Protective Effect Of Proanthocyanidins Research Articles

The protective effect of proanthocyanidins on the psoriasis-like cell models via PI3K/AKT and HO-1

ABSTRACT Background Inflammation and oxidative stress (OS) are important contributors to psoriasis pathogenesis. Proanthocyanidins (PCs) have anti-inflammatory and anti-oxidative activities. Previously, we discovered that PCs alleviated psoriasis-like mice symptoms, likely via mitigating inflammation and OS damage. Objective To elucidate the protective mechanism underlying PCs against the damage of TNF-ɑ-induced psoriasis-like cell models. Methods Psoriasis-like cell models were established with 7.5 ng/mL TNF-ɑ and then subjected to different-concentrations PCs treatment. Finally, inflammatory and oxidative parameters were determined. Besides, LY294002 (PI3K inhibitor) and ZnPP (HO-1 inhibitor) were employed to investigate the roles of PI3K/AKT and HO-1 in PCs against psoriasis-like cell models. Results After TNF-α treatment, cells organized tightly and proliferated greatly (P<0.01); HO-1 expression dropped obviously, along with the increased OS/inflammatory indicators and the decreased antioxidants (P<0.05); consequently, psoriasis-like cell models were well established. In the presence of PCs, nevertheless, the proliferation rate and number of psoriasis-like cells evidently decreased (P<0.01), accompanied with enhanced HO-1 and antioxidants, and lowered OS/inflammatory indicators as well as phosphorylated JAK2/STAT3/PI3/AKT (P<0.01). Similar changes appeared after LY294002 pretreatment, regardless of PCs or not. But after ZnPP pretreatment with or without PCs, the opposite occurred. Conclusion The study reveals that PCs can suppress psoriasis-like cell proliferation and reduce inflammatory/OS damage through PI3K/AKT inhibition and HO-1 activation, thus promising a candidate for PCs in treating psoriasis.

Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats

Liver damage and fibrosis are serious health problems without effective treatment. Proanthocyanidins (PAs) are flavonoids with several biological effects. We investigated the potential anti-fibrotic effect of proanthocyanidins on carbon tetrachloride (CCl4)-induced liver injury and fibrosis. Liver fibrosis was induced by oral administration of CCl4 three times a week for 5 and 9 weeks. PAs were daily administered in a dose of 500 mg/kg bw. Animals were divided into five groups: control groups, olive oil-treated group, Pas-treated group, CCl4-treated animals, and PAs + CCl4-treated rats. CCl4 and PAs were administered by gavage. Administration of CCl4 caused a significant elevation in alanine aminotransferase and aspartate aminotransferase activities, the concentration of alpha-2-macroglobulin, and bilirubin concentration. In addition, the protein and apolipoprotein contents were significantly decreased in the serum of CCl4-treated rats. These results were accompanied by histopathological alterations and increased inflammation, apoptosis, and DNA damage. Treatment with PAs caused remarkable regression of fibrosis and alpha-2-macroglobulin with improvement in histological characteristics of the liver after 5 and 9 weeks of intoxication. PAs could also maintain redox balance, evidenced by the prevention of lipid peroxidation and mitigation of the decrease in antioxidants. Treatment of intoxicated rats with PAs resulted in a significant decline in pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α in serum. This is associated with a remarkable decrease in apoptosis of hepatic cells shown by decreased levels of Bax, caspase-3, and -9, with increased Bcl-2. The protective effect of PAs was also evident by protecting DNA integrity in the intoxicated rats. PAs suppressed hepatic fibrosis, improved liver function and structure via modulating the interdependence between oxidative stress, inflammation, apoptosis, and DNA integrity in CCl4-treated rats.

Proanthocyanidins alleviate pentylenetetrazole-induced epileptic seizures in mice via the antioxidant activity.

The role of oxidative stress in the initiation and progress of epilepsy is well established. Proanthocyanidins (PACs), a naturally occurring polyphenolic compound, have been reported to possess a broad spectrum of pharmacological and therapeutic properties against oxidative stress. However, the protective effects of proanthocyanidins against epilepsy have not been clarified. In the present study, we used the pentylenetetrazole (PTZ)-induced epilepsy mouse model to explore whether proanthocyanidins could help to reduce oxidative stress and protect against epilepsy. Mice were allocated into four groups (n = 14 per each group): control, PTZ (60mg/kg, intraperitoneally), PACs + PTZ (200mg/kg, p.o.) and sodium valproate (VPA) + PTZ (200mg/kg, p.o.). PTZ injection caused oxidative stress in the hippocampal tissue as represented by the elevated lipid peroxidation and NO synthesis and increased expression of iNOS. Furthermore, depleted levels of anti-oxidants, GSH, GR, GPx, SOD, and CAT also indicate that oxidative stress was induced in mice exposed to PTZ. Additionally, a state of neuroinflammation was recorded following the developed seizures. Moreover, neuronal apoptosis was recorded following the development of epileptic convulsions as confirmed by the elevated Bax and caspase-3 and the decreased Bcl2 protein. Moreover, AChE activity, DA, NE, 5-HT, brain-derived neurotrophic factor levels, and gene expression of Nrf2 have decreased in the hippocampal tissue of PTZ exposed mice. However, pre-treatment of mice with PACs protected against the generation of oxidative stress, apoptosis, and neuroinflammation in the PTZ exposed mice brain as the biomarkers for all these conditions was bought to control levels. In addition, the gene expression of Nrf2 was significantly upregulated following PACs treatment. These results suggest that PACs can ameliorate oxidative stress, neuroinflammation, and neuronal apoptosis by activating the Nrf2 signaling pathway in PTZ induced seizures in mice.

Protective Effect of Proanthocyanidin against Methotrexate-Induced Testicle Damage in Rats

Protective Effect of Proanthocyanidin against Methotrexate-Induced Testicle Damage in Rats

Protective effects of proanthocyanidins against cadmium-induced testicular injury through the modification of Nrf2-Keap1 signal path in rats

The purpose of this study was to evaluate the potential chemoprotective effects of proanthocyanidins (PAs) against cadmium (Cd)-induced oxidative damage of testes via Nrf2-Keap1 signal pathway in rats. Briefly, by using biochemical histological analysis, as well as the real time PCR and western blot approach, oxidative damage in rat testicular tissue was observed after exposure to Cd. In addition, significant down-regulations of mRNA and protein levels of nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), γ-glutamyl cysteine synthetase (γ-GCS), glutathione peroxidase (GSH-Px) and quinone oxidoreductase 1 (NQO1), as well as a significant up-regulation of Kelch sample related protein-1 (Keap1) levels in testicular tissue were observed after Cd exposure. Notably, these alterations were reverted back to near normalcy in Cd+PAs group rats. In conclusion, PAs exhibited a significant chemopreventive potential against Cd-induced testicular oxidative damage in rats, possibly through the modification of Nrf2-Keap1 signal path.

Proanthocyanidins prevent ethanol-induced cognitive impairment by suppressing oxidative and inflammatory stress in adult rat brain.

Excessive chronic alcohol consumption enhances brain oxidative and inflammatory stress, resulting in cognitive deficit. This study investigated the potential alleviating effects of proanthocyanidins (PACs) on ethanol-induced cognitive impairment and stress in brain regions including the prefrontal cortex, hippocampus, and amygdala. Adult male rats were administered saline, PACs, ethanol, or combinations of ethanol with different doses of PACs for 8 weeks. Then, the Morris water-maze test was performed. Thiobarbituric acid-reactive substances, superoxide dismutase activity, total antioxidant capacity, and nitric oxide were chosen as parameters of oxidative stress, whereas tumor necrosis factor-α and interleukin-1β chosen as parameters of inflammatory stress. The results indicated that ethanol led to cognitive impairment along with enhanced oxidative and inflammatory stress in brain regions, whereas PACs per se had no significant effects. Moreover, coadministration with PACs in ethanol-treated rats dose dependently rescued cognitive impairment accompanied by suppressed oxidative and inflammatory stress in brain regions. Thus, the protective effects of PACs on ethanol-induced cognitive impairments may be because of their antioxidant and anti-inflammatory activities.

Proanthocyanidin protects against cisplatin-induced oxidative liver damage through inhibition of inflammation and NF-κβ/TLR-4 pathway.

Although cisplatin (CIS) is a highly effective anticancer drug, hepatotoxicity is one of the most common adverse effects associated with its use. Recently, reactive oxygen species (ROS) and inflammation are suggested to be key factors in the pathophysiology of CIS-induced acute liver damage. The aim of this study is to investigate the possible protective effect of proanthocyanidin (PRO) against CIS-induced acute hepatotoxicity. Rats were divided into four groups: 1, Control; 2, PRO; 3, CIS; and 4, PRO + CIS. Biochemical studies and histopathology were used to assess liver damage. ROS, inflammatory cytokines, nuclear factor kappa beta (NF-κβ), inducible cyclooxygenase enzyme (COX-2), inducible nitric oxide synthase (iNOS), toll-like receptor-4 (TLR-4) gene expression, and apoptotic markers were also assessed. PRO pretreatment protected the liver against CIS-induced toxicity as indicated by decreased plasma levels of liver function enzymes and the normal liver histopathology observed in the PRO + CIS group. PRO pretreatment also diminished indicators of oxidative stress in the liver, including nitric oxide (NO) and malondialdehyde (MDA). It also increased the antioxidants, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in the liver. Plasma interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) were all reduced. Liver gene expression of NF-κβ, COX-2, iNOS, and TLR-4 were all downregulated. Furthermore, PRO administration downregulated the liver expression of the apoptotic marker, Bax, while upregulated the antiapoptotic marker, Bcl2. In conclusion, our results revealed that PRO may protect against CIS-induced acute liver damage mainly through inhibition of ROS, inflammation, and apoptosis.

Protective Effect of Proanthocyanidins from Sea Buckthorn (Hippophae Rhamnoides L.) Seed against Visible Light-Induced Retinal Degeneration in Vivo.

Dietary proanthocyanidins (PACs) as health-protective agents have become an important area of human nutrition research because of their potent bioactivities. We investigated the retinoprotective effects of PACs from sea buckthorn (Hippophae rhamnoides L.) seed against visible light-induced retinal degeneration in vivo. Pigmented rabbits were orally administered sea buckthorn seed PACs (50 and 100 mg/kg/day) for 14 consecutive days of pre-illumination and seven consecutive days of post-illumination. Retinal function was quantified via electroretinography 7 days after light exposure. Retinal damage was evaluated by measuring the thickness of the full-thickness retina and outer nuclear layer 7 days after light exposure. Sea buckthorn seed PACs significantly attenuated the destruction of electroretinograms and maintained the retinal structure. Increased retinal photooxidative damage was expressed by the depletion of glutathione peroxidase and catalase activities, the decrease of total antioxidant capacity level and the increase of malondialdehyde level. Light exposure induced a significant increase of inflammatory cytokines (IL-1β, TNF-α and IL-6) and angiogenesis (VEGF) levels in retina. Light exposure upregulated the expression of pro-apoptotic proteins Bax and caspase-3 and downregulated the expression of anti-apoptotic protein Bcl-2. However, sea buckthorn seed PACs ameliorated these changes induced by light exposure. Sea buckthorn seed PACs mediated the protective effect against light-induced retinal degeneration via antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Effects of Proanthocyanidins on Intestinal Motility Disturbance Following Intestinal Ischemia/Reperfusion

ABSTRACTPurpose: To investigate the potential protective effects of Proanthocyanidins(PAs) on intestinal motility disturbance following intestinal ischemia/reperfusion (I/R). Materials and Methods: Male rats were divided into four groups: Sham, I/R, I/R+PA100 and I/R+PA200. Sham group underwent laparotomy without ligation, the others were subjected to intestinal ischemia for 1 h and reperfusion 4 h. Rats in the I/R+PA100 group received PAs (100 mg/kg/d) for 5 days prior to I/R, while rats in the I/R+PA200 group received PAs (200 mg/kg/d). After reperfusion, using an electrophysiology instrument measured ileal slow wave. Ileal specimens were obtained to determine contractility, tissue levels of Bax, Bcl-2, and Caspase-3 and evaluate histopathological changes. In addition, blood sample was obtained to determine serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels. Results: Intestinal I/R caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, and hemorrhage. Both PAs treatment decreased mucosal pathological impairment in comparison with the I/R group (p < .05) in light microscopic evaluations. In both PAs-treated groups, Bax and Caspase-3 expression were decreased compared to I/R group, while the Bcl-2 expression increased (p < .05), which was similarly the case for serum SOD activity demonstrated significant enhance (p < .05) and decline in MDA levels in comparison with I/R group (both p < .05). Moreover, PAs treatment was more efficient in attenuating serum MDA levels of intestinal I/R (both p < .05). And the contractile amplitude and frequency of slow wave in I/R+PA100 and I/R+PA200 groups were higher than I/R group (both p < .05). Conclusions: PAs improve intestinal motility disturbance following intestinal I/R by alleviating oxidative stress and apoptosis.

Protective effect of proanthocyanidins against myocardial damage induced by mechanical trauma in rats

Objective To evaluate the effect of proanthocyanidins on cardiocyte apoptosis and cardiac dysfunction following mechanical trauma (MT) in rats and discuss its mechanism. Methods A total of 120 SD rats were allocated to normal group, trauma group, and trauma solvent group (treated with proanthocyanidins) and trauma vehicle group (treated with saline solution) according to the random number table, with 30 rats per group. Small animal quantitative wound instrument was used to prepare the MT model in rats. Cardiocyte apoptosis was measured by TUNEL staining. Changes in left ventricular diastolic pressure were recorded by left ventricular intubation via the right common carotid artery. Reactive oxygen species (ROS) produced by H9c2 cells before and after proanthocyanidins administration was detected with flow cytometry. Level of Ca2+ in cardiocytes marked by Fluo-4AM was determined with laser scanning confocal microscope. Ultrastructure changes in cardiocytes were observed under electronic microscope. Results After the induction of MT, apoptosis index of cardiocytes in trauma group, trauma solvent group and trauma vehicle group was (7.96±1.16)%, (2.44±0.70)%, and (7.76±1.14)% respectively, far higher than (0.64±0.59)% in normal group (P 0.05) but substantial reduction was detected in trauma solvent group (P<0.05). The + dp/dtmax of cardiac function in trauma and trauma vehicle groups was (3294.55±180.95)mmHg/s and (3337.80±220.11)mmHg/s respectively lowered from (4030.04±293.70) mmHg/s in normal group (P<0.01), and was (3926.72±364.95)mmHg/s in trauma solvent group lowered in contrast with trauma group (P<0.05). The -dp/dtmax in trauma and trauma vehicle groups was (2294.55±298.69)mmHg/s and (2291.20±348.72)mmHg/s respectively lowered significantly from (2830.04±334.63) mmHg/s in normal group (P<0.05), and was (2801.52±266.25)mmHg/s increased significantly in contrast with trauma group (P<0.05). Compared with normal group, trauma group showed chromatin margination and condensation as well as marked vacuolization in the epithelium from intramuscular capillaries. However, the pathological changes were improved after proanthocyanidins therapy. Conclusion Proanthocyanidins is effective in heart protection after the mechanical trauma by attenuating the pathological changes of myocardial ultrastructure and myocardial apoptosis and improving cardiac function. Key words: Proanthocyanidins; Heart injuries; Oxidative stress

Protective effect of proanthocyanidin against oxidative ovarian damage induced by 3-nitropropionic acid in mice

Oxidative stress, which poses a threat to reproductive health, causes many serious female reproductive diseases. In this study, we investigated whether proanthocyanidins (PC) have a protective effect against oxidative stress-induced ovarian damage. Forty female ICR mice were randomized into 4 groups: a control group, a control plus PC group, a 3-nitropropionic acid (3-NPA) group, and a 3-NPA plus PC group. An ovarian oxidative stress model induced by 3-NPA was constructed using female ICR mice. After the animals were sacrificed, their ovaries were collected to measure reactive oxygen species (ROS) levels, the activities of superoxide dismutase (SOD) and catalase (CAT), and the mRNA expression levels of relevant granulosa cell apoptosis genes (Bcl-2, Bax, Bim, FasL, and caspase-3). We also conducted a histological evaluation of granulosa cell apoptosis and follicular atresia. The results showed that compared to the 3-NPA group, ROS levels and activities of T-SOD and CAT in the 3-NPA plus PC group were significantly decreased (P < 0.05), while the ratio of Bcl-2 to Bax in the 3-NPA plus PC group were significantly increased (P < 0.05). mRNA expression levels of Bim, FasL, and caspase-3 in the 3-NPA plus PC group were significantly decreased (P < 0.05), and the percentage of atretic follicles and granulosa cell apoptosis in the 3-NPA plus PC group was significantly decreased (P < 0.05). Collectively, these data indicate that PC has significant protective effects against damage induced by oxidative stress in mouse ovaries. The mechanisms of protection may be related to antioxidation and apoptosis reduction.

Protective effects of proanthocyanidins on intestinal smooth muscle contractility in rats with intestinal ischemia-reperfusion injury

Protective effects of proanthocyanidins on intestinal smooth muscle contractility in rats with intestinal ischemia-reperfusion injury

Protective Effect of Proanthocyanidins in Cadmium Induced Neurotoxicity in Mice.

Cadmium (Cd) is a potent neurotoxic heavy metal, known to induce oxidative stress and membrane disturbances in brain. Proanthocyanidins (PACs), the most abundant polyphenol class in the human diet, have protective effects on oxidative stress and other metabolic disorders. Based on the cellular protective effect of PACs, we aimed to investigate whether PACs could protect the neuronal cells from Cd-induced excitotoxicity. The experiment was carried out on mice model and also in primary culture of hippocampal neurons isolated from neonatal mice. The Cd-induced changes in acetylcholinesterase (AChE) activity, oxidative stress markers (lipid peroxidation/lipid hydroperoxidation), antioxidant status and Akt phosphorylation were measured in the mice brain with or without PACs treatment. Mice intoxicated with cadmium (5 mg/kg/day) for 4 weeks had significantly (p<0.05) reduced the AChE levels, elevated the levels of oxidative stress markers along with the significant (p<0.05) decrease in the levels of both enzymatic antioxidants and non-enzymatic antioxidants in mice brain tissue. In contrast, administration of PACs (100 mg/kg/day) for 4 weeks in cadmium-intoxicated mice had significantly (p<0.05) protected the cadmium-mediated changes. In addition, PACs treatment in cultured mice hippocampal neurons had protected Cd-induced excitotoxicity by activating Akt phosphorylation, decreasing the caspase-3 level and improving the neuronal cell survival rate up to 24 h. Altogether, our data suggest that PACs plays a crucial role on neuroprotection in combating the cadmium induced oxidative neurotoxicity in mice brain by influencing the activation of AChE/Akt phosphorylation, antioxidant status, controlling the membrane damage (lipid peroxidation) and apoptotic protein caspase-3.

Protective effects of proanthocyanidin and vitamin E against toxic effects of formaldehyde in kidney tissue

We investigated possible effects of proanthocyanidin (PA) and vitamin E on damage to rat kidneys induced by formaldehyde (FA), using biochemical characteristics and light and electron microscopy. Male rats were divided into control, FA, PA and vitamin E treated groups. Kidney tissue was observed by light and electron microscopy. Bcl-2/Bax rate was measured using immunohistochemistry. Malondialdehyde (MDA) and total sialic acid (TSA) levels, superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase (CAT) and myeloperoxidase (MPO) activities were measured. We found that FA caused damage to the parietal epithelial layer of the glomerulus, mononuclear cell infiltration, membrane damage in renal tubules, pyknotic nuclei, hypertrophic cells in Henle's loop and tubules, and loss of renal tubule integrity. We also observed invagination of the nuclear membrane, irregularity of chromatin material and loss of mitochondrial cristae. We observed increased Bcl-2 and Bax immunostaining in the FA group, but the Bcl-2/Bax rate remained unchanged in FA, PA and vitamin E groups compared to controls. Tissue MDA and TSA levels, and CAT and Gpx activities were increased, and SOD and MPO activities were decreased by FA toxicity. We observed a protective effect of PA in tissue MDA and TSA levels and SOD activities, because there was no difference in the PA group compared to the control group. We investigated the antioxidant effects of PA and vitamin E and found protective effects of PA against apoptosis.

Protective Effect of Proanthocyanidin against Diabetic Oxidative Stress

We investigated the antidiabetic potential of proanthocyanidin and its oligomeric form in STZ-induced diabetic model rats and db/db type 2 diabetic mice. Proanthocyanidin ameliorated the diabetic condition by significant decreases of serum glucose, glycosylated protein, and serum urea nitrogen as well as decreases of urinary protein and renal-AGE in STZ-induced diabetic rats and decrease of serum glucose as well as significant decrease of glycosylated protein in db/db type 2 diabetic mice. The suppression of ROS generation and elevation of the GSH/GSSG ratio were also observed in the groups administered proanthocyanidin. Moreover, proanthocyanidin, especially its oligomeric form, affected the inflammatory process with the regulation of related protein expression, iNOS, COX-2 and upstream regulators, NF-κB, and the IκB-α. In addition, it had a marked effect on hyperlipidemia through lowering significant levels of triglycerides, total cholesterol, and NEFA. Moreover, expressions in the liver of SREBP-1 and SREBP-2 were downregulated by the administration of proanthocyanidins. The protective effect against hyperglycemia and hyperlipidemia in type 1 and 2 diabetic models was significantly strong in the groups administered the oligomeric rather than polymeric form. This suggests that oligomers act as a regulator in inflammatory reactions caused by oxidative stress in diabetes.

Protective Effects of Proanthocyanidin on Cerulein-induced Acute Pancreatic Inflammation in Rats.

BackgroundThe aim of this study was to assess the possible protective effect of proanthocyanidin against cerulein-induced acute pancreatic inflammation (AP) and oxidative injury.MethodsSprague-Dawley rats were pretreated with proanthocyanidine (100 mg/kg, orally) or saline 15 min before cerulein was given by 20 µg/kg subcutaneously at 1-h intervals within 4 hours. Six hours after cerulein or saline injections, the animals were killed by decapitation. Blood samples were collected to analyze amylase, lipase, and proinflammatory cytokines (TNF-α and IL-1b). Pancreas tissues were taken for the determination of tissue glutathione (GSH) and malondialdehyde (MDA) levels, Na+, K+-ATPase and myeloperoxidase (MPO) activities. Formation of reactive oxygen species in pancreatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes, while the extent of tissue injury was analyzed microscopically.ResultsAcute pancreatitis caused a significant decrease in tissue GSH level and Na+, K+-ATPase activity, which was accompanied with significant increases in the pancreatic MDA, luminol and lucigenin chemiluminescences (CL) levels and MPO activity. Similarly TNF-α and IL-1β levels were elevated in the pancreatic group as compared to control group. On the other hand, proanthocyanidin treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by cerulein.ConclusionsProanthocyanidine can ameliorate pancreatic injury induced by cerulein in rats, this result suggests that proanthocyanidin may have utility in treating acute pancreatititis.

Effects of Proanthocyanidin Preparations on Hyperlipidemia and Other Biomarkers in Mouse Model of Type 2 Diabetes

The protective effect of proanthocyanidins from persimmon peel, using both oligomers and polymers, was investigated in a db/db type 2 diabetes model. Male db/db mice were divided into three groups: control (vehicle), polymer-, or oligomer- (10 mg/(kg body weight x day x p.o.)) administered mice. Age-matched nondiabetic m/m mice were used as a normal group. The administration of proanthocyanidins reduced hyperglycemia in db/db mice through a decline in the serum level of glucose and glycosylated protein. In addition, it had a strong effect on hyperlipidemia through lowering levels of triglyceride, total cholesterol, and nonesterified fatty acids. The protective effect against hyperglycemia and hyperlipidemia was greater in the groups administered the oligomeric rather than polymeric form. The increased oxidative stress in db/db mice was attenuated by the administration of oligomers through inhibiting the generation of reactive oxygen species and lipid peroxidation and elevating the reduced glutathione/oxidized glutathione ratio. On the other hand, polymers did not show such an effect. Moreover, expressions in the liver of sterol regulatory element binding protein (SREBP)-1 and SREBP-2 were downregulated by the administration of proanthocyanidins, especially the oligomeric form. Oligomers caused a slight elevation in the expression of peroxisome proliferator-activated receptors alpha. Furthermore, oligomeric proanthocyanidin regulated the expression of nuclear factor kappaB in db/db type 2 diabetes via the activation of inhibitor protein kappaB-alpha. It also attenuated the protein expressions of cyclooxygenase-2 and inducible nitric oxide synthase. This suggests that oligomers would act as a regulator in inflammatory reactions associated with oxidative stress in type 2 diabetes. The present study results suggest that proanthocyanidin administration, especially the oligomeric form, may improve oxidative stress via the regulation of hyperlipidemia than hyperglycemia in type 2 diabetes.

Properties of grape seed proanthocyanidins and quercetin in human lymphocytes

This study addresses the in vitro protective effects of proanthocyanidins and quercetin on the frequency of micronuclei with reference to the antioxidant status of cultured human lymphocytes also subjected to 2 Gy of ?-radiation. Treatment of lymphocytes with proanthocyanidins induced a significant decrease in the frequency of micronuclei and reduction of malonyldialdehyde production, as well as increased catalase and glutathione S-transferase activity. Quercetin induces a higher incidence of micronuclei and production of malonyldialdehyde. The seven-fold increase of micronuclei frequency induced by a therapeutic dose of ?-radiation was decreased in the presence of proanthocyanidins. These results demonstrate that proanthocyanidins may be important in the prevention of ROS-induced oxidative lymphocyte damage by decreasing DNA damage, lowering membrane lipid peroxidation, and increasing the activity AOP enzymes, as well as by reducing the level of ?-radiation-induced DNA damage. Our results support the potential benefits of proanthocyanidins as efficient antioxidants and radioprotectors.

The protective effect of proanthocyanidin on the methotrexate-induced intestinal damage

19576 Background: Methotrexate (MTX) induced mucositis is an important dose-limiting side effect for which there is no definitive prophylaxis or treatment. This study was designed to investigate whether proantocyanidin, grape seed extract from Vitus Vinifera, had a protective effect on the small intestine of rats with MTX-induced damage. Methods: Thirty two albino rats were randomized into experimental and control groups and divided into four groups. To the first group, MTX was applied as a single dose (20 mg/kg) intraperitoneally. To the second group, in addition to MTX application, proanthocyanidin (100 mg/kg) was given orally every day by gavage until the rats were killed. To the third group, proanthocyanidin only was administered. The fourth group was the control. All animals were sacrificied 4 days after the intraperitoneally injection of MTX for histopathologic examination and tissue malonaldehyd (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. Results: MTX was found to lead to injury in the jejunal tissues and to increase the MDA levels. Administration of the proantocyanidin decreased the jejunal damage and MDA level which was caused by MTX treatment and increased SOD an GPx levels. Conclusions: These results suggest that proanthocyanidin may protect the small intestine of rats from MTX-induced damage. The effects of proanthocyanidin could be resulted from antioxidant properties of the proanthocyanidin. No significant financial relationships to disclose.