK1 and p38 activities. Furthermore, under the conditions where JNK1 and p38 were activated, we did not observe any significant inhibitory effect of chelerythrine on the activities of PKC isozymes present in HeLa cells. Interestingly, pretreatment with the antioxidants, N-acetyl-L-cysteine, dithiothreitol, and glutathione, impaired chelerythrine-induced JNK1 and p38 activation. In addition, chelerythrine induced apoptosis that was blocked by the antioxidants and the dominant-negative mutants of MEKK1, MKK4, JNK1, and p38. Together, these results uncover a novel biochemical property of chelerythrine, i.e. activation of MEKK1- and MKK4-dependent JNK1 and p38 pathways through an oxidative stress mechanism, which mediate the induction of apoptosis, but are independent of PKC inhibition.
The present paper describes the development of a most simple, sensitive, and specific gas chromatographic method to date, for the direct determination of seven major bioactive isosteroidal alkaloids, namely ebeiedine, ebeiedinone, ebeienine, hupehenine, isoverticine, verticine, verticinone and imperialine, in Fritillaria species, a commonly used antitussive traditional Chinese medicinal (TCM) herb. In the present study, a commercially available Supelco SAC-5 capillary column (30 m x 0.25 mm, 0.25 microm) specifically designed for the analysis of steroids was utilized for the direct determination of Fritillaria alkaloids. Calibration curves were obtained by spiking authentic compounds and the internal standard (solanidine) into herbal samples prior to extraction. Extraction was conducted simply by shaking the pre-alkalized diethyl ether solution (5.0 ml) containing dried herb (0.1 g) for 2 h. All calibration curves showed good linear regressions (r2>0.995) within test ranges. The assay was reproducible and accurate with the overall intra- and inter-day variation and accuracy of less than 10% and more than 90%, respectively. The developed GC method was successfully utilized to analyze seven major bioactive alkaloids in seven Fritillaria species, and the results demonstrate that this direct GC analytical method is suitable for the quality control of this commonly used antitussive TCM herb.