The pharmacokinetics (PK) of hydroxytyrosol and its metabolites were characterized following oral administration to Sprague-Dawley rats of 3.85 and 7.70 g of destoned Arbequina table olives/kg. ...Plasma samples were analyzed using a fully validated method consisting of liquid extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Noncompartmental PK analysis of hydroxytyrosol demonstrated linear PK between doses of 2.95 and 5.85 mg hydroxytyrosol/kg. Half-life was approximately 2.5 h, while mean residence time was around 4 h. Clearance occurred by conversion to two sulfate and two glucuronide conjugates. The area under the plasma concentration–time curve (AUC) ratios of metabolites versus parent hydroxytyrosol was approximately 7–9-fold for the sulfate and below 0.25 for the glucuronide, indicating sulfation as the predominant metabolic pathway. Despite extensive metabolism, hydroxytyrosol remained in plasma for up to 8 h with AUCs of 4293 and 8919 min·nmol/L for the doses of 3.85 and 7.70 g/kg, respectively. Therefore, table olives provide a more sustained plasma profile than other foods containing hydroxytyrosol, which may enhance its health-protecting activities.
We have previously reported the anticarcinogenic effects of an olive fruit extract composed of pentacyclic triterpenes, the main components of which are maslinic acid (73·25 %) and oleanolic acid ...(25·75 %). Here we examined the effects of the individual components on proliferation, necrosis and apoptosis rates by fluorescence-based techniques in human HT-29 colon cancer cells. Oleanolic acid showed moderate antiproliferative activity, with an ec50 of 160·6 (se 10·6) μmol/l, and moderate cytotoxicity at high concentrations ( ≥ 250 μmol/l). On the other hand, maslinic acid inhibited cell growth with an ec50 of 101·2 (se 7·8) μmol/l, without necrotic effects. Oleanolic acid, which lacks a hydroxyl group at the carbon 2 position, failed to activate caspase-3 as a prime apoptosis protease. In contrast, maslinic acid increased caspase-3-like activity at 10, 25 and 50 μmol/l by 3-, 3·5- and 5-fold over control cells, respectively. The detection of ROS in the mitochondria, which serve as pro-apoptotic signal, evidenced the different bioactivity of the two triterpenes. Confocal microscopy analysis revealed that maslinic acid generated superoxide anions while oleanolic acid-treated cells did not differ from the control. Completion of apoptosis by maslinic acid was confirmed microscopically by the increase in plasma membrane permeability, and detection of DNA fragmentation. In conclusion, the anticancer activity observed for olive fruit extracts seems to originate from maslinic acid but not from oleanolic acid. Maslinic acid therefore is a promising new compound for the chemoprevention of colon cancers.
d-Fagomine is an iminosugar originally isolated from seeds of buckwheat (Fagopyrum sculentum Moench), present in the human diet and now available as a pure crystalline product. We tested d-fagomine ...for activities connected to a reduction in the risk of developing insulin resistance, becoming overweight and suffering from an excess of potentially pathogenic bacteria. The activities were: intestinal sucrase inhibition in vitro (rat mucosa and everted intestine sleeves), modulation of postprandial blood glucose in rats, bacterial agglutination and bacterial adhesion to pig intestinal mucosa. When ingested together with sucrose or starch, d-fagomine lowered blood glucose in a dose-dependent manner without stimulating insulin secretion. d-Fagomine reduced the area under the curve (0–120 min) by 20 % (P < 0·01) and shifted the time to maximum blood glucose concentration (Tmax) by 15 min at doses of 1–2 mg/kg body weight when administered together with 1 g sucrose/kg body weight. Moreover, d-fagomine (0·14 mm) agglutinated 60 % of Enterobacteriaceae (Escherichia coli, Salmonella enterica serovar Typhimurium) populations (P < 0·01), while it did not show this effect on Bifidobacterium spp. or Lactobacillus spp. At the same concentration, d-fagomine significantly (P < 0·001) inhibited the adhesion of Enterobacteriaceae (95–99 % cells in the supernatant) and promoted the adhesion of Lactobacillus acidophilus (56 % cells in the supernatant) to intestinal mucosa. d-Fagomine did not show any effect on bacterial cell viability. Based on all this evidence, d-fagomine may be used as a dietary ingredient or functional food component to reduce the health risks associated with an excessive intake of fast-digestible carbohydrates, or an excess of potentially pathogenic bacteria.
Arbequina table olive (AO) consumption lowers blood pressure (BP) in spontaneously hypertensive rats (SHR). This study evaluates whether dietary supplementation with AO induced changes in the gut ...microbiota that are consistent with the purported antihypertensive effects. Wistar-Kyoto rats (WKY-c) and SHR-c received water, while SHR-o were supplemented by gavage with AO (3.85 g kg
−1
) for 7 weeks. Faecal microbiota was analysed by 16S rRNA gene sequencing. SHR-c showed increased Firmicutes and decreased Bacteroidetes compared to WKY-c. AO supplementation in SHR-o decreased BP by approximately 19 mmHg, and reduced plasmatic concentrations of malondialdehyde and angiotensin II. Moreover, reshaped faecal microbiota associated with antihypertensive activity by lowering
Peptoniphilus
and increasing
Akkermansia
,
Sutterella
,
Allobaculum
,
Ruminococcus
, and
Oscillospira
. Also promoted the growth of probiotic strains of
Lactobacillus
and
Bifidobacterium
and modified the relationship of
Lactobacillus
with other microorganisms, from competitive to symbiotic. In SHR, AO promotes a microbiota profile compatible with the antihypertensive effects of this food.
The daily intake of table olives to spontaneously hypertensive rats induced changes in faecal microbiota associated with antihypertensive activity and promoted the growth of probiotic strains.
trans-Resveratrol was reported to have health benefits including anticarcinogenic effects and protection against cardiovascular disease. One of the mechanisms by which it exerts its action is through ...modulating the estrogen response systems. Because estrogen is involved in male reproductive biology, we investigated the effect of trans-resveratrol on testis and spermatogenesis. Adult male rats were divided into 2 groups. The treated group was administered by gavage 20 mg/(kg · d) of trans-resveratrol suspended in 10 g/L of carboxymethylcellulose for 90 d, whereas the control group received only carboxymethylcellulose during the same period. The relative weight of testes did not differ between the groups. However, the diameter of the seminiferous tubules was significantly reduced from 437.5 ± 0.1 microm in the controls to 310.9 ± 0.1 microm in the resveratrol-treated rats. This decrease was accompanied by a significant increase in tubular density, from 3.20 ± 0.18 in controls to 6.58 ± 0.18 tubules/mm² in the treated group. Moreover, sperm counts were significantly greater in the resveratrol-treated rats (24.8 ± 3.30 x 10⁷) than in the control group (14.1 ± 0.80 x 10⁷), but sperm quality did not differ. Serum concentrations of gonadotrophins and testosterone were significantly higher in the resveratrol-treated group. We identified a novel activity of trans-resveratrol. The daily oral administration of this phytochemical to adult male rats enhanced sperm production by stimulating the hypothalamic-pituitary-gonadal axis, without inducing adverse effects.
trans-Resveratrol is a polyphenol found in blueberries, grapes, and wine with cancer chemopreventive properties. The low bioavailability of this compound enhances its concentration in the luminal ...content and becomes a potential chemopreventive agent against colon cancer. In the present study, the antiproliferative and pro-apoptotic effects on the human colorectal carcinoma HT-29 cells as well as the mechanisms underlying these effects were examined. Proliferation, cytotoxicity, and apoptosis were measured by fluorescence-based techniques. Studies of dose-dependent effects of trans-resveratrol showed antiproliferative activity with an EC50 value of 78.9 ± 5.4 µM. Caspase-3 was activated in a dose-dependent manner after incubation for 24 h giving an EC50 value of 276.1 ± 1.7 µM. Apoptosis was also confirmed with microscopic observation of changes in membrane permeability and detection of DNA fragmentation. The activity of trans-resveratrol on the mitochondria apoptosis pathway was evidenced by the production of superoxide anions in the mitochondria of cells undergoing apoptosis. In conclusion, trans-resveratrol inhibits cell proliferation without cytotoxicity and induces apoptosis in HT-29. Results of the present study provide evidence demonstrating the antitumor effect of trans-resveratrol via a ROS-dependent apoptosis pathway in colorectal carcinoma.
Maslinic acid is a pentacyclic triterpene found in a variety of natural sources, ranging from herbal remedies used in traditional Asian medicine to edible vegetables and fruits present in the ...Mediterranean diet. In recent years, several studies have proved that maslinic acid exerts a wide range of biological activities, i.e. antitumor, antidiabetic, antioxidant, cardioprotective, neuroprotective, antiparasitic and growth-stimulating. Experimental models used for the assessment of maslinic acid effects include established cell lines, which have been often used to elucidate the underlying mechanisms of action, and also animal models of different disorders, which have confirmed the effects of the triterpene in vivo. Overall, and supported by the lack of adverse effects in mice, the results provide evidence of the potential of maslinic acid as a nutraceutical, not only for health promotion, but also as a therapeutic adjuvant in the treatment of several disorders.
The role attributed to polyphenols on human health needs to be correlated with their plasmatic concentrations after food consumption. Then, a method based on liquid–liquid extraction followed by ...highly sensitive LC-ESI-MS/MS analysis was developed to determinate 16 phenolic compounds in plasma. Validation gave appropriate recovery, matrix effect (80%–120%), linear correlation (R 2 > 0.995), precision (<15%), LOQ (0.04–2.51 nM), and short chromatographic run. The method was verified after the administration of Arbequina table olives to rats. A single dose of destoned olives was given by gavage, and plasmatic concentrations of polyphenols were analyzed at 30 min. Interestingly, the profile found in plasma greatly differed from that of the olives. Plasmatic concentrations, from highest to lowest, were salidroside, p-coumaric acid, hydroxytyrosol, verbascoside, tyrosol, luteolin, and luteolin-7-O-glucoside. In conclusion, a simple and robust method was developed, enabling the identification and quantification of unaltered polyphenols in plasma after olives consumption, thus demonstrating its suitability for pharmacokinetics studies.
trans-Resveratrol (trans-3,4′,5-trihydroxystilbene) is a natural phytoalexin present in grapes, red wine, berries and peanuts with health protecting properties. The low oral bioavailability indicated ...for this polyphenol, with the intestine as a bottleneck to its absorption, has promoted the large intestine as a potential target site for its chemopreventive activity. This review recapitulates the current evidence of the effects of trans-resveratrol on colon cancer. First, we describe the studies conducted in vitro which show that the protective activity takes place by inhibition of proliferation and induction of apoptosis. Secondly, the chemopreventive activity in animal models of colon carcinogenesis is revised. trans-Resveratrol not only reduces the number of preneoplastic lesions but also the incidence and multiplicity of tumors. Lastly, the article also reviews the available data on clinical trials. Altogether, the present findings support the hypothesis that the oral administration of trans-resveratrol might contribute to the prevention of colon carcinogenesis.
PDF
