Bronwyn G. Hughes

Inhibition of whole blood platelet-aggregation by compounds in garlic clove extracts and commercial garlic products

The inhibitory effects of adenosine and 16 quantitatively determined organosulfur compounds derived from garlic cloves or commercial garlic preparations on collagen stimulated in vitro platelet aggregation in whole blood were determined. An estimation of the anti-aggregatory activity of several brands of the major types of commercial garlic preparations was determined from the activities of the individual compounds present in each sample. In platelet rich plasma (PRP) most of the anti-aggregatory activity of garlic clove homogenates was due to adenosine; however, in whole blood neither adenosine nor the polar fraction had any effect and all of the anti-aggregatory activity was due to allicin and other thiosulfinates. Allicin was equally active in whole blood and PRP. Among brands there was a several-fold variation in content of the organosulfur compounds and activity for all types of garlic products tested. The best garlic powder tablets were equally as active as clove homogenates whereas steam-distilled oils were 35% as active and oil-macerates (due to low content) only 12% as active. A garlic product aged many months in aqueous alcohol had no activity. For steam-distilled oils, most of the activity was due to diallyl trisulfide. For the oil-macerates, most of the activity was due largely to the vinyl dithiins. Ajoene, an exclusive component of the oil-macerates, had highest specific activity of all the compounds tested but, because of its low concentration, had only 13% of the activity of diallyl trisulfide and 3% of the activity of allicin. Compounds which may be active in vivo are discussed.

In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives

Anthraquinones and anthraquinone derivatives were characterized for their antiviral and virucidal activities against viruses representing several taxonomic groups. One of these compounds, hypericin, had activity against vesicular stomatitis virus, herpes simplex virus types 1 and 2, parainfluenza virus, and vaccinia virus (from 0.5 to 3.8 log10 reductions in infectivity) at concentrations of less than 1 microgram/ml as determined by a direct pre-infection incubation assay. Human rhinovirus was not sensitive to hypericin at concentrations up to 10 micrograms/ml. Addition of small amounts of Tween-80 to solutions containing hypericin enhanced, by up to 2.6 log10, hypericins virucidal activity. Anthraquinones and anthraquinone derivatives with the hydroxyl and alkyl substitution pattern of emodin (i.e. emodin, emodin anthrone, emodin bianthrone and hypericin) were active against the enveloped viruses tested. The following general pattern of activity was found: hypericin greater than emodin bianthrone greater than emodin anthrone greater than emodin. Chrysophanic acid, aloe-emodin, and sennosides A and B did not possess activity against any of the viruses tested.

Evaluation of the antiviral activity of anthraquinones, anthrones and anthraquinone derivatives against human cytomegalovirus

A number of anthraquinones, anthrones and anthraquinone derivatives were evaluated for antiviral activity against human cytomegalovirus (HCMV) as well as for cytotoxicity. Of those compounds evaluated, quinalizarin, emodin, rhein, hypericin, protohypericin, alizarin, emodin bianthrone and emodin anthrone showed antiviral activity against a normal laboratory HCMV strain, AD-169. When tested against a ganciclovir-resistant strain of HCMV, the EC50 values for quinalizarin, rhein and alizarin were superior to the values obtained for the AD-169 strain of HCMV. These results suggest that these compounds will be useful as prototypes for synthesizing a class of anti-HCMV drugs that are effective against ganciclovir-sensitive and -resistant strains of HCMV.

Cell cycle arrest and differential gene expression in HT-29 cells exposed to an aqueous garlic extract

Epidemiological data show an inverse correlation between garlic consumption and the risk for colon cancer. To examine this relationship, HT-29 human adenocarcinoma cells were cultured in the presence and absence of an aqueous garlic extract. Garlic treatment resulted in a fraction of cells detaching from the culture flasks. These cells remained viable. Flow cell cytometry showed that untreated cells exhibited a normal distribution among phases of the cell cycle, with 12% of cells at the G2/M boundary. Of the garlic-treated cells remaining attached to the flask, 27% were present at the G2/M boundary. Treated cells that detached from the flask were found almost exclusively (89%) at the G2/M boundary. RNA fingerprinting and microarray analysis showed that expression of the gene for menin was twice as high in control cells as in detached treated cells. In contrast, expression of genes for epidermal growth factor receptor and integrin-α6 was nearly twice as high in detached treated cells as in control cells. These changes in gene expression were consistent with an arrest of the cell cycle at the G2/M boundary. Garlic=s arrest of the cell cycle in human adenocarcinoma cells may explain in part its anticarcinogenic properties.