Journal of Medicinal Food

Policosanol is a cholesterol-lowering drug purified from sugar cane. Previous toxicological studies have not demonstrated any policosanol-related toxicity, even with long-term oral administration at 500 mg/kg, a dose 1,724 times larger than the maximal therapeutic dose (20 mg/day) recommended to date. The present study was undertaken to investigate the oral toxicity of policosanol administered for 6 months in doses up to 5,000 mg/kg to Sprague-Dawley rats. Animals were randomly distributed in five groups (15 animals per dose per sex): a control and four groups given oral policosanol (50, 500, 2,500, or 5,000 mg/kg). Eight treated rats (6 males, 2 females) died during the study, five of them (4 males, 1 female) from among those receiving the highest dose (5,000 mg/kg). According to necropsy, all deaths were related to gavage manipulation of higher doses. Although the differences were not significant, body weight gain and food consumption in the groups receiving 2,500 or 5,000 mg/kg tended to be lower than in the control group. Nevertheless, no drug-related toxicity symptoms were detected. Analysis of blood biochemistry, hematology, organ weight ratios, and histopathological findings did not show significant differences compared with controls, nor any tendency with the dose. Therefore, the present study did not show any new evidence of oral toxicity of policosanol, and the findings observed were a consequence of long-term administration by gastric gavage of the highly concentrated suspensions needed to reach the higher doses. It is concluded that policosanol chronically administered by the oral route is safe and that no drug-related toxicity was demonstrated.

Policosanol is a natural mixture of higher aliphatic primary alcohols isolated from sugar cane wax (Saccharum officinarum L.). It has cholesterol-lowering effects demonstrated in experimental models and in patients with type II hypercholesterolemia, with positive pleiotropic properties such as inhibition of platelet aggregation and lipid peroxidation. Policosanol reduced thromboxane A₂ and malondialdehyde (MDA) serum levels in animals and human beings. Because nitric oxide (NO) can be destroyed by oxygen-derived radicals and policosanol possesses an antioxidant effect, the purpose of this study was to determine the putative interaction between policosanol and nitroprusside (an NO-containing substance) on platelet aggregation and arterial blood pressure in rats. The percentage of inhibition of adenosine diphosphate–induced aggregation (preincubation with nitroprusside) was higher in platelet-rich plasma of policosanol-treated animals than in control animals. Pretreatment with single doses of policosanol significantly increased the nitroprusside-induced hypotensive effect.

D-002 is a mixture of higher aliphatic alcohols isolated from beeswax that inhibits rat microsomal lipid peroxidation in vitro and in vivo. This study was undertaken to investigate whether D-002 also inhibits lipid peroxidation in older subjects. The free radical theory of aging suggests that progressive defects in the protection against free radical reactions leads to progressive deleterious effects of free radicals on cells and tissues. This free radical damage has been implicated in several pathophysiological processes associated with the chronic degenerative diseases that occur with aging. Forty-eight older subjects were randomly assigned, in a double-blind fashion, to receive placebo or D-002 tablets (50 mg/day) once daily. At baseline, D-002 and placebo groups were well matched regarding several variables. D-002 significantly reduced the susceptibility of nonfractionated plasma samples to copper-mediated lipid peroxidation. It also significantly increased the length of the lag phase (P< .001) and the total antiioxidant status (P < .05) compared with baseline and placebo. In addition, D-002 significantly decreased malondialdehyde levels (expressed in terms of thiobarbituric acid reactive substances (TBARS, P < .001) compared with baseline, but not with placebo. No significant changes on lipid peroxidation parameters were observed in the placebo group. We conclude that D-002 treatment may be useful to prevent or manage certain pathophysiological conditions in the elderly.

D-002 is a natural mixture of higher aliphatic primary alcohols isolated from beeswax that has antioxidant and antiulcer properties. Because the role of lipid peroxidation in gastric damage is well recognized, this work was designed to investigate the possible effect of D-002 on lipid peroxidation in gastric mucosa in two experimental models of gastric injury in rats: (1) gastric ulcer induced by indomethacin and (2) mucosal injury induced by ischemia-reperfusion (I-R). The results demonstrated a remarkable protective effect of D-002 on lipid peroxidation in gastric ulcer induced by indomethacin and a moderate protective effect of D-002 on gastric erosions and lipid peroxidation induced by I-R.

D-003 is a mixture of very long chain aliphatic acids purified from sugar cane wax with cholesterol-lowering effects. The present study was undertaken to investigate the in vivo cytotoxic and genotoxic potential of D-003 using three established assays: bone marrow micronucleus, sperm morphology, and single cell gel electrophoresis (Comet) assay. In a first experimental series, CEN/NMRI mice (6–8 animals per sex per group) were administered D-003 by gastric gavage at 5, 50, or 500 mg/kg for 90 days, then sacrificed 24 hours after the last administration. The effects on bone marrow micronucleus were evaluated only in female mice. D-003 (5–500 mg/kg) did not increase the frequency of micronucleated polychromatic erythrocytes, nor the ratio of polychromatic to normochromatic erythrocytes, compared with the controls. The assessment of the effects on sperm morphology showed that D-003 did not change the sperm count or the frequency of all types of abnormal head shapes, compared with the controls. In a second series, the micronucleus assay was performed in mice of both sexes given 2,000 mg/kg for 6 days. Likewise, in this series, neither cytotoxic nor genotoxic effects were found. Finally, five male Sprague-Dawley rats were treated with D-003 (1,250 mg/kg) by oral gavage for 90 days, and Comet assay on liver cells was performed. No single-strand breaks or alkali-labile site induction on DNA was observed. These results indicate that D-003 does not show evidence of cytotoxic or genotoxic activity on either somatic or germ cells in rodents.

The recent and essential reports on the biological activity of the principal phytophenols of Vitis vinifera and wine, with special attention to resveratrol, are reviewed. The phytophenols are arbitrarily divisible into single-ring phenolic acids, bisphenols including stilbenes, tricyclic phenols (flavonoids) and their subclasses, and oligomeric and polymeric species, the proanthocyanidins and anthocyanidins. Their precursors and the stilbenes, including resveratrol with its analogs and conjugates, appear to be of preventative and possibly therapeutic value in atherosclerosis and certain neoplastic and inflammatory afflictions. The probable mechanisms are free radical scavenging and selective interference with a multitude of factors affecting the division cycle of rapidly and abnormally proliferating mammalian cells. Reviewed are studies of natural occurrence, extraction methods, bioavailability, analytical detection, and metabolism of resveratrol, as well as its effects on cancer and inflammation, atherosclerosis, and neurons. Because grape extracts are a convenient alimentary source of salutary phytochemicals to supplement currently prevalent occidental food and resveratrol appears to be especially useful, it could conveniently be added in biosignificant amounts to the grape extracts provided that their extraction, contents, and quality controls are instituted.

Ascorbic acid (AA) and its derivatives participate in vitro in oxidative-reductive reactions both as antioxidants and as prooxidants. The physiological relevance of these prooxidant effects of AA and its derivatives remains unclear. There is little evidence that AA can initiate formation of reactive oxygen species (ROS) or lipid peroxidation in cells or tissue. In order to examine the effect of AA and its derivative palmitoyl ascorbate on in situ intracellular ROS production and lipid peroxidation, 2^′,7^′-dichlorofluorescin diacetate (DCFH-DA) and cis-parinaric acid were used as fluorescent probes in cultural neonatal foreskin fibroblasts. The results demonstrated that the effect of AA depended on the in vitro growth conditions. AA induced augmentation of the intracellular ROS concentration in newly plated (24 hours) cells. However, in cells cultured for 72 hours, AA had a different effect: it moderately reduced intracellular ROS concentration but stimulated lipid peroxidation in the cytoplasmic membrane. Palmitoyl ascorbate demonstrated significant inhibition of intracellular DCFH-DA oxidation presumably caused by inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.

The quantitative distribution of flavan-3-ols was determined using high-performance liquid chromatography in several grape seed extracts (GSEs). In all GSEs, polymers of four or more carbon units were the group of procyanidins present in the highest concentration, the real quantity ranging between 60% and 99.5%. In a previous paper we established a relation between antioxidant and anticlastogenic activity of GSEs. A higher grade of polymerization in GSEs allows the existence of a higher number of conjugated structures and higher antioxidant activity. The radioprotective effects of GSEs with various grades of polymerization were determined by use of the micronucleus test for anticlastogenic activity, evaluating the reduction in the frequency of micronuclei in cytokinesis-blocked cells of human lymphocytes exposed to γ-rays. The radioprotective efficiency of GSEs was according to their grade of polymerization: GSE3 > GSE2 > GSE1 > dimethylsulfoxide. The higher antioxidant capacity and anticlastogenic activity of GSEs can be explained, structurally, by the high number of conjugated structures between the catechol groups in the B-rings and the 3-OH free groups of the polymeric polyphenolic skeleton and, in addition, by the stability of the aroxyl flavonoid radical generated in the processes.