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PubMed2005

Natural compounds derived from foods modulate nitric oxide production and oxidative status in epithelial lung cells.

The effects of natural antioxidants on nitric oxide (NO) modulation and oxidative status were determined in rat epithelial lung cells (L-2). Cells were stimulated with cytokines and treated with one of the following: resveratrol, soybean saponin group B (SSB), quercetin, genistein, olive leaf polyphenol concentrate (OLPC), or N-acetyl-L-cystein (NAC). NAC had no effect on NO levels, whereas resveratrol and OLPC were found to be effective in reducing nitrite levels, modifying iNOS mRNA, and decreasing free radical production. OLPC affected the levels of MnSOD while resveratrol did not, indicating that they act via different pathways. Quercetin and genistein reduced nitrite levels without affecting iNOS levels, presumably by scavenging NO. SSB did not affect nitrite levels, but exposure did reduce iNOS mRNA expression and protein levels, possibly due to antioxidant activity. Naturally occurring antioxidants, in particular resveratrol and OLPC, may have therapeutic potential in the treatment of inflammatory diseases.

Animals↗
PubMed1996

[Plasma-desorption mass spectrometry of natural compounds. 1. Basic properties of the method and its use for analyzing proteins and peptides].

Applications of plasma desorption mass spectrometry (PD MS) to the analysis of natural substances are reviewed with the special emphasis on its use in peptide and protein chemistry (Part I). PD MS of nucleotides, carbohydrates, lipids, and pigments will be reviewed in Part II (see the following issue of this journal). The review covers the literature from 1982 to 1994.

Mass Spectrometry↗
PubMed2006

Induction of neutral endopeptidase (NEP) activity of SK-N-SH cells by natural compounds from green tea.

Deposition of amyloid beta-peptide as senile plaques in the brain is one of the neuropathological hallmarks of Alzheimer's disease, which is the most prevalent progressive neurodegenerative disease leading to dementia. Neutral endopeptidase is one of the major beta-amyloid-degrading enzymes in the brain. To examine the influence of different polyphenols and other natural products from green tea extract (from Camellia sinensis, Theaceae), we used the neuroblastoma cell line SK-N-SH and studied the changes in the specific cellular neutral endopeptidase activity after long-term treatment with these substances. We have shown that caffeine leads to an increase in specific cellular neutral endopeptidase activity more than theophylline, theobromine or theanine. We have also shown that the combination of epicatechin, epigallocatechin and epigallocatechingallate with caffeine, theobromine or theophylline induced cellular neutral endopeptidase activity. It is suggested that the enhancement of cellular neutral endopeptidase activity by green tea extract and its natural products might be correlated with an elevated level of intracellular cyclic adenosine monophosphate.

Cell Line, Tumor↗
PubMed2002

A review on usnic acid, an interesting natural compound.

Lichens are a world-widespread consortium of fungal and photosynthetic partners. Usnic acid is one of the most common and abundant lichen metabolites, well known as an antibiotic, but also endowed with several other interesting properties. This review summarises the most relevant studies on usnic acid, focusing on a number of biological activities in different fields. On the basis of the existing literature, usnic acid seems to be an exclusive lichen product. No synthetic derivatives more effective than the natural form are known. Both the (+) and (-) enantiomers of usnic acid are effective against a large variety of Gram-positive (G+) bacterial strains, including strains from clinical isolates, irrespective of their resistant phenotype. Of particular relevance is the inhibition of growth of multi-resistant strains of Streptococcus aureus, enterococci and mycobacteria. The (+)-usnic acid enantiomer appears to be selective against Streptococcus mutans without inducing perturbing side effects on the oral saprophyte flora. On the other hand, the (-)-usnic acid enantiomer is a selective natural herbicide because of its blocking action against a specific key plant enzyme. Other recognised characteristics of usnic acid are ultraviolet absorption and preserving properties. The toxicology, the in vitro anti-inflammatory effects and the mechanism of action of usnic acid need to be investigated in greater detail in order to reach clinical trials and to allow further applications. Furthermore, more research is needed to make possible intensive lichen culture, in order to produce large quantities of lichen substances for pharmaceutical, cosmetic and agricultural purposes. Some biological aspects, i.e. the possible biological roles of usnic acid, are discussed.

Anti-Bacterial Agents↗
PubMed2006

Natural compounds obtained through centrifugal molecular distillation.

Soybean oil deodorized distillate (SODD) is a byproduct from refining edible soybean oil; however, the deodorization process removes unsaponifiable materials, such as sterols and tocopherols. Tocopherols are highly added value materials. Molecular distillation has large potential to be used in order to concentrate tocopherols, because it uses very low levels of temperatures because of the high vacuum and short operating time for separation and, also, it does not use solvents. However, nowadays, the conventional way to recover tocopherols is carrying out chemical reactions prior to molecular distillation, making the process not so suitable to deal with natural products. The purpose of this work is to use only molecular distillation in order to recover tocopherols from SODD. Experiments were performed in the range of 140-220 degrees C. The feed flow rate varied from 5 to 15 g/min. The objective of this study was to remove the maximum amount of free fatty acids (FFA) and, so, to increase the tocopherol concentration without add any extra component to the system. The percentage of FFA in the distillate stream of the molecular still is larger at low feed flow rates and low evaporator temperatures, avoiding thermal decomposition effects.

Centrifugation↗
PubMed2005

11,11'-dideoxy-verticillin: a natural compound possessing growth factor receptor tyrosine kinase-inhibitory effect with anti-tumor activity.

11,11'-dideoxy-verticillin, a compound of the novel epidithiodioxopiprazine structural class, is isolated from the traditional Chinese medicinal herb Shiraia bambusicola. The present study demonstrated for the first time that 11,11'-dideoxy-verticillin has potent tyrosine kinase-inhibitory and anti-tumor activities. In the cell-free ELISA tyrosine kinase assay, 11,11'-dideoxy-verticillin significantly inhibited the activities of epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1 (VEGFR-1/Flt-1) and human epidermal growth factor receptor-2 (HER2/ErbB-2), with relative specificity on EGFR and VEGFR-1 with IC50s of 0.136+/-0.109 and 1.645+/-0.885 nM, respectively. Exposure of 11,11'-dideoxy-verticillin for 1 h to EGFR-overexpressed MDA-MB-468 human breast carcinoma cells and HER2-overexpressed SK-OV-3 human ovarian adenocarcinoma cells resulted in obvious inhibition of EGF-induced phosphorylation of EGFR and HER2. In addition, 11,11'-dideoxy-verticillin also inhibited the EGF-induced phosphorylation of Erk1/2, but had no effect on the phosphorylation of AKT in both tumor cell lines. Moreover, 11,11'-dideoxy-verticillin has potent anti-tumor activity. In vitro cytotoxicity assay showed that 11,11'-dideoxy-verticillin potently inhibited the proliferation of four human breast tumor cell lines with an average IC50 value of 0.2 microM. In vivo, 11,11'-dideoxy-verticillin exhibited remarkable efficacy against mice sarcoma 180 and hepatoma 22 after daily i.p. administration of 0.5 or 0.75 mg/kg with inhibition rates ranging from 45.0 to 72.4%. Treated with 11,11'-dideoxy-verticillin at 0.5-2.0 microM for 36 h, MB-MB-468 cells exhibited significant apoptotic morphological changes. At low concentrations (0.0625-0.5 microM) for 24 h, 11,11'-dideoxy-verticillin induced a dose-dependent accumulation of MDA-MB-468 cells in the G2/M phase of the cell cycle. These results indicate that 11,11'-dideoxy-verticillin is a naturally derived growth factor receptor tyrosine kinase inhibitor with potent anti-tumor activity.

Animals↗
PubMed2006

Biological activities of some natural compounds from Sideritis sipylea Boiss.

In this work, several diterpenes including siderol, linearol and epicandicandiol were isolated from Sideritis sipylea Boiss collected from Izmir-Karaburun-Akdag, Turkey. In addition, diacetate derivatives of linearol and epicandicandiol were obtained. The antimicrobial activites of all these compounds against the bacteria Staphylococcus aureus (ATTC 25923), Bacillus subtilis (ATCC 6633), Escherichia coli (ATCC 11230), Pseudomonas aeruginosa (ATCC 27853) and the fungus Candida albicans (ATCC 90028) were studied. Antimicrobal activity was measured by the well-diffusion method. Except for C. albicans all microorganisms were tested against antibiotic discs in comparison with the studied compounds.

Bacillus subtilis↗
PubMed2006

Natural compounds from Danshen suppress the activity of hepatic stellate cells.

Danshen is an herbal medication frequently used in oriental medicine to treat liver or kidney malfunction. In the course of our studies, we observed that compounds purified from Danshen exhibit an inhibitory activity against Discoidin Domain Receptor 2 (DDR2) tyrosine kinase. Through this inhibition, these compounds also inhibited the growth of HSC T6 cells and suppressed the expression of alpha-smooth muscle actin and MMP2, as well as collagen synthesis, all of which are increased in activated liver stellate cells. Given that activation of liver stellate cells is the hallmark of liver fibrosis and that DDR2 plays a critical role in this activation, these results suggest that one of the pharmacological activities of Danshen extract that protects the liver is the inhibition of key cell-signaling kinases, such as DDR2, in liver stellate cells.

Actins↗
PubMed2006

Extremolytes: Natural compounds from extremophiles for versatile applications.

Extremophilic microorganisms have adopted a variety of ingenious strategies for survival under high or low temperature, extreme pressure, and drastic salt concentrations. A novel application area for extremophiles is the use of "extremolytes," organic osmolytes from extremophilic microorganisms, to protect biological macromolecules and cells from damage by external stresses. In extremophiles, these low molecular weight compounds are accumulated in response to increased extracellular salt concentrations, but also as a response to other environmental changes, e.g., increased temperature. Extremolytes minimize the denaturation of biopolymers that usually occurs under conditions of water stress and are compatible with the intracellular machinery at high (>1 M) concentrations. The ectoines, as the first extremolytes that are produced in a large scale, have already found application as cell protectants in skin care and as protein-free stabilizers of proteins and cells in life sciences. In addition to ectoines, a range of extremolytes with heterogenous chemical structures like the polyol phosphates di-myoinositol-1,1'-phosphate, cyclic 2,3-diphosphoglycerate, and alpha-diglycerol phosphate and the mannose derivatives mannosylglycerate (firoin) and mannosylglyceramide (firoin-A) were characterized and were shown to have protective properties toward proteins and cells. A range of new applications, all based on the adaptation to stress conditions conferred by extremolytes, is in development.

Adaptation, Physiological↗
PubMed2003

Ritterazine B, a new cytotoxic natural compound, induces apoptosis in cancer cells.

PURPOSE: Ritterazine B, one of the ritterazine analogues extracted from Ritterella tokioka, has been shown to be chemically similar to cephalostatin 1, and among the ritterazine derivatives is the most cytotoxic to P388 murine leukemia cells. The objective of this study was to determine the cytotoxicity of ritterazine B to non-small-cell lung cancer (NSCLC) cells in vitro and its effects on the cell cycle and apoptosis. METHODS: The cytotoxicity of ritterazine B against PC14 NSCLC cells was investigated using a 4-day MTT assay. Morphological changes in cells after exposure to this compound were evaluated by phase-contrast microscopy. The effects on the cell cycle of HL-60 leukemia cells and PC14 cells were elucidated by flow cytometry and an in vitro CDK/cyclin kinase assay. Induction of apoptosis in HL-60 cells was assessed using the TUNEL assay and Hoechst 33342 staining. In addition, molecules involved in apoptosis were evaluated by Western blotting. RESULTS: Ritterazine B exerted strong cytotoxic effects against PC14 cells with a mean GI(50) of 75.1 n M. Cell cycle analysis showed that ritterazine B caused accumulation of HL-60 and PC14 cells at the G2/M checkpoint. Furthermore, ritterazine B-treated HL-60 cells became multinucleated, and at a concentration of 20 n M this resulted in the onset of apoptosis. Neither cleavage of caspase target molecules nor phosphorylation of bcl-2 were observed in ritterazine B-treated HL-60 cells. CONCLUSIONS: These results indicate that ritterazine B might be a potent inducer of apoptosis acting via a novel antimitotic mechanism.

Antineoplastic Agents↗
PubMed1992

alpha-Hydroperoxy diethyl peroxide, an unusual natural compound isolated from an ascidian (Phallusia mammillata): acute toxicity in DDY mice.

alpha-Hydroperoxy diethyl peroxide, a novel compound found in the tunic of ascidians, has two peroxide moieties per molecule. Since ascidians are a widely served food item in Japan, human exposure to this compound potentially exists in the seafood preparation industries. No toxicological data have so far been published on this compound, and so we determined the intraperitoneal 6-day LD50 in mice and conducted histopathological examinations. The 6-day LD50 was found to be 199 mg/kg with 95% confidence limits of 126-314 mg/kg. Histopathological examination revealed necrosis induced in a variety of cells that had been directly exposed to the compound. These cells included hepatocytes, parenchymal pancreatic cells and fat cells. It is concluded that direct contact with this compound is likely to elicit cellular necrosis of various organs. The specific toxicological effects are probably dependent on the route of exposure.

Animals↗
PubMed2005

Identification of natural compounds with antiviral activities against SARS-associated coronavirus.

More than 200 Chinese medicinal herb extracts were screened for antiviral activities against Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay for virus-induced cytopathic effect (CPE). Four of these extracts showed moderate to potent antiviral activities against SARS-CoV with 50% effective concentration (EC50) ranging from 2.4 +/- 0.2 to 88.2 +/- 7.7 microg/ml. Out of the four, Lycoris radiata was most potent. To identify the active component, L. radiata extract was subjected to further fractionation, purification, and CPE/MTS assays. This process led to the identification of a single substance lycorine as an anti-SARS-CoV component with an EC50 value of 15.7 +/- 1.2 nM. This compound has a CC50 value of 14980.0 +/- 912.0 nM in cytotoxicity assay and a selective index (SI) greater than 900. The results suggested that four herbal extracts and the compound lycorine are candidates for the development of new anti-SARS-CoV drugs in the treatment of SARS.

Amaryllidaceae Alkaloids↗