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Proanthocyanidins, from Ribes nigrum leaves, reduce endothelial adhesion molecules ICAM-1 and VCAM-1.

BACKGROUND: The effects of proanthocyanidins (PACs), isolated from blackcurrant (Ribes nigrum L.) leaves, on neutrophil accumulation during inflammatory processes were investigated in vivo and in vitro. METHODS: In vivo studies were performed using carrageenin-induced pleurisy in rats pre-treated with PACs. Exudate volume and PMNs accumulation were measured. Leukocyte cell adhesion molecules (LFA-1, Mac-1 and VLA-4) mobilization in circulating granulocytes were analysed by flow cytometry and endothelial cell adhesion molecules (ICAM-1 and VCAM-1) were detected by immunohistochemistry on lung sections. In vitro studies were conducted on endothelial LT2 cells, stimulated with TNF-alpha, to evaluate ICAM-1, IL-8 and VEGF mRNA expression upon PACs treatment. Data sets were examined by one-way analysis of variance (ANOVA) followed by a Scheffe post-hoc test. RESULTS: Pretreatment of the animals with PACs (10, 30 and 60 mg/kg) inhibited dose-dependently carrageenin-induced pleurisy in rats by reducing pleural exudate formation and PMNs infliltration. Leukocyte cell adhesion molecules mobilization was not down-regulated on granulocytes by PACs. Immunohistochemistry on lung sections showed a decreased production of endothelial cell adhesion molecules. In vitro experiments demonstrated that PACs were able to significantly inhibit ICAM-1 but not IL-8 and VEGF165 mRNA expression. Moreover, VEGF121 mRNA expression was dose-dependently enhanced. CONCLUSION: This study provides evidence to support the anti-inflammatory activity of proanthocyanidins is related to an inhibition of leukocyte infiltration which can be explained at least in part by a down-regulation of endothelial adhesion molecules, ICAM-1 and VCAM-1 and that these compounds are capable of modulating TNF-alpha-induced VEGF transcription.

Journal Article↗

ODR1, the key seed dormancy and germination regulator, promotes seed Proanthocyanidin biosynthesis via interaction with TTG1 and modulation of MBW complex activity.

Seed dormancy and germination are crucial for both plant survival and reproduction and for crop sowing and harvesting. Proanthocyanidins (PAs), one of the most abundant seed metabolites, play a role in enhancing dormancy and inhibiting germination. Multiple regulatory factors involved in PAs biosynthesis can alter seed dormancy or germination capacity. However, whether the dormancy or germination factors reciprocally influence the PAs biosynthesis is unclear. Here, we report that ODR1, a seed dormancy and germination key factor and a transcriptional (co-) repressor, can regulate seed PAs biosynthesis and act as a transcriptional co-activator. The odr1 mutant shows lighter seed coat color, decreased PAs contents, and reduced expression of PAs biosynthesis genes, which are restored in the ODR1 complementary lines. ODR1 interacts with TTG1 and forms a complex with TTG1/TT2/TT8 (three MBW complex components), enhancing their activation on promoters of PAs biosynthesis genes like DFR and ANS. Overexpressing TTG1 in the odr1-2 mutant rescues or even reverses PA-related phenotypes of odr1-2, confirming that ODR1-mediated regulation of PAs biosynthesis is dependent on TTG1. Moreover, three homologous copies of ODR1 in rapeseed were identified, and simultaneous knockout of them reduces the PAs contents. These results revealed the previously uncharacterized functions of ODR1 in PAs biosynthesis, suggested its conservation between Arabidopsis and rapeseed, and provided important gene resources for rapeseed variety improvement.

Proanthocyanidins↗

Proanthocyanidin: a natural crosslinking reagent for stabilizing collagen matrices.

While attempting to find a suitable crosslinking reagent for biopolymers, a naturally occurring proanthocyanidin (PA) obtained from grape seeds was selected to fix biological tissues. The cytotoxicity and crosslinking rate, reflected by the in vitro and in vivo degradation of fixed matrices has been studied. The shrinkage temperature of the fixed bovine pericardium increased from 66 to 86 degrees C. A cytotoxicity assay using fibroblast cultures revealed that PA is approximately 120 times less toxic than glutaraldehyde (GA), a currently used tissue stabilizer. In vitro degradation studies showed that fixed tissue was resistant to digestion by bacterial collagenase. Crosslinks between PA and tissues can be stabilized by decreasing the dielectric constant of the solution during storage. After subcutaneous implantation for periods ranging between 3 and 6 weeks, we found no apparent degradation of the GA- or PA-fixed tissues, whereas fresh tissue controls rapidly disintegrated. Beyond 6 weeks PA crosslinks began to degrade. More fibroblasts migrated and proliferated inside the PA-fixed implants compared with GA counterparts. Tissues crosslinked with PA manifested an enhanced collagen expression and deposition and did not calcify after implantation. GA, on the other hand, even after thorough rinsing continued to be cytotoxic, inhibited collagen synthesis and encouraged dystrophic calcification. Collagen matrices crosslinked with PA are expected to be of value in the design of matrices that will encourage cell ingrowth and proliferation, which are temporary in nature, and that are intended to regenerate or replace missing tissues, which can delay the biogradation of collagen. As such they should be of significant value in the emerging field of tissue engineering.

3T3 Cells↗

Chitosan/gelatin-based films crosslinked by proanthocyanidin.

Novel polymer networks consisting of crosslinked gelatin/chitosan were prepared by a solution casting technique. Methods for bulk crosslinking were developed to modify the gelatin/chitosan blends with the use of a nontoxic crosslinking reagent, proanthocyanidin (PA). FTIR spectral analyses of the preparations showed network formations of crosslinked gelatin, chitosan, and PA by amide and ester linkages. The crosslinked networks were stable in the aqueous state, and had improved mechanical properties and thermal stability when compared with nonlinked gelatin (G) and chitosan/gelatin (C/G) films. In vitro protease digestion and cell-culture studies showed that the PA-crosslinked C/G films are nontoxic and exhibited decreased biodegradation rate and a better ability to support cell adhesion and proliferation than noncrosslinked gelatin or chitosan alone. These results suggest that such a nontoxic crosslinked gelatin/chitosan scaffold can become a promising matrix for tissue-engineering applications.

Animals↗

Proanthocyanidins of mountain birch leaves: quantification and properties.

Proanthocyanidins (PAs; condensed tannins) are present in mountain birch leaves in soluble and cell wall-bound forms. Crude preparations of soluble PAs were isolated from birch leaves and purified by chromatography on a Sephadex LH-20 column with a yield of about 7% of leaf dry mass. Some chemical characteristics were elucidated with 13C-NMR and HPLC-ECI-MS. Birch leaf PAs were mainly delphinidin type oligo- and polymers with average molecular mass of about 3000. In order to quantify PAs, the method involving heating PA-containing materials in 1-butanol:hydrochloric acid (95:5, v/v), and spectrophotometric determination of the anthocyanidin monomers so formed was modified and optimised. Mature leaves were characterised by a relatively high content of PAs: mean values for soluble and bound PAs were 103 and 40 mg/g dry mass, respectively. In mature leaves the soluble PAs determined the total protein precipitation capacity (PPC) of extracts. In young leaves, the contribution of PAs to the total content of phenolics and the total PPC of tannins was about 20-25% only.

Anthocyanins↗

Reactive radical scavenging and xanthine oxidase inhibition of proanthocyanidins from Carallia brachiata.

Antioxidant-guided separation of Carallia brachiata bark led to a new A-type trimeric proanthocyanidin named carallidin (1), along with mahuannin A (2) and p-hydroxy benzoic acid (3). The structure of 1 was fully characterized by interpretation of spectroscopic data and chemical means. Compounds 1 and 2 exhibited radical scavenging against DPPH (IC(50) 102 and 182 microm) and superoxide radical (IC(50) 1.47 and 9.74 microm). In addition, 1 and 2 also inhibited xanthine oxidase with IC(50) values of 12.9 and 16.0 microm.

Free Radical Scavengers↗

Determination of proanthocyanidins in fresh grapes and grape products using liquid chromatography with mass spectrometric detection.

Fresh grapes and grape products, such as grape wine and grape juice, were analyzed for proanthocyanidins (PACs) using liquid chromatography with electrospray ionization mass spectrometric (MS) detection. PACs were successfully separated and analyzed on the basis of their protonated molecules, allowing the identification of PACs in different degrees of polymerization from monomers to oligomers (up to 7 units), and in various isomeric forms. Using reversed-phase high-performance liquid chromatography (HPLC) combined with MS detection, the PAC monomers, (+)-catechin (C), (-)-epicatechin (EC), (-)-catechin gallate (CG), and (-)-epicatechin gallate (ECG), were successfully quantified using selected ion monitoring (SIM) mode. Standard curves were fitted for each PAC ranging from 43.8 to 5600 ng/mL for C, from 42.2 to 5400 ng/mL for EC, from 36.7 to 4700 ng/mL for CG, and from 39.8 to 5100 ng/mL for ECG. Good linearity (r2>0.999) was achieved for each analyte. The accuracy and precision (RSD) were within 10% (n=8) at the limit of detection. This method allows direct quantification of monomeric PACs in fresh grapes and grape-derived products. Additionally, flow injection analysis (FIA) was applied to estimate the concentration levels of PAC oligomers by comparing their FIA-MS peak areas, which were well correlated (r2=0.936) to the total concentrations of PAC monomers.

Chromatography, Liquid↗

Characterization of proanthocyanidins in grape seeds using electrospray mass spectrometry.

Two proanthocyanidin (PA) fractions, one (Sdp3) with the mean degree of polymerization (mDP) of 3 and the other (Sdp9) with mDP of 9, were obtained from a Vitis vinifera cv. Shiraz grape seed extract. The PA fractions were directly analyzed by electrospray ionization mass spectrometry (ES-MS) and negative ion mass spectra were recorded. The mass spectrum of Sdp3 exhibited only singly charged ions corresponding to the molecular mass of PA with a degree of polymerization (DP) up to 9 (nonamers). In contrast, Sdp9 yielded rather complex mass spectra featuring ions with single [M - H](-), double [M - 2H](2-) and triple [M - 3H](3-) charge representing the molecular masses of PAs up to a DP of 28. In addition, the degree of galloylation per procyanidin (DG) was observed to be up to 5 (pentagallates) in Sdp3 and 8 (octagallates) in the Sdp9. This is the first evidence obtained by mass spectrometry for the distribution of grape seed PAs with such a high degree of polymerization and a broad diversity of galloylation. ES-MS data together with the complementary information provided by acid hydrolysis provides a detailed picture of the composition of grape seed PAs.

Anthocyanins↗

A novel proanthocyanidin IH636 grape seed extract increases in vivo Bcl-XL expression and prevents acetaminophen-induced programmed and unprogrammed cell death in mouse liver.

Several molecular events in the apoptotic or necrotic death of hepatocytes induced by acetaminophen (AAP) now appear to be well defined. Recent studies also indicate that select expression of bcl-Xl is possibly modified during AAP-induced liver injury. The purpose of this study was several-fold: (i) to examine the hepatoprotective ability of short-term (3-day) and long-term (7-day) exposures of a grape seed proanthocyanidin extract (GSPE) on AAP-induced liver injury and animal lethality; (ii) to monitor effects of GSPE on one of the prime targets of AAP, i.e., hepatocellular genomic DNA and associated apoptotic and necrotic death; and (iii) to unravel changes in the pattern of expression of an antiapoptotic gene, bcl-Xl in the liver. In order to investigate these events, male ICR mice (30-40 g) were administered nontoxic doses of GSPE (3 or 7 days, 100 mg/kg, po), followed by hepatotoxic doses of AAP (400 and 500 mg/kg, ip), and sacrificed 24 h later. Serum was analyzed for alanine aminotransferase activity (ALT) and the liver for histopathological diagnosis of apoptosis/necrosis. The ability of AAP to promote apoptotic DNA fragmentation and its counteraction by GSPE in the liver was also evaluated quantitatively (by a sedimentation assay) and qualitatively (by agarose gel electrophoresis). Portions of livers were also subjected to Western blot analysis (27,000g fraction of liver homogenates) to examine the pattern of expression of cell death inhibitory gene bcl-Xl. Results indicate that 7-day GSPE preexposure induced dramatic protection and markedly decreased liver injury and animal lethality culminated by AAP, when compared to a short-term 3-day exposure. Abrogation of toxicity was also mirrored in DNA fragmentation. Histopathological evaluation of liver sections showed remarkable counteraction of AAP-toxicity by this novel GSPE and substantial inhibition of both apoptotic and necrotic liver cell death. Agarose gel electrophoresis revealed that 7-day GSPE preexposure prior to AAP administration completely blocked Ca(2+)/Mg(2+)-Ca(2+)/Mg(2+)-dependent-endonuclease-mediated ladder-like fragmentation of genomic DNA and significantly altered the bcl-Xl expression. The most dramatic changes observed in this study were: (i) substantial increase in the expression of bcl-Xl in the liver by 7-day GSPE exposure alone; (ii) significant modification bcl-Xl expression by AAP alone; and (iii) dramatic inhibition of AAP-induced modification of bcl-Xl (phosphorylation?) expression by GSPE. In summary, these observations demonstrate that GSPE preexposure may significantly attenuate AAP-induced hepatic DNA damage, apoptotic and necrotic cell death of liver cells, and, most remarkably, antagonize the influence of AAP-induced changes in bcl-Xl expression in vivo.

Acetaminophen↗

Cytotoxicity induced by grape seed proanthocyanidins: role of nitric oxide.

Grape seed proanthocyanidin extract (GPSE) at high doses has been shown to exhibit cytotoxicity that is associated with increased apoptotic cell death. Nitric oxide (NO), being a regulator of apoptosis, can be increased in production by the administration of GSPE. In a chick cardiomyocyte study, we demonstrated that high-dose (500 microg/ml) GSPE produces a significantly high level of NO that contributes to increased apoptotic cell death detected by propidium iodide and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. It is also associated with the depletion of intracellular glutathione (GSH), probably due to increased consumption by NO with the formation of S-nitrosoglutathione. Co-treatment with L-NAME, a NO synthase inhibitor, results in reduction of NO and apoptotic cell death. The decline in reduced GSH/oxidized GSH (GSSG) ratio is also reversed. N-Acetylcysteine, a thiol compound that reacts directly with NO, can reduce the increased NO generation and reverse the decreased GSH/GSSG ratio, thereby attenuating the cytotoxicity induced by high-dose GSPE. Taken together, these results suggest that endogenous NO synthase (NOS) activation and excessive NO production play a key role in the pathogenesis of high-dose GSPE-induced cytotoxicity.

Acetylcysteine↗

Effects of elevated carbon dioxide and ozone on foliar proanthocyanidins in Betula platyphylla, Betula ermanii, and Fagus crenata seedlings.

Proanthocyanidins (PAs) or condensed tannins are a major group of phenolic compounds in the leaves of birch trees and many other woody and herbaceous plants. These compounds constitute a significant allocation of carbon in leaves and are involved in plant responses to environmental stress factors, such as pathogens or herbivores. In some plants, PA concentrations are affected by atmospheric carbon dioxide (CO(2)) and ozone (O(3)) levels that may influence, for example, species fitness, community structure, or ecosystem nutrient cycling. Therefore, a study on the quantitative response of PAs to elevated concentrations of carbon dioxide (CO(2)) and ozone (O(3)) was undertaken in seedlings of Betula platyphylla, Betula ermanii, and Fagus crenata. Seedlings were exposed to ambient or elevated O(3) and CO(2) levels during two growing seasons in the Kanto district in Japan. Ten open-top chambers were used for five different treatments with two replicates: filtered air (FA), ambient air (ambient O(3), 43 ppb; ambient CO(2), 377 ppm), elevated O(3) (1.5 x ambient O(3), 66 ppb), elevated CO(2) (1.5 x ambient CO(2), 544 ppm), and elevated O(3) and CO(2) combined. In addition, seedlings growing in natural conditions outside of chambers were studied. Leaf samples were analyzed for total PA concentrations by butanol-HCl assay and for polymeric PA concentrations by normal-phase high-performance liquid chromatography. Total PA concentrations in leaves of all species were similarly affected by different treatments. They were significantly higher in seedlings treated with elevated CO(2) and O(3) combined, and in seedlings growing outside chambers compared with the FA controls. F. crenata contained only traces of polymeric PAs, but significant species x treatment interaction was observed in the polymeric PA concentrations in B. ermanii and B. platyphylla. In B. platyphylla, leaves treated with elevated CO(2) + O(3) differed significantly from all other treatments. It was suggested that the strongest effect of elevated CO(2) and O(3) combined on leaf PA contents resulted from the additive effect of these environmental factors on phenolic biosynthesis.

Adaptation, Biological↗

Variation of proanthocyanidins in Lotus species.

The proanthocyanidin (PA) chemistry of 12 Lotus species of previously unknown PA content was examined in comparison with agricultural cultivars of L. pedunculatus, L. corniculatus, and L. tenuis and a "creeping" selection of L. corniculatus. Herbage harvested in winter 2000 and again in spring had extractable PA concentrations, estimations of which varied between 0.2 and 10.9% of dry matter. The four novel Lotus spp. with the highest concentrations were selected for further evaluation together with the agricultural accessions. PA concentrations in herbage were estimated for individual plants harvested in spring 2001 and bulk samples harvested in summer 2002-2003. PA oligomer and polymer fractions were separated by Sephadex LH-20 chromatography from aqueous acetone PA extracts of herbage. The chemical characteristics of the fractions were examined by acid catalyzed degradation with benzyl mercaptan, (13)C nuclear magnetic resonance spectroscopy, electrospray ionization (ESI), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). A wide variation was found in the chemical composition, mean degree of polymerization (mDP), and polydispersity of PAs from Lotus spp. Fractions from L. americanus, L. corniculatus "creeping selection," and L. pedunculatus consisted predominantly of prodelphinidin (PD) units, whereas PA from L. angustissimus and L. corniculatus consisted predominantly of procyanidin (PC) units. An approximately equal composition in terms of PC and PD units was found in L. parviflorus and L. suaveolens. In L. angustissimus, epicatechin is dominant in both extender and terminal units. In all Lotus PA fractions, the 2,3-cis isomers (epicatechin or epigallocatechin) predominated. Only trace amounts of PA were extracted from L. tenuis. The mDP of the PA fractions ranged from 8 to 97, with high mDP found only for L. pedunculatus and L. americanus. In the ESI-MS and MALDI-TOF-MS of the L. angustissimus PA fraction, ions for homo-PC oligomers were dominant, whereas ions for hetero-oligomers predominated in the other Lotus spp. Ions indicative of A-type linkages were observed in the MS of L. americanus. The results are discussed in terms of possible relationships between the concentration and composition of the PAs of Lotus spp. and ecological factors.

Ecology↗

Molecular cloning of Brassica napus TRANSPARENT TESTA 2 gene family encoding potential MYB regulatory proteins of proanthocyanidin biosynthesis.

Three members of Brassica napus TRANSPARENT TESTA 2 (BnTT2) gene family encoding potential R2R3-MYB regulatory proteins of proanthocyanidin biosynthesis were isolated. BnTT2-1, BnTT2-2, and BnTT2-3 are 1102 bp with two introns, and have a 938-bp full-length cDNA with a 260 amino acid open reading frame. They share 98.2-99.3% nucleotide and 96.5-98.5% amino acid identities to each other, and are orthologous to Arabidopsis thaliana TT2 (AtTT2) with 74.1-74.8% nucleotide and 71.1-71.8% amino acid identities. An mRNA type of BnTT2-2 was found to contain unspliced intron 2 and encode a premature protein. They all have an alternative polyadenylation site. BnTT2-1 and BnTT2-3 also have an alternative transcription initiation site. Aligned with AtTT2, their 5' untranslated regions (UTRs) are astonishingly conserved, and two conserved regions were also found in their 3' UTRs. Oligonucleotide deletion leads to double-start codons of them. Resembling AtTT2, BnTT2 proteins are nuclear-located R2R3-MYB proteins containing predicted DNA-binding sites, bHLH interaction residues, and transcription activation domains. Southern blot indicated that there might be three BnTT2 members in B. napus, lower than triplication-based prediction. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed that the expression of BnTT2-2 is mostly like AtTT2 with intensive expression in young seeds, but it is also expressed in root in which AtTT2 has no expression. BnTT2-1 shows lower tissue specificity and transcription levels, whereas BnTT2-3 is the lowest. Comparative cloning and RT-PCR indicated that seed color near-isogenic lines L1 and L2 have equivalent BnTT2 genes, and the yellow seed color in L2 might be caused by locus/loci other than BnTT2. Our results lay the basis for further investigating the regulatory mechanism of BnTT2 genes in flavonoid pathway and for transgenic creation of novel yellow-seeded B. napus stocks.

Amino Acid Sequence↗

Methylated A-type proanthocyanidins and related metabolites from Cassipourea gummiflua.

The range of natural dimeric A-type proanthocyanidins is extended by identification of two new dimeric afzelechins in the form of 7-OMe-epiafzelechin-(4 beta-->8,2 beta-->0-->7)- epiafzelechin and 7-OMe-epiafzelechin-(4 beta-->8, 2 beta-->0-->7)-ent-afzelechin. These are accompanied in the stem bark of Cassipourea gummiflua by the related metabolites afzelechin, kaempferol-3-0-alpha-L-rhamnopyranoside, afzelechin-3-0- alpha-L-rhamnopyranoside, epiafzelechin (4 beta-->8,2 beta-->0-->7)-epiafzelechin and epiafzelechin-(4 beta-->8, 2 beta-->0-->7)-ent-afzelechin, the latter three compounds being reported from a natural source for the second time.

Anthocyanins↗

Inhibitory activity of Jatropha multifida latex on classical complement pathway activity in human serum mediated by a calcium-binding proanthocyanidin.

This study isolates and characterizes the anti-complement constituent(s) present in the latex of Jatropha multifida, in an attempt to explain the traditional application of the latex in the treatment of infected wounds. Guided by the inhibition of classical pathway (CP) complement activity in human serum, a polymer was isolated which could be characterized as a proanthocyanidin. The polymer inhibits CP activation of the complement cascade, while alternative pathway (AP) activation is relatively insensitive to the polymer. This is due to the selective depletion of Ca2+, but not Mg2+, from the incubation medium.

Anthocyanins↗

Synthesis of modified proanthocyanidins: introduction of acyl substituents at C-8 of catechin. Selective synthesis of a C-4-->O-->C-3 ether-linked procyanidin-like dimer.

The regioselective introduction of substituents at C-8 of (+)-catechin is described, leading to the synthesis of several catechin derivatives with various substitution patterns to be used for the further synthesis of modified proanthocyanidins. Thereafter, a new 3-O-4 ether-linked procyanidin-like derivative was synthesized. Its formation was selectively achieved through TiCl(4)-catalyzed condensation of 4-(2-hydroxyethoxy)tetra-O-benzyl catechin with the 8-trifluoroacetyl adduct of tetra-O-benzyl catechin.

Antioxidants↗

Retention behavior of oligomeric proanthocyanidins in hydrophilic interaction chromatography.

A novel method was developed for the separation of proanthocyanidins (PAs; oligomeric flavan-3-ols) by hydrophilic interaction chromatography (HILIC) using an amide-silica column eluting with an aqueous acetonitrile mobile phase. The best separation was achieved with a linear gradient elution of acetonitrile-water at ratios of 9:1 to 5:5 (v/v) for 60 min at a flow rate of 1.0 ml/min. Under these HPLC conditions, a mixture of natural oligomeric PAs (from apple) was separated according to degree of polymerization (DP) up to decamers. The DP of each separated oligomer was confirmed by LC/electrospray ionization MS. In further HILIC separation studies of 15 different flavan-3-ol and oligomeric PA (up to pentamer) standards with an isocratic elution of acetonitrile-water (84:16), a high correlation was observed between the logarithm of retention factors (log k) and the number of hydroxyl groups in their structures. The coefficient of this correlation (r2=0.9501) was larger than the coefficient (r2=0.7949) obtained from the correlation between log k and log P(o/w) values. These data reveal that two effects, i.e. hydrogen bonding between the carbamoyl terminal on the column and the hydroxyl group of solute oligomer and hydrophilicity based on the high-order structure of oligomeric PAs, corporately contribute to the separation, but the hydrogen bonding effect is predominant in our HILIC separation mode.

Chromatography, High Pressure Liquid↗

Age associated changes in erythrocyte membrane surface charge: Modulatory role of grape seed proanthocyanidins.

Aging, a multifactorial process of enormous complexity is characterized by impairment of physio-chemical and biological aspects of cellular functions. It is closely associated with increased free radical production, which situation ultimately leads to devastation of normal cell function and membrane integrity. The present study was aimed to determine the effect of proanthocyanidins rich grape seed extract (GSP) on membrane surface charge density in erythrocytes during animal age associated oxidative stress. GSP (100 mg/day/kg body weight) was administered orally for 15 and 30 days to young and aged rats. Significant decrease in surface charge levels with concomitant increase in protein carbonyls and decrease in glycoprotein, antioxidants status was noted in erythrocytes of aged rats when compared with young rat erythrocytes. Duration dependent supplementation of GSP increased the erythrocyte surface charge density to near normalcy in aged rats. Decrease in protein carbonyls level and increase in glycoproteins as well as antioxidant status was observed in aged rat erythrocytes on GSP treatment. Thus, from our results, we conclude that GSP is an effective anti-aging drug in preventing the oxidative stress associated loss of membrane surface charge, which thereby maintains the erythrocyte membrane integrity and functions in elderly.

Aging↗