Pharmacokinetics, bioavailability, metabolism and excretion of δ-viniferin in rats

A highly rapid and sensitive liquid chromatographic-electrospray ionization tandem mass spectrometric (LC-ESI-MS/MS) method was developed and validated for the determination of trans-δ-viniferin (Rs-1) in rat plasma, urine and feces. All biological samples were prepared by liquid-liquid extraction and hesperetin was included as an internal standard (IS). Chromatographic separation was achieved on a shim-pack XR-ODS column using a gradient mobile phase. MS/MS detection was performed by negative ion electrospray ionization. The method was sensitive with a lower limit of quantification of 1.42 ng/mL and linear over the range of 1.42-2172 ng/mL in all matrices. The method was applied to study the pharmacokinetics, bioavailability, metabolism, and excretion of Rs-1 in rats following a single oral or intravenous dose. Two metabolites, Rs-1 glucuronide and Rs-1 sulfate, were detected in plasma and in urine after administration of Rs-1. The absolute oral bioavailability of Rs-1 was 2.3%, and the total absorption rose to 31.5% with addition of its glucuronide and sulfate metabolites. Only 0.09% of the gavaged dose, including Rs-1 and metabolites, was excreted in the urine, while 60.3% was found in the feces in unchanged form. The results indicate that both poor absorption and extensive metabolism were the important factors that led to the poor bioavailability of Rs-1, which can provide a basis for further studies on structural modification and dosage form design.

Chemopreventive effect of alpha-viniferin in azoxymethane-induced mouse colorectal tumor and Caco-2 cells / 동물의과학연구지

alpha-Viniferin (AVF), a trimer of resveratrol, is known to have an anti-inflammatory effect via inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). It has been reported that up-regulated COX-2 and iNOS are expressed in colon cancer tissues of humans and rodents as well as pre-neoplastic aberrant crypt foci (ACF) of rodents. In this study, chemopreventive effects of AVF were assessed in Caco-2 cells as well as azoxymethane (AOM)-induced colorectal tumorigenesis in mice. Anti-tumor effect of AVF with regards to apoptotic induction was assessed by TUNEL and caspase-3 expression in human colon cancer Caco-2 cells. For development of ACF, AOM was administered with to mice intraperitoneally at a dose of 10 mg/kg once a week for 3 weeks. To induce colitis-related colon cancer, mice were administered a single dose of AOM (10 mg/kg) and 2% dextran sodium sulfate in drinking water. Mice treated with 0.05 and/or 0.1 mg of AVF by gavage showed significantly reduced development of ACF and colorectal tumors. Immunofluorescence detection in Caco-2 cells showed reduced COX-2 and iNOS expression, whereas cleavage of caspase-3 and apoptotic cell numbers increased upon AVF treatment. Immunostaining showed reduced expression levels of COX-2 and iNOS expression along with increased cleaved caspase-3 expression increased upon AVF treatment. These results suggest that AVF has chemopreventive effects on colorectal cancer via anti-inflammatory potential and pro-apoptotic activity.

Influence of different pretreatment methods on stilbenoids in grapevine / 中草药

Objective: To study the influence of different pretreatment methods of grapevine on the content of stibenoids in grapevine. Methods: The concentration of resveratrol and ε-viniferin was determined by HPLC, the fresh grapevine sample after picked was pretreated by different methods such as drying in the shade, drying in a dryer under different temperature, keeping in cold storage, slicing, pulverization, or whole treating, and the dynamic changes of stilbenoids in grapevine was investigated. Results: The contents of resveratrol and ε-viniferin in the fresh sample were very low, but the contents of resveratrol and ε-viniferin in the grapevine after picked would change significantly if treated as drying in the shade with whole branch, especially the content of resveratrol would rise from 0.063 mg/g to 7.175 mg/g with the extension of treating time, and the content of ε-viniferin would rise from 0.838 mg/g to 4.225 mg/g, but at some extent, the content would decline. The contents of resveratrol and ε-viniferin would not rise if the sample was pretreated as drying in the shade after slicing, drying in a dryer or keeping in cold storage. Conclusion: The influence of different pretreatment methods to the contents of resveratrol and ε-viniferin is very large, during drying process in the shade with whole branch, the contents of resveratrol and ε-viniferin change obviously and display the tendency of increasing at the earlier phase of the drying process, and then decrease with the extension of time. The contents of resveratrol and ε-viniferin can reach the level of utilization with the pretreatment of drying process in the shade.

Advances in pharmacological activities of viniferin / 中国药理学与毒理学杂志

Viniferin is the generic term of oligomers of resveratrol, which acts as phytoalexin in Leguminosae, Polygonaceae, Vitaceae, Ranunculaceae, Dipterocarpaceae and other plants. Viniferin plays important physiological roles in protecting against UV damage and resisting bacterial fungal and viral infection in plants. Nevertheless, these oligomers have shown various pharmacological activities including antioxidative activities, anti-pathogenic, anti-inflammatory and anti-tumor activities. This paper review the recent advances in research of viniferins microbes to show their key pharmaceutical activities for pharmaceutic references.