Disease relevance of Helixin

• This study investigated the effects of alpha-hederin on the regulation of MT expression in an in vitro model using the murine hepatoma cell line, Hepa-1c1c7, and the murine macrophage cell line, RAW 264 [1].
• In this study we observed that alpha-hederin caused a dose- and time-dependent increase in apoptosis of murine leukemia P388 cells [2].
• alpha-Hederin, a pentacyclic triterpene saponin isolated from the seeds of Nigella sativa, was recently reported to have potent in vivo antitumor activity against LL/2 (Lewis Lung carcinoma) in BDF1 mice [2].
• The administration of alpha-hederin, an inducer of metallothionein, results in a secondary zinc deficiency that may be an important maternally mediated mechanism of developmental toxicity [3].
• A single dose of alpha-hederin, injected sc at dosages of 3 to 300 mumol/kg, caused an acute phase response, indicated by decreased Fe and Zn, and increased Cu, alpha 1-acid glycoprotein, and ceruloplasmin concentration in plasma, along with a dosage-related increase in maternal hepatic MT concentration [4].

High impact information on Helixin

• Involvement of cytokines in the hepatic metallothionein expression by alpha-hederin [1].
• These results suggest that the upregulation of MT expression by alpha-hederin is mediated by TNF-alpha and IL-6 [1].
• The antioxidant activities of alpha-hederin and hederasaponin-C from Hedera helix, and hederacolchisides-E and -F from Hedera colchica were investigated, in this study [5].
• These results demonstrate that alpha-hederin stimulates NO release and is able to upregulate iNOS expression through NF-kappa B transactivation, which may be a mechanism, whereby alpha-hederin elicits its biological effects [6].
• Transient expression assays with NF-kappa B binding sites linked to the luciferase gene revealed that the increased level of iNOS mRNA induced by alpha-hederin was mediated by the NF-kappa B transcription factor complex [6].

Chemical compound and disease context of Helixin

• However, Lactobacillus sp. and Streptococcus sp. transformed KPK to KPI, KPA, and hederagenin only via KPJ [7].
• The anti-inflammatory potential of alpha-hederin (monodesmoside) and hederasaponin-C from Hedera helix, and hederacolchisides-E and -F (bidesmosides) from H. colchica was investigated in carrageenan-induced acute paw edema in rats [8].
• Bacteroides sp., and Bifidobacterium sp. and Fusobacterium sp. transformed KPK to KPI and KPA and hederagenin via KPH or KPJ [7].

Biological context of Helixin

• In this study, we examine the effects of alpha-hederin on the release of nitric oxide (NO) and the level of inducible nitric oxide synthase (iNOS) gene expression in mouse macrophages. alpha-Hederin elicited a dose-dependent increase in NO secretion [6].
• Its cytotoxicity decreases in the presence of serum in which BSA seems to be able to bind the saponin. alpha-Hederin also induces vacuolization of the cytoplasm and membrane alterations leading to cell death [9].
• Oleanolic acid, alpha-hederin hydrate, and betulic acid inhibited the chitin synthase II activity under the same conditions with an IC50 of 5.6, 64.3, and 98.7 micrograms/ml, respectively [10].
• So, the membrane-perforating properties associated with saponins, here represented by alpha-hederin, enhance neither cytotoxicity nor apoptosis of these cancer cells [11].
• Previous studies have shown adverse developmental outcome with a single administration of alpha-hederin to rats on gestation day (GD) 8 or 11 [3].

Anatomical context of Helixin

• Our results indicate that, in a serum-free medium, alpha-hederin is cytotoxic and inhibits proliferation in both cell lines at rather low concentrations (< 5 micrograms/ml) after only 8 hours of treatment [9].
• Expression of inducible nitric oxide synthase by alpha-hederin in macrophages [6].
• Effects of alpha-hederin, a saponin extracted from Hedera helix, on cells cultured in vitro [9].
• To examine the role of P450 in hepatoprotection by alpha-hederin, liver microsomes were prepared 24 hr following the last dose of alpha-hederin treatment (10 and 30 mumol/kg, sc x 3 days) [12].
• Following an oral pulse of 65Zn subsequent to treatment with 0 or 20 mumol/kg of alpha-hederin, the distribution of 65Zn to the liver of treated dams was twice that of controls, whereas the radiolabeled zinc apportioned to the decidua and uterus decreased by 44% [3].

Associations of Helixin with other chemical compounds

• Antileishmanial activity of three saponins isolated from ivy, alpha-hederin, beta-hederin and hederacolchiside A1, as compared to their action on mammalian cells cultured in vitro [13].
• Two new triterpenoid saponins, tanguticoside A and B along with seven known saponins vitalboside B, alpha-hederin, saponin PK, beta-hederin, saponin PJ3, saponin PE, and ciwujianoside A were isolated from aerial part of Clematis tangutica [14].
• An unusual case of death: suffocation caused by leaves of common ivy (Hedera helix). Detection of hederacoside C, alpha-hederin, and hederagenin by LC-EI/MS-MS [15].
• Modes of action of alpha-hederin and thymoquinone, active constituents of Nigella sativa, against HEp-2 cancer cells [16].
• Intracellular glutathione depletion and reactive oxygen species generation are important in alpha-hederin-induced apoptosis of P388 cells [2].

Gene context of Helixin

• Induction of metallothionein by alpha-hederin [17].
• Thus, this study suggests that kalopanaxsaponin A-mediated inhibition of iNOS, COX-2 expression, and TNF-alpha release may be one of the mechanisms responsible for the anti-inflammatory effects of the stem bark of Kalopanax pictus Nakai [18].
• Highly haemolytic saponins such as alpha-hederin and beta-escine showed partial (60%) inhibition of radioligand-binding to the ETA receptor and complete inhibition (100%) to the AT1 receptor [19].
• These results suggest that the suppressive effect of alpha-Hederin on TCDD-induced Cyp1a-1 gene expression in Hepa-1c1c7 cells might be an antagonist of the DNA binding potential of a nuclear Ah receptor [20].
• Electrophoretic mobility shift assay using nuclear extraction of cells revealed that alpha-Hederin reduced transformation of the Ah receptor to a form capable of specifically binding to an oligonucleotide containing a dioxin-response element (DRE) sequence of the Cyp1a-1 gene [20].

Analytical, diagnostic and therapeutic context of Helixin

• In the alpha-hederin-exposed RAW 264.7 cell cultures, production and mRNA levels of TNF-alpha and IL-6 were increased [1].
• Zn distribution was evaluated by giving an oral pulse of 65Zn 8 h after treatment with 0, 30, or 300 mumol/kg alpha-hederin on gestation day 11, and measuring 65Zn levels 18 h after treatment [4].
• Levels of mRNA of P4501A1/2 and P4502B1/2 were also decreased by alpha-Hederin as shown by Northern blot analysis [21].
• Transmission electron microscopy observations indicated that compared with untreated control yeasts, alpha-hederin induced modifications of cellular contents and alterations of cell envelope with degradation and death of the yeasts [22].
• The method involved a solid phase extraction of GLY, GA, and alpha-hederin, the internal standard (IS), from plasma with Waters Oasis MCX solid phase extraction (SPE) cartridges (30 mg) and a detection using a Micromass Quattro LC liquid chromatography/tandem mass spectrometry system with electrospray ionization source in positive ion mode [23].

References