Cannabis sativa Extract Induces Apoptosis in Human Pancreatic 3D Cancer Models: Importance of Major Antioxidant Molecules Present Therein.

In recent years, interest in Cannabis sativa L. has been rising, as legislation is moving in the right direction. This plant has been known and used for thousands of years for its many active ingredients that lead to various therapeutic effects (pain management, anti-inflammatory, antioxidant, etc.). In this report, our objective was to optimize a method for the extraction of cannabinoids from a clone of Cannabis sativa L. #138 resulting from an agronomic test (LaFleur, Angers, FR). Thus, we wished to identify compounds with anticancer activity on human pancreatic tumor cell lines. Three static maceration procedures, with different extraction parameters, were compared based on their median inhibitory concentration (IC50) values and cannabinoid extraction yield. As CBD emerged as the molecule responsible for inducing apoptosis in the human pancreatic cancer cell line, a CBD-rich cannabis strain remains attractive for therapeutic applications. Additionally, while gemcitabine, a gold standard drug in the treatment of pancreatic cancer, only triggers cell cycle arrest in G0/G1, CBD also activates the cell signaling cascade to lead to programmed cell death. Our results emphasize the potential of natural products issued from medicinal hemp for pancreatic cancer therapy, as they lead to an accumulation of intracellular superoxide ions, affect the mitochondrial membrane potential, induce G1 cell cycle arrest, and ultimately drive the pancreatic cancer cell to lethal apoptosis.

Effects of increasing alfalfa (Medicago sativa) leaf levels on the fattening and slaughtering performance of organic broilers.

A feeding trial was conducted to evaluate the effects of increasing alfalfa leaf levels on the performance of organic broilers. The impact of drying temperature on the nutritional value of alfalfa leaves and thereby on broiler performance was studied using alfalfa leaves dried at either low (alfalfa leaves low temperature (ALLT)) or high temperatures (alfalfa leaves (AL)). Six hundred male Hubbard JA-757 broilers were divided into five feeding groups (Control (C), AL2, AL3, AL4 and ALLT5). Alfalfa leaf content was increased in each of the three fattening phases by 5% (C: 0%-0%-0%; AL2: 0%-5%-10%; AL3: 5%-10%-15%; AL4: 10%-15%-20%; and ALLT5: 10%-15%-20%). At the end of the experiment, broilers in group C had the highest body and carcass weights. Groups AL3, AL4 and ALLT5 showed the lowest body and carcass weights. In particular, the early introduction of alfalfa leaves (5% in phase 1) and high alfalfa leaf content (15%-20%) significantly decreased performance. Antinutritional substances such as saponins occur in alfalfa. In fact, the saponin analysis showed high contents of 3-Glc-Glc-28-Ara-Rha-medicagenic acid and HexA-dHex-Pen-Pen-Pen-zanhic acid in both high- and low-temperature alfalfa leaves.

Effects of processing steps on the phenolic content and antioxidant activity of beer.

A new analytical method (liquid chromatography-antioxidant, LC-AOx) was used that is intended to separate beer polyphenols and to determine the potential antioxidant activity of these constituents after they were allowed to react online with a buffered solution of the radical cation 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(•+)). Using the LC-AOx method, it was possible to demonstrate that the extent of the antioxidant activity was very much dependent on the phenolic compound considered. The method was also applied to the analysis of beer extracts and allowed the evaluation of their antioxidant activity at different steps of beer processing: brewing, boiling, and fermentation. This study showed that the total antioxidant activity remained unchanged throughout beer processing, as opposed to the polyphenolic content, which showed a 3-fold increase. Hopping and fermentation steps were the main causes of this increase. However, the increase measured after fermentation was attributed to a better extraction of polyphenols due to the presence of ethanol, rather than to a real increase in their content. Moreover, this method allowed the detection of three unknown antioxidant compounds, which accounted for 64 ± 4% of the total antioxidant activity of beer and were individually more efficient than caffeic acid and epicatechin.

Predicting the substrate specificity of a glycosyltransferase implicated in the production of phenolic volatiles in tomato fruit.

The volatile compounds that constitute the fruit aroma of ripe tomato (Solanum lycopersicum) are often sequestered in glycosylated form. A homology-based screen was used to identify the gene SlUGT5, which is a member of UDP-glycosyltransferase 72 family and shows specificity towards a range of substrates, including flavonoid, flavanols, hydroquinone, xenobiotics and chlorinated pollutants. SlUGT5 was shown to be expressed primarily in ripening fruit and flowers, and mapped to chromosome I in a region containing a QTL that affected the content of guaiacol and eugenol in tomato crosses. Recombinant SlUGT5 protein demonstrated significant activity towards guaiacol and eugenol, as well as benzyl alcohol and methyl salicylate; however, the highest in vitro activity and affinity was shown for hydroquinone and salicyl alcohol. NMR analysis identified isosalicin as the only product of salicyl alcohol glycosylation. Protein modelling and substrate docking analysis were used to assess the basis for the substrate specificity of SlUGT5. The analysis correctly predicted the interactions with SlUGT5 substrates, and also indicated that increased hydrogen bonding, due to the presence of a second hydrophilic group in methyl salicylate, guaiacol and hydroquinone, appeared to more favourably anchor these acceptors within the glycosylation site, leading to increased stability, higher activities and higher substrate affinities.