Antitumour effect of odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway.

Oleandrigenin-3-O-ß-D-diginoside (a derivative of odoroside A), isolated and purified by our group, has seldom been explored for its pharmacological activity. This study aimed at clarifying the mechanisms towards the leukaemia-suppressive role of odoroside A (compound #1) and its derivative, oleandrigenin-3-O-ß-D-diginoside (compound #2) isolated from Nerium oleander. Viability and nuclear morphology change were assessed by CCK-8 assay and fluorescence microscope, respectively. Then, the cell apoptosis and autophagy induced by the compounds were detected by flow cytometry and Western blot. Xenograft model of nude mice was also applied to measure the leukaemia-suppressive effects of compound #2 in vivo. The result displayed that compound #1 and compound #2 inhibited the proliferation of HL60 and K562 cells and stronger effects were found in HL60 than K562 cells. Both of the compounds induced a dose-dependent apoptosis and autophagy in HL60 cells, where compound #2 was more potent than compound #1. Compound #2 also demonstrated a time-dependent apoptosis and autophagy in HL60 cells. Furthermore, ROS generation and JNK phosphorylation occurred in a dose-dependent manner in the cells treated with compound #2. Mitochondria also played critical role, proved by the decrease of Bcl-2, the release of cyto c to cytosol and the activation of caspase-3 and caspase-9. Moreover, the antitumour effects of compound #2 were validated in the nude mouse xenograft model in vivo. Odoroside A and its derivative inhibited the growth of leukaemia by inducing apoptosis and autophagy through the activation of ROS/JNK pathway. These results suggest that the compounds can serve as potential antitumour agents against leukaemia, especially acute myeloid leukaemia (AML).

Authentication of tejocote (Crataegus mexicana) dietary supplements based on DNA barcoding and chemical profiling.

Tejocote (Crataegus mexicana, Mexican hawthorn), known as a weight-loss supplement, has been marketed online and is easily available for overseas direct purchase. Alipotec (brand name) is known as one of the most popular products containing tejocote in Mexico and other countries. However, adverse effects have been reported by users of these supplements. Therefore it is necessary to find the reason for the side effect. Dietary supplement samples labelled as containing tejocote were analysed using mass spectrometry and DNA barcoding analysis. Our results demonstrate that Alipotec samples contained ingredients from different species, yellow oleander instead of tejocote. The rpoB barcode region was able to differentiate between tejocote and yellow oleander species. Moreover, it was also observed that three compounds, including thevetin B, neriifolin, and digitoxigenin, clearly distinguish between tejocote and yellow oleander samples. This is the first and preliminary investigation to use an integrated approach of both chemical and genomic profiling for the authentication of dietary supplement containing tejocote.

[Effect of griffithin on anticancer activity and apoptosis of cancer cells in vitro].

To study the anticancer activity of griffithin from Streptocaulon griffithii Hook. f. and its effect on apoptosis of cancer cells in vitro, the inhibitory effect of griffithin on cell proliferation was studied by MTT assay, the cell apoptosis was observed by AO/EB double decoration assay and flow cytometry. Griffithin exhibited high anticancer activity on four human cancer cell lines, with IC50 ranged from 0.17 - 0.43 microg x mL(-1). Griffithin also induced apoptosis of PC-3 cells. Griffithin had anticancer activity and induced apoptosis of cancer cells.

Antiproliferative cardenolides from Periploca graeca.

Nine cardiotonic steroids, six 17beta-cardenolides (2, 4, 6-9) and three 17alpha-cardenolides (1, 3, 5) have been identified from the chloroform and chloroform-methanol extracts of Periploca graeca L. (Asclepiadaceae) stems. Among these, compound 5, the 17alpha-isomer of periplocin 6, was identified as a new compound. The antiproliferative effects of these compounds were tested in vitro in the hormone-independent prostate cancer cell line PC-3. Five of these compounds, all 17beta-isomers with a 14beta-OH group and at least one sugar molecule (4, 6-9), showed a very strong antiproliferative effect, with IC50 values between 18 and 50 nM. Compound 2, the only 17beta-cardenolide aglycone, had an IC50 value of 0.6 microM, which is 13 to 16 times higher than the values found for the corresponding cardenolides with one or two sugars. The IC50 values found for the three 17alpha-isomers were significantly higher (5.4 and 7.3 microM), with IC50 ratios (17alpha-cardenolide/17beta-cardenolide) of up to 192. In the 17alpha-cardenolide series, the presence of a sugar unit does not seem to have a significant effect on the IC50 values. This is the first report showing a markedly different cytotoxicities between the 17alpha- and 17beta-isomers in the cardenolide series.

5alpha-cardenolides from Kanahia laniflora inhibit ionotropic acetylcholine receptors.

5alpha-cardenolides isolated from Kanahia laniflora are inhibitors of muscle-type nicotinic acetylcholine receptors expressed in TE671 cells with IC (50) values in the range of 27 - 60 microM, as determined by whole-cell patch-clamp electrophysiological experiments.

A rare cause of complete heart block after transdermal botanical treatment for psoriasis.

We report the case of a 59-year-old man with a new 3 degrees AV block with a history of psoriasis. After implantation of a definitive DDDR pacemaker, the patient reported a transdermal self-medication with an extract of Nerium oleander for the treatment of his psoriasis. The pharmacological, epidemiological, and clinical features are discussed in brief.

Anti-tumour activity of Digitalis purpurea L. subsp. heywoodii.

Recent research has shown the anticancer effects of digitalis compounds suggesting their possible use in medical oncology. Four extracts obtained from the leaves of Digitalis purpurea subsp. heywoodii have been assessed for cytotoxic activity against three human cancer cell lines, using the SRB assay. All of them showed high cytotoxicity, producing IC50 values in the 0.78 - 15 microg/mL range with the methanolic extract being the most active, in non toxic concentrations. Steroid glycosides (gitoxigenin derivatives) were detected in this methanolic extract. Gitoxigenin and gitoxin were evaluated in the SRB assay using the three human cancer cell lines, showing IC50 values in the 0.13 - 2.8 microM range, with the renal adenocarcinoma cancer cell line (TK-10) being the most sensitive one. Morphological apoptosis evaluation of the methanolic extract and both compounds on the TK-10 cell line showed that their cytotoxicity was mediated by an apoptotic effect. Finally, possible mechanisms involved in apoptosis induction by digitalis compounds are discussed.