A cucurbitacin glycoside from Picrorhiza kurrooa

A novel cucurbitacin glycoside bitter principle has been isolated from roots extracts of Picrorhiza kurrooa and shown to be 25-acetoxy-2-β-glucosyloxy-3,16,20-trihydroxy-9-methyl-19-norlanosta-5,23-diene-22-one. Two previously described catalpol derivatives were also isolated; neither was as bitter as the cucurbitacin glycoside.     

A cytotoxic deoxocucurbitacin from Desfontainia spinosa

A new cytotoxic triterpene, 11-deoxocucurbitacin I was isolated from Desfontainia spinosa. The structure of this compound was elucidated by extensive analysis of the high field ¹H NMR and ¹³C NMR spectra and field desorption mass spectrometry. This is the first example of a cucurbitacin lacking an 11-keto functionality.     

Three new cucurbitane triterpenoids from Hemsleya penxianensis and their cytotoxic activities

Two new cucurbitane glycosides, hemslepenside A (1) and 16,25-O-diacetyl-cucurbitacin F-2-O-β-d-glucopyranoside (3), one new cucurbitacin, 16-O-acetyl-cucurbitacin F (2), along with three known cucurbitane compounds, were isolated from the roots of Hemsleya penxianensis. The structures of 1–6 were established on the basis of extensive spectroscopic and chemical methods. The isolated compounds were evaluated for their cytotoxic activities against different three human cancer cell lines, with IC₅₀ values in the low microgram range.     

Analgesic Effect of SH003 and Trichosanthes kirilowii Maximowicz in Paclitaxel-Induced Neuropathic Pain in Mice

Pacliatxel is a taxol-based chemotherapeutic drug that is widely used to treat cancer. However, it can also induce peripheral neuropathy, which limits its use. Although several drugs are prescribed to attenuate neuropathies, no optimal treatment is available. Thus, in our study, we analyzed whether SH003 and its sub-components could alleviate paclitaxel-induced neuropathic pain. Multiple paclitaxel injections (cumulative dose 8 mg/kg, i.p.) induced cold and mechanical allodynia from day 10 to day 21 after the first injection in mice. Oral administration of SH003, an herbal mixture extract of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz (Tk), dose-dependently attenuated both allodynia. However, when administered separately only Tk decreased both allodynia. The effect of Tk was shown to be mediated by the spinal noradrenergic system as intrathecal pretreatment with α₁- and α₂-adrenergic-receptor antagonists (prazosin and idazoxan), but not 5-HT_1/2, and 5-HT₃-receptor antagonists (methysergide and MDL-72222) blocked the effect of Tk. The spinal noradrenaline levels were also upregulated. Among the phytochemicals of Tk, cucurbitacin D was shown to play a major role, as 0.025 mg/kg (i.p.) of cucurbitacin D alleviated allodynia similar to 500 mg/kg of SH003. These results suggest that Tk should be considered when treating paclitaxel-induced neuropathic pain.     

Cucurbitacin E and I in Iberis amara: Feeding inhibitors for Phyllotreta nemorum

Cucurbitacin E and cucurbitacin I have been isolated from green parts of Iberis amara and identified by TLC, UV and MS. It is shown that cucurbitacins act as feeding inhibitors for the flea beetle Phyllotreta nemorum. The most potent feeding inhibitors in green parts of I. amara towards P. nemorum are cucurbitacin E and I, and the concentrations of these compounds in the plant are found to be high enough to prevent feeding of the flea beetle.     

A revision of the structure of cucurbitacin S from Bryonia dioica

¹H NMR studies at 400 MHz on cucurbitacin S and its derivatives suggest that the structure of cucurbitacin S previously isolated from Bryonia dioica should be revised from (22S)-22, 25-anhydro-2,16α,22,25-tetrahydroxy-3,11,23-trioxo-cucurbita-1,5-diene to (24S)-16,24-anhydro- 2,16α,24,25-tetrahydroxy-3,11,22-trioxo-cucurbita-1,5-diene.     

Gemins D,E and F,ellagitannins from Geum japonicum

Three new ellagitannins, gemin D, E and F were isolated from the leaves of Geum japonicum. The structures of gemin D and F were established as 3-O-galloyl-4,6-O-[(S-hexahydroxydiphenoyl]-D-glucose and 6-O-caffeoyl-2,3-O-[(S-hexahydroxydiphenoyl]-D-glucose, respectively. Gemin E is a novel C-glucosidic ellagitanin having a dehydrohexahydroxydiphenoyl group in the molecule. Gemin D was also isolated from the flower buds of Camellia japonica.     

Isolation and structure of cucurbitacin Q1

Cucurbitacin Q1, a compound isolated from the fruit of Cucumis prophetarum, has been shown to be the pure trans component of cucurbitacin Q.     

Grayanoside D,A diterpene glucoside from Leucothoe Grayana

A new diterpenoid glucoside, grayanoside D, has been isolated from Leucothoe grayana. Its structure was elucidated by chemical and spectroscopic means and by correlation with grayanotoxin-XV to be 3-O-(β-D-glucopyranosyl)-(10S)-dihydrograyanotoxin-XV.     

Isolation and structural elucidation of two new labdane diterpenoids from the aerial part of Roylea cinerea

Two new labdane diterpenoids, cinereanoid A (1) and cinereanoid B (2), along with five known compounds, calyone (3), pilloin (4), 1-methylindole-3-carboxaldehyde (5), β-sitosterol (6) and stigmasterol (7) were isolated from the aerial parts of Roylea cinerea (Lamiaceae). The new structures were determined by using IR, MS, 1D, 2D NMR spectroscopy. The structure of both new compounds was further confirmed by single crystal X-ray crystallographic analysis. In this study we have also reported single crystal X-ray structure of compound 3 which unambiguously confirmed the relative stereochemistry of tertiary hydroxyl and methyl groups, as it was not established by earlier report. Compounds 4 and 5 were isolated for the first time from this plant. In view of very few reports about this species, this report has increased the phytochemical knowledge about R. cinerea.     

Cucurbitacin I Induces Protective Autophagy in Glioblastoma in Vitro and in Vivo

There is an urgent need for new therapeutic avenues to improve the outcome of patients with glioblastoma multiforme (GBM). Current studies have suggested that cucurbitacin I, a natural selective inhibitor of JAK2/STAT3, has a potent anticancer effect on a variety of cancer cell types. This study showed that autophagy and apoptosis were induced by cucurbitacin I. Exposure of GBM cells to cucurbitacin I resulted in pronounced apoptotic cell death through activating bcl-2 family proteins. Cells treatment with cucurbitacin I up-regulated Beclin 1 and triggered autophagosome formation and accumulation as well as conversion of LC3I to LC3II. Activation of the AMP-activated protein kinase/mammalian target of rapamycin/p70S6K pathway, but not the PI3K/AKT pathway, occurred in autophagy induced by cucurbitacin I, which was accompanied by decreased hypoxia-inducible factor 1α. Stable overexpression of hypoxia-inducible factor 1α induced by FG-4497 prevented cucurbitacin I-induced autophagy and down-regulation of bcl-2. Knockdown of beclin 1 or treatment with the autophagy inhibitor 3-methyladenine also inhibited autophagy induced by cucurbitacin I. A coimmunoprecipitation assay showed that the interaction of Bcl-2 and Beclin 1/hVps34 decreased markedly in cells treated with cucurbitacin I. Furthermore, knockdown of beclin 1 or treatment with the lysosome inhibitor chloroquine sensitized cancer cells to cucurbitacin I-induced apoptosis. Finally, a xenograft model provided additional evidence for the occurrence of cucurbitacin I-induced apoptosis and autophagy in vitro. Our findings provide new insights into the molecular mechanisms underlying cucurbitacin I-mediated GBM cell death and may provide an efficacious therapy for patients harboring GBM.     

Cucurbitacin 19-hydroxylase in Cucurbita maxima

The enzymatic hydroxylation of the C-19-methyl group of cucurbitacin B and D was observed in partly purified preparations obtained from the unripe fruit of Cucurbita maxima. Assay methods were developed and the pH optimum, cofactor requirements, and substrate specificity determined.     

New flavonoids from the underground parts of Eriosema laurentii

Pharmacological, toxicological and phytochemical investigations of aerial parts of Eriosema laurentii De Wild. (Leguminosae), a plant used in traditional African medicine, showed a complex pattern of very rare and several new exceptional phenolic compounds. In continuation of the phytochemical work and based on the activity of an extract from the underground parts, the presented study showed the occurrence of a new pyranoisoflavone, named methyleriosemaone D, and a new highly prenylated (2S,3S)-6,8,3′-triprenyl-3,5,7,2′,4′-pentahydroxyflavanone in these parts of E. laurentii. In addition, the very rare pyranoisoflavone eriosemaone D was proven in this plant for the first time. All structures were elucidated unambiguously by extensive MS- and one and two-dimensional NMR-experiments. Detailed NMR spectra of eriosemaone D were included to rationalize the correction of some of the previously reported carbon signals in the ¹³C NMR spectrum. The estrogenic activity of the extract and isolated compounds was tested in an estrogen receptor α yeast transactivation assay.     

Norlignan glycosides from the leaves of Molineria latifolia

Two new norlignan glycosides, molinerioside D (5) and molinerioside E (9), were isolated from the methanol extract of fresh leaves of Molineria latifolia. Their structures were determined using spectroscopic evidence, such as 1D and 2D NMR and HR-ESI-MS studies. The structure of molinerioside D (5) was determined to be a norlignan glycoside with a C6-C5-C6 skeleton, while the structure of molinerioside E (9) was determined to be a glucosyl-fused norlignan derivative. In addition to the new compounds, twenty known compounds were found in the extract of M. latifolia fresh leaves.     

Identification and biological activity of secondary metabolites from Dryobalanops beccarii

A new trimeric oligostilbene, malaysianol D (1) and galloylglucoside, malaysin A (2), together with twelve known compounds (3–14) have been isolated from the methanol extract of the stem bark of Dryobalanops beccarii by combination of vacuum and radial chromatography techniques. Their structures were established on the basis of their spectroscopic evidence and comparison with the published data. The cytotoxic activity of isolated compounds was tested against A549 and MCF-7 cancer cell lines.     

Mrakia arctica sp. nov., a new psychrophilic yeast isolated from an ice island in the Canadian High Arctic

Two strains of a psychrophilic basidiomycetous yeast species belonging to the genus Mrakia were isolated from a melt-pool mat community, on an ice island located in Disraeli Fjord, Ellesmere Island in the Canadian Arctic. Analysis of the large subunit rDNA D1/D2 domain and internal transcribed spacer region sequences indicated that these strains represent a novel species, and the name Mrakia arctica sp. nov. is proposed. This new species could grow at sub-zero temperatures and in vitamin-free media. Moreover, lipase and cellulase enzymes of M. arctica were strongly active even at ?3 °C. These results suggest an important role for M. arctica in the biogeochemical cycle of glacial ecosystems.     

Istanbulin D and istanbulin E,two new sesquiterpene lactones from Smyrnium creticum

Two new sesquiterpene lactones, istanbulin D and istanbulin E, were isolated from the benzene and chloroform concentrates of Smyrnium creticum. The latter concentrate also yielded sitosterol and sitosteryl 3-β-d-glucoside. The structures of istanbulin D and E were assigned on the evidence of spectral methods.     

New potent P-glycoprotein modulators with the cucurbitane scaffold and their synergistic interaction with doxorubicin on resistant cancer cells

The novel cucurbitacins, balsaminagenin A and B (1–2) and balsaminoside A (3) and the know cucurbitacin karavelagenin C (4), together with five new mono or diacylated derivatives (5–9) of karavelagenin C were evaluated for multidrug resistance reversing activity on human MDR1 gene transfected mouse lymphoma cells. Compounds 2–6 exhibited a strong activity compared with that of the positive control, verapamil. Structure–activity relationships are discussed. Moreover, in the checkerboard model of combination chemotherapy, the interaction between doxorubicin and compounds 2–5 synergistically enhanced the effect of the anticancer drug. Compounds 1–4 were isolated from the aerial parts of Momordica balsamina L. The structures of the compounds were established on the basis of spectroscopic methods including 2D NMR experiments (COSY, HMQC, HMBC and NOESY).