Grape Seed Extract

BACKGROUND: The bidirectional relationship between periodontitis and type 2 diabetes (T2D) underscores the need for adjunctive therapies to enhance nonsurgical periodontal therapy (NSPT). This meta-analysis evaluates the efficacy of antioxidants in improving periodontal and glycemic outcomes in T2D patients with periodontitis. MATERIAL AND METHODS: A systematic literature search was conducted using PubMed, Embase, Scopus, Web of Science, and Google Scholar, covering publications from 2015 to 2025. Antioxidants tested were melatonin, propolis, lycopene, ginger, vitamin C, omega-3 fatty acids (O3FAs), and grape seed extract. Outcomes (clinical attachment level [CAL], probing depth [PD], gingival index [GI], HbA1c) were analyzed using random-effects models (mean differences, 95% CIs). Risk of bias was assessed via the Cochrane criteria. RESULTS: Eight randomized controlled trials (RCTs, n = 315) were identified. Adjunctive antioxidants significantly improved CAL (melatonin: SMD -2.28, 95% CI -3.01 to -1.56; propolis: SMD -3.83, -4.79 to -2.87) and PD (melatonin: SMD -2.40, -3.14 to -1.66; propolis: SMD -1.78, -2.44 to -1.11). Melatonin and propolis also reduced HbA1c (melatonin: SMD -2.28; propolis: SMD -3.83). Lycopene and ginger showed modest effects, while vitamin C and O3FAs had minimal impact. Evidence certainty was moderate for CAL/HbA1c and low for PD/GI. CONCLUSION: Antioxidants, particularly melatonin and propolis, enhance periodontal and glycemic outcomes in T2D-periodontitis patients. Despite promising results, limitations include small sample sizes and heterogeneity. Larger RCTs are needed to optimize protocols. © 2025 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

The objective of this systematic review and meta-analysis of controlled trials was to assess the long-term effect of grape seed extract (GSE) supplementation on flow-mediated dilation (FMD), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) in adults. Web of Science, Scopus, Medline, Cochrane Library, and Google Scholar were searched up to May 24, 2021. Nineteen trials were included in this study. Weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using a random-effects model. GSE supplementation significantly reduced DBP (WMD: -2.20 mmHg, 95% CI: -3.79 to -0.60, I2 = 88.8%) and HR (WMD: -1.25 bpm, 95% CI: -2.32 to -0.19, I2 = 59.5%) but had no significant effects on FMD (WMD: 1.02%, 95% CI: -0.62 to 2.66, I2 = 92.0%) and SBP (WMD: -3.55 mmHg, 95% CI: -7.59 to 0.49, I2 = 97.4%). Subgroup analysis revealed that the dose and duration of GSE administration and the characteristics of study participants could be sources of between-study heterogeneity. Significant non-linear relationships were found between DBP and the duration of GSE supplementation (P = 0.044) and its dose (P = 0.007). In conclusion, GSE may be beneficial for individuals with or at risk of cardiovascular disease because it may have hypotensive and HR-lowering properties.

BACKGROUND: Grape seed extract (GSE) seems to have antioxidant and anti-inflammatory properties due to its high polyphenolic content. Nevertheless, the scientific literature in this field is controversial and inconclusive. Therefore, we aimed to conduct a systematic review and meta-analysis of controlled trials to evaluate the effect of supplementation with GSE on biomarkers of oxidative stress and inflammation. METHODS: Medline, Scopus, Cochrane Library, Google Scholar and Web of Science databases were searched up to 10 September 2020 using appropriate keywords without restrictions. In the systematic review phase, all biomarkers of oxidative stress and inflammation were considered as outcomes. In the meta-analysis phase, six biomarkers were selected as outcomes, and weighted mean difference (WMD) or standardised mean difference (SMD) with 95% confidence interval (CI) was calculated for them using a random-effects model. RESULTS: Twenty-three studies were included in the systematic review, and 19 studies were included in the meta-analysis. GSE supplementation caused a significant decrease in malondialdehyde (SMD: -1.04, 95% CI: -1.65, -0.42), oxidised low-density lipoprotein (SMD: -0.44, 95% CI: -0.75, -0.13) and high-sensitivity C-reactive protein (WMD: -0.48 mg/L, 95% CI: -0.94, -0.03) and a marginally significant increase in total antioxidant capacity (SMD: 0.49, 95% CI: -0.05, 1.04) but did not significantly influence C-reactive protein (WMD: -0.36 mg/L, 95% CI: -1.02, 0.30) and white blood cell count (WMD: 0.12 × 109 /L, 95% CI: -0.25, 0.48). CONCLUSION: It appears that GSE supplementation can remarkably modulate the body's redox system, particularly through the inhibition of lipid peroxidation, but has neutral or mildly beneficial effects on inflammatory responses. © 2021 John Wiley & Sons Ltd.

Although grape polyphenols can decrease chronic inflammations, their effect on C-reactive protein (CRP) levels is still controversial. So, this meta-analysis was conducted to investigate the effect of grape products containing polyphenols on CRP concentrations. In order to collect the relevant randomised controlled trials (RCT), the databases of PubMed, Scopus, Web of Science and Google Scholar were searched up to 30 March 2020. The random effects model, standardised mean difference (SMD) and 95 % CI were applied in data analysis. Meta-analysis was conducted over seventeen eligible RCT containing a total of 668 participants. The study registration number is CRD42018110169. Based on the results, grape products containing polyphenols decreased CRP levels significantly (SMD = −0·229; 95 % CI −0·41, −0·05; P = 0·013). Sensitivity analysis was performed by removing each individual study and the results did not change. According to the subgroup analysis, higher doses of grape polyphenols (>500 mg/d) and longer intervention periods (≥12 weeks) had significant effects on CRP levels. Furthermore, grape polyphenols significantly reduced the CRP levels in patients with a clinical condition. In the same vein, grape seed extract and other grape products, such as grape extract, juice and raisins, decreased CRP levels significantly. According to the meta-regression results, the CRP level depends on the dose and duration of the grape polyphenol supplementation. Based on the findings, grape products containing polyphenols had a significant effect on CRP levels. Further well-designed and long-term clinical trials are highly recommended to achieve more comprehensive and accurate results.

Dyslipidemia is a modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). Chardonnay marc, the residual by-product of winemaking, is an underutilized agricultural product that remains rich in extractable and non-extractable nutrients, including polyphenolics (e.g., flavan-3-ols) and fiber, which may beneficially influence plasma lipids. This study evaluated whether ingestion of Chardonnay grape seed extract/marc blends could improve plasma lipids in adults with dyslipidemia. We hypothesized that a Chardonnay marc-rich blend (HM) would reduce total cholesterol and LDL-cholesterol (LDL-c), while a Chardonnay seed extract-rich blend (HE) would reduce total cholesterol, LDL-c, and triglycerides, without affecting HDL-cholesterol (HDL-c) or endothelial function. Twenty-four adults with mild dyslipidemia completed a 16-week randomized, double-blind, crossover trial involving three 3-week intervention periods (consuming 1500 mg of HM, HE, or microcrystalline cellulose (MCC)), each followed by a 3-week washout. Systolic blood pressure was significantly lower following HE (118.8 ± 2.8 mmHg) compared to HM (125.6 ± 2.5 mmHg). HDL-c concentrations were higher after HM (56.6 ± 2.6 mg/dL) and MCC (55.7 ± 2.5 mg/dL) compared with HE (52.4 ± 2.5 mg/dL), and the number of large HDL particles was lower following HE (7.1 ± 0.7 µmol/L) compared with MCC (7.7 ± 0.7 µmol/L). Additionally, postprandial triglyceride area under the curve was lower after HM compared with HE. These findings suggest that the broader nutrient complexity of Chardonnay marc may offer pleiotropic benefits for modifiable ASCVD risk factors (ClinicalTrials.gov: NCT03203915). Published by Elsevier Inc.

BACKGROUND/AIM: There is increasing evidence for recognition of nutraceuticals as anti-tumour agents in various cancers. Over the years, anecdotal reports and our laboratory-based research have indicated their promising therapeutic potential for the management of glioblastoma. The aim of this study was to assess the effect of a combination of 7 micronutrients on overall survival of these patients. PATIENTS AND METHODS: A Nutraceutical study was conducted at King's College and St Thomas' Hospitals, London. Fifty-three newly diagnosed patients (37 males and 16 females) with glioblastoma were recruited consecutively in this randomised entry, double blind Phase II trial. The treatment (containing chokeberry extract, red grape seed extract, red clover extract, curcumin, selenium, tangeretin and lycopene) was given to two-thirds of the patients for 1 year after neurosurgery. This was consistent with the start date of their concomitant Stupp Protocol chemoradiation therapy. The patients in the placebo group had identical capsules which contained lactose only. RESULTS: Although the Kaplan - Meier analysis showed that the overall survival for the active and placebo groups was 14 and 13 months respectively, the results were not statistically significant (p=0.752). CONCLUSION: This study has limitations but it acts as a proof of principle towards larger studies, as clearly sufficiently powered trials are crucial in determining the nature and size of the treatment effect. Future trials should consider subgroup analysis, with respect to such factors as patient's age at diagnosis, gender, extent of surgery, MGMT mutation and IDH status to identify the optimal responders.

BACKGROUND: Varicose veins affect 25% to 40% of adults, with higher prevalence in older populations. Although Vitis vinifera seed extract (VVSE) can alleviate symptoms of venous insufficiency, its effects on venous reflux remain uncertain. We hypothesized that oral VVSE supplementation would significantly reduce venous reflux time compared with lifestyle modifications alone in patients with lower extremity varicose veins. METHODS: This prospective, open-label, randomized controlled trial enrolled adults aged 19 to 80 years with varicose veins and venous reflux confirmed by Doppler ultrasound (≥0.5 seconds in superficial veins or ≥1 second in deep veins). Patients were provided oral VVSE (150 mg twice daily) plus therapeutic lifestyle changes or therapeutic lifestyle changes alone (control) over 12 weeks. The mean venous reflux time, changes in specific vein reflux times, proportion achieving improved reflux (≤0.5 seconds for superficial veins, ≤1 second for deep veins), Venous Clinical Severity Score (VCSS), and Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ-14) score were compared. RESULTS: Among 176 participants (88/group), the VVSE group experienced significantly greater reductions in mean venous reflux time. Improvements were observed in both superficial and deep veins, with notable effects in the great saphenous and popliteal veins. The proportion of patients achieving improved venous reflux was significantly higher in the VVSE group. The VVSE group also demonstrated superior symptom improvement, with greater reductions in VCSS and CIVIQ-14 scores. CONCLUSIONS: VVSE significantly reduced venous reflux time across both superficial and deep veins, improving patient-reported symptoms compared with lifestyle modifications alone. The beneficial effects were consistent across diverse patient subgroups and particularly noteworthy in deep venous insufficiency.

BACKGROUND: This study aimed to assess the radiological and clinical outcomes of mineral trioxide aggregates (MTA) versus grape seed extract (GSE) when used as a dressing material in primary teeth undergoing pulpotomy. METHODS: This was a prospective split-mouth randomized clinical study. A total of 32 primary teeth were included and split into 2 groups: MTA was used in group I, and GSE was used in group II. A clinical and radiographic follow-up was conducted for 6 months postoperatively. Periapical radiographs were taken for all treated teeth at 3- and 6-month follow-up visits. Radiographic criteria for clinical success included absence of internal resorption, pathologic external resorption, interradicular radiolucency, periapical radiolucency, and widening of the periodontal ligament space. RESULT: In the MTA group, clinical and radiographic success was 100% at 1 and 3 months, in comparison to 93.75% 6 months postoperatively. In the GSE group, clinical success was 100% 1 month, and 93.75% 3 and 6 months postoperatively, while radiographic success was 100% at 3 months, 87.5% 6 months postoperatively. There were no significant statistical differences in the overall clinical or radiographic outcomes between the study groups (P > .05). CONCLUSION: Both MTA and GSE are associated with successful clinical and radiographic outcomes of pulpotomy; however, MTA seems to be associated with reduced inflammatory reactions, rendering it more effective than GSE.

BACKGROUNDS: Evidence indicated that an increase in nitric oxide (NO) bioavailability via dietary supplementation decreased sympathetic output. Grape seed extract (GSE) supplement has been known to increase NO production and improve endothelial function in individuals with elevated and stage 1 hypertension (ES1H), but no studies have assessed the effects of this extract on autonomic balance. Accordingly, the aim of the study was to investigate the effect of 7 days of dietary GSE supplementation on cardiac autonomic and hemodynamic responses. METHODS: Ten males were recruited in this study. Each subject received GSE or placebo supplementation with a 1-week wash-out period. In a double-blinded, cross-over design, hemodynamic responses (heart rate (HR), stroke volume (SV), cardiac output (CO), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean atrial pressure (MAP)), heart rate variability (HRV), and cold pressor test (CPT) were compared before and after either GSE or placebo supplementation. RESULTS: Our results indicated that GSE decreased resting DBP (75 ± 2 vs. 71 ± 3) and MAP (91 ± 2 vs. 88 ± 3) compared to the placebo (DBP:71 ± 3 vs. 74 ± 3; MAP: 89 ± 2 vs. 90 ± 2). However, MAP responses to CPT had no difference between post-PL and post-GSE supplementation when expressed as absolute increases (PL, Δ10.3 ± 1 mmHg, GSE, Δ9.1 ± 1 mmHg). There were no differences on the HR, SV, CO, SBP, and HRV between placebo and GSE treatments. CONCLUSIONS: Our study suggests that GSE can be used as a dietary nutraceutical capable of reducing blood pressure and the risk of ES1H development. The reduction of blood pressure occurs via peripheral vasodilation, not associated with cardiac autonomic reactivity. © 2025 The Author(s). Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.

BACKGROUND AND AIMS: Antioxidants, including vitamin E (VE) and grape seed extract (GSE), as anti-aging supplementation have been widely used to improve human health. The gut microbiota plays a crucial role in health and affects the treatment effect of various interventions. However, the role of gut microbiota in VE remains unclear. This study aimed to assess the longitudinal impact of VE treatment on body health and the gut microbiota. METHODS AND RESULTS: A randomized controlled trial was conducted with 90 healthy individuals. The participants were randomly assigned to three groups: a treatment group receiving VE, another antioxidant treatment group receiving GSE, and a control group receiving a placebo. We found that VE ameliorated blood cholesterol levels by reducing the levels of low-density lipoprotein cholesterol (LDL-C) in healthy volunteers. After the intervention, there was an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria and bile acid metabolizers. Specifically, the abundances of Lachnospira sp. and Faecalibacterium spp. increased in the VE. Interestingly, the gut microbiota of poor responders harbored a greater proportion of disease-associated bacterial species. CONCLUSIONS: VE could promote health by lowering LDL-C, partly and indirectly by affecting gut bacteria with the ability to produce SCFAs or metabolize bile acids. REGISTRATION NUMBER FOR CLINICAL TRIALS: The clinical trial was registered on August 28, 2021. Registration number was ChiCTR2100050567 (https://www.chictr.org.cn).

BACKGROUND: Postpartum hemorrhage (PPH) is one of the three leading causes of maternal mortality. Herbal medicine is one of the well-known methods of treatment in the world. OBJECTIVE: This study was conducted to determine and compare the effect of dates, grape seed and dill seed extracts on the PPH rate in women in the fourth stage of labor. METHODS: Two hundred eligible multiparous women visiting the maternity ward in Hamadan for normal delivery participated in this double-blind parallel-group clinical trial. They were randomly divided into four 50-member groups of experiment (3 groups) and control (1 group). The data were collected using a researcher-made questionnaire. In the experimental groups, in addition to routine care and oxytocin administration, the mothers received a capsule containing 15 mg of dill seeds extract or 20 mg of grape seed extract or 5 g of dates extract immediately after the delivery, and then their hemorrhage rates were measured one and two hours after delivery. The control group received routine care, oxytocin, and placebo. Data were analyzed in SPSS 21. RESULTS: The hemorrhage changes in the placebo group were much less than the intervention groups at 1 and 2 hours after delivery, and the four groups had a significant difference in terms of hemorrhage in both hours (p <0.001). The overall difference between the dates extract group and the placebo and grape seed groups was also statistically significant (p <0.05). CONCLUSION: All three extracts of dates, grape seed and dill seeds, especially dates, can be effective in PPH reduction.

BACKGROUND: Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was noninferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease. METHODS: In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score at 4 and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline. RESULTS: In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant intergroup difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval -1.65 to 5.72). The lower limit of the 95% confidence interval was within the predefined noninferiority margin of 6.9. Furthermore, the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score scores significantly decreased at 4 and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract. CONCLUSIONS: Vitis vinifera seed extract was noninferior to MPFF in relieving v

BACKGROUND: Despite the high antioxidant potential of grape seed extract (GSE), very limited studies have investigated its effect on non-alcoholic fatty liver disease (NAFLD). Therefore, this study was conducted with the aim of investigating the effect of GSE on metabolic factors, blood pressure and steatosis severity in patients with NAFLD. METHODS: In this double-blind randomized clinical trial study, 50 NAFLD patients were divided into two groups of 25 participants who were treated with 520 mg/day of GSE or the placebo group for 2 months. The parameters of glycemic, lipid profile, blood pressure and steatohepatitis were measured before and after the intervention. RESULTS: The GSE group had an average age of 43.52 ± 8.12 years with 15 women and 10 men, while the placebo group had an average age of 44.88 ± 10.14 years with 11 women and 14 men. After 2 months of intervention with GSE, it was observed that insulin, HOMA-IR, TC, TG, LDL-c, ALT, AST, AST/ALT, SBP, DBP and MAP decreased and QUICKi and HDL-c increased significantly (p-value for all < 0.05). Also, before and after adjustment based on baseline, the average changes indicated that the levels of insulin, HOMA-IR, TC, TG, LDL-c, SBP, DBP, MAP in the GSE group decreased more than in the control group (p for all < 0.05). Furthermore, the changes in HDL-c were significantly higher in the GSE group (p < 0.05). The between-groups analysis showed a significant decrease in the HOMA-β and AST before and after adjustment based on baseline levels (p < 0.05). Moreover, the changes in QUICKi after adjustment based on baseline levels were higher in the GSE group than in the control group. Also, between-groups analysis showed that the severity of hepatic steatosis was reduced in the intervention group compared to the placebo group (P = 0.002). CONCLUSIONS: It seems that GSE can be considered one of the appropriate strategies for controlling insulin resistance, hyperlipidemia, hypertension and hepatic steatosis in NAFLD patients. TRIAL REGISTRATION: The clinical trial was registered in the Iranian Clinical Trial Registration Center (IRCT20190731044392N1). https://irct.behdasht.gov.ir/trial/61413 . (The registration date:

Background: Despite rising non-alcoholic fatty liver disease (NAFLD) prevalence and its impact on liver health, there's a lack of studies on grape seed extract's (GSE) effect on oxidative stress and quality of life (QoL) in NAFLD patients. This study aims to fill this gap by the potential benefits of GSE in reducing oxidative stress and improving QoL. Methods: In this randomized clinical trial study, fifty patients with NAFLD were randomly assigned to receive either 2 tablets of GSE containing 250 mg of proanthocyanidins or placebo (25 participants in each group) for two months. QoL was evaluated using the SF-36 questionnaire, and oxidative stress variables (TAC, MDA, SOD, GPx, CAT, and IL-6) were measured at the beginning and end of the study. Results: Compared with the control group, the group supplemented with GSE experienced greater reductions in IL-6 and MDA (3.14±1.43 pg/ml vs. 2.80±0.31 pg/ml; 4.16±2.09 μM vs. 4.59±1.19 μM, p for all <0.05), as well as greater increases in TAC, SOD, and GPx levels (0.18±0.08 mM vs. -0.03±0.09 mM; 10.5±6.69 U/ml vs. 8.93±1.63 U/ml; 14.7±13.4 U/ml vs. 8.24±3.03 U/ml, p for all <0.05). Furthermore, the QoL questionnaire showed that physical limitations, general health, and total physical health were significantly improved in the GSE group compared with the placebo (17.0±42.0 vs. -12.0±37.5; 3.80±14.8 vs. -3.92±9.55; 5.08 5.26 vs. -7.01±13.7, p for all <0.05). Conclusions: GSE can be effective in improving oxidative stress and QoL in patients with NAFLD. More studies are needed to confirm the results of this study.

BACKGROUND: Imatinib is mainly metabolized by CYP3A4 and to a lesser extent by other isoenzymes, with N-desmethyl imatinib being its major equipotent metabolite. Being a CYP3A4 substrate, imatinib co-administration with CYP3A4 modulators would change its pharmacokinetic profile. The cancer chemoprevention potential and anticancer efficacy of many herbal products such as grape seed (GS) and green tea (GT) extracts had led to an increase in their concomitant use with anticancer agents. GS and GT extracts were demonstrated to be potent inhibitors of CYP3A4. The aim of this study is to investigate the effect of standardized GS and/or GT extracts at two different doses on the pharmacokinetics of imatinib and its metabolite, N-desmethyl imatinib, in SD-rats. METHODS: Standardized GS and/or GT extracts were administered orally once daily for 21 days, at low (l) and high (h) doses, 50 and 100 mg/kg, respectively, before the administration of a single intragastric dose of imatinib. Plasma samples were collected and analyzed for imatinib and N-desmethyl imatinib concentrations using LC-MS/MS method, then their non-compartmental pharmacokinetic parameters were determined. RESULTS: h-GS dose significantly decreased imatinib's Cmax and the [Formula: see text] by 61.1 and 72.2%, respectively. Similar effects on N-desmethyl imatinib's exposure were observed as well, in addition to a significant increase in its clearance by 3.7-fold. l-GT caused a significant decrease in imatinib's Cmax and [Formula: see text] by 53.6 and 63.5%, respectively, with more significant effects on N-desmethyl imatinib's exposure, which exhibited a significant decrease by 79.2 and 81.1%, respectively. h-GT showed similar effects as those of l-GT on the kinetics of imatinib and its metabolite. However, when these extracts were co-administered at low doses, no significant effects were shown on the pharmacokinetics of imatinib and its metabolite. Nevertheless, increasing the dose caused a significant decrease in Cmax of N-desmethyl imatinib by 71.5%. CONCLUSIONS: These results demonstrated that the pharmacokinetics of imatinib and N-desmethyl imatinib had been significantly affected by GS and/or GT extra

AIM: The objective of this research was to evaluate the antifungal properties of the association between grape seed and pea by using a nonpharmacological medical device that contains them. MATERIALS & METHODS: A murine model of vulvovaginal candidiasis, induced by Candida albicans infection, was used. RESULTS: We showed that topical treatment with the device significantly reduced the fungal burden in vagina and preserved vagina tissue architecture from C. albicans infection. CONCLUSION: We can support the potential beneficial effect of the association between grape and pea extract present in the medical device. Together these results supported this device as a favorable antifungal agent and a promising synergist with fluconazole in the clinical management of vulvovaginal candidiasis caused by C. albicans biofilms.

Breast cancer is the second most common cancer and the second leading cause of death from cancer among women in the United States (US). Cancer prevention and therapy through the use of phytochemicals that have epigenetic properties has gained considerable interest during the past few decades. Such dietary components include, but are not limited to, grape seed proanthocyanidins (GSPs) and resveratrol (Res), both of which are present in red wine. In this study, we report for the first time the synergistic effects of GSPs and Res on inhibiting MDA-MB-231 and MCF-7 human breast cancer cells. Our results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and clonogenic assays indicate that treatments with the combinations of GSPs and Res synergistically decreased cell viability and posttreatment cell proliferation in both cell lines. Additional analyses show that treatments with GSPs and Res in combination synergistically induced apoptosis in MDA-MB-231 cells by upregulating Bax expression and down-regulating Bcl-2 expression. DNA methyltransferase (DNMT) activity and histone deacetylase (HDAC) activity were greatly reduced in MDA-MB-231 and MCF-7 cells after treatments with GSPs and Res in combination. Collectively, our findings suggest that GSPs and Res synergistically inhibit human breast cancer cells through inducing apoptosis, as well as modulating DNA methylation and histone modifications.

CONTEXT: Endoplasmic reticulum (ER) stress in the liver is a pathological outcome of nutrient excess and is suggested to be one of the hits for progressive liver injury. OBJECTIVE: This study investigated whether grape seed proanthocyanidins (GSP) and metformin (MET) alone or in combination can relieve hepatic ER stress induced in rats subjected to calorie excess. MATERIAL AND METHODS: Male albino Wistar rats were given high calorie diet (HCD) for 45 days, while GSP (100 mg/kg body weight) and MET (50 mg/kg body weight) were administered either alone or in combination for last 15 days. RESULTS: GSP, MET or both had reduced the levels of ER stress markers and chaperons, and suppressed the activation of lipogenic and inflammatory mediators in rat liver. DISCUSSION: Though GSP and MET had reduced ER stress and inflammation individually, combination treatment with GSP + MET was more effective. CONCLUSION: We suggest intervention with GSP and MET intake has to be considered for the management of liver disorders.

The aim of this study was to investigate the synergistic antioxidant potential and protective effect of grape seed procyanidins (GSP) in combination with Auricularia auricular-judae polysaccharides (AAP IV) on radiation injury in splenocytes. Rat splenocyte irradiation resulted in significantly higher apoptosis rate, malondialdehyde (MDA) (p < 0.005), reactive oxygen species (ROS) (p < 0.01); cell viability, total superoxide dismutase (T-SOD) (p < 0.01), catalase (CAT) (p < 0.01), glutathione peroxidase (GSH-PX) (p < 0.05), activity and glutathione (GSH) (p < 0.01) levels were significantly reduced, compared with the control group. "GSP + AAP IV" treatment of rat splenocytes at doses of "GSP (0.3 μg/mL) + AAP IV (50 μg/mL)" displayed higher radioprotective and antioxidative effects than the administration of either GSP or AAP IV, as evident by lower levels of MDA (p < 0.001) concentration, as well as higher cell viability and T-SOD (p < 0.05), CAT (p < 0.005), GSH-PX (p < 0.01) and GSH content compared to the radiation group. In addition, in vivo studies have shown that "GSP + AAP IV" significantly ameliorated the decrease of spleen index (p < 0.005) and spleen GSH (p < 0.005) levels and significantly inhibited the increase of MDA (p < 0.005) levels of spleen with radiation-induced damage, compared with the non-treated group. The in vivo and in vitro results suggested that GSP and AAP IV have a synergistic protective effect against radiation-induced injury by improving the antioxidant and immunomodulation activities.

OBJECTIVE: Grape seed procyanidins (PC) are flavan-3-ol oligomers and polymers known for their biological activity in the gut. Grape seed extract (GSE) have been reported to reduce intestinal injury in a rat model of mucositis. We sought to investigate effects of purified PC fractions differing in mean degree of polymerization (mDP) combined with 5-Fluorouracil (5-FU) chemotherapy on the viability of colon cancer cells (Caco-2). DESIGN: SixPC fractions (F1-F6) were isolated from Cabernet Sauvignon seeds at two ripeness stages: pre-veraison unripe (immature) and ripe (mature), utilizing step gradient, low-pressure chromatography on a Sephadex LH-20 resin. Fractions were tested on Caco-2 cells, alone and in combination with 5-FU. Eluted fractions were characterized by phloroglucinolysis and gel permeation chromatography. Cell viability was determined by the 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) (MTT) assay. RESULTS: All isolated fractions significantly reduced Caco-2 cell viability compared to the control (P<0.05), but F2 and F3 (mDP 2-6) were the most active fractions (immature F2 = 32% mDP 2.4, F3 = 35% mDP 5.8 and mature F2 = 13% mDP 3.6 and F3 = 17% mDP 5.9; percentage of viable cells remaining) on Caco-2 cells. When combined with 5-FU, immature fractions F1-F3 enhanced the cell toxicity effects of 5-FU by 27-73% (P<0.05). Mature seed PC fractions (F1-F4) significantly enhanced the toxicity of 5-FU by 60-83% against Caco-2 cells (P<0.05). Moreover, some fractions alone were more potent at decreasing viability in Caco-2 cells (P<0.05; immature fractions = 65-68% and mature fractions = 83-87%) compared to 5-FU alone (37%). CONCLUSIONS: PCs of mDP 2-6 (immature F1-F3 and mature F1 and F4)not only enhanced the impact of 5-FU in killing Caco-2 cells, but also surpassed standard 5-FU chemotherapy as an anti-cancer agent.The bioactivity of PC is therefore attributed primarily to lower molecular weight PCs.

PURPOSE: Grape seed extract (GSE) has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. To determine the clinical effect of GSE on CYP2D6, the pharmacokinetic interaction between GSE and the sensitive CYP2D6 probe dextromethorphan in healthy adult volunteers was examined. METHODS: In this open label, randomized, cross-over study, 30 subjects were assigned to cohort A or B. Both cohorts ingested 30 mg dextromethorphan hydrobromide on day 1 and day 10. Cohort A received 100 mg GSE capsules three times daily on days 8, 9 and 10, while cohort B started with GSE on day -1 until day 1. After urine collection (0-8 h) on day 1 and day 10, the urinary dextromethorphan to dextrorphan metabolic ratio was determined. RESULTS: Among 28 evaluable subjects, an increase of the urinary metabolic ratio was observed in 16 subjects (57 %). The mean metabolic ratio (± standard deviation) before and after GSE supplementation was 0.41 (± 0.56) and 0.48 (± 0.59), respectively. This result was neither statistically (P = 0.342) nor clinically [geometric mean ratio 1.10, 90 % CI (0.93-1.30)] significant. Further, the majority (73 %) of the included subjects did not experience any adverse events after intake of dextromethorphan or GSE. CONCLUSIONS: Supplementation of GSE did not significantly affect the urinary dextromethorphan to dextrorphan metabolic ratio in healthy volunteers. The results of this clinical study indicate that GSE appears to be safe to combine with drugs extensively metabolized by CYP2D6, such as dextromethorphan and tamoxifen.

16. Eur J Clin Pharmacol. 2013 Nov;69(11):1883-90. doi: 10.1007/s00228-013-1558-9. Epub 2013 Jul 24. The effect of grape seed extract on the pharmacokinetics of dextromethorphan in healthy volunteers. Goey AK(1), Meijerman I, Beijnen JH, Schellens JH. Author information: (1)Department of Pharma

Formyl peptide receptor 1 (FPR1) plays an important role in the rapid progression of glioblastoma and has been considered as a molecular target for the treatment. Previously, we have shown that oligomer proanthocyanidins (F2, degree of polymerization 2-15), isolated from grape seeds, inhibited FPR1-mediated chemotaxis of U-87 glioblastoma cells. In the present study, we investigated the capacity of F2 to interact with FPR1. The cross attenuation of chemotaxis revealed that F2 shared FPR1 with formyl-methionyl-leucyl-phenylalanine (fMLF), which is a prototype agonist of FPR1. F2 was chemotactic for U-87 cells, and the chemotactic response was abolished when FPR1 gene was silenced or FPR1 was competitively occupied. We further show that F2 specifically blocked the binding of fluorescent agonist to FPR1. Interestingly, F2 exhibited the characteristic of a partial agonist for FPR1, as shown by its capacity to activate FPR1-mediated PI3K-PKC-MAPK pathways. Meanwhile, F2 also attenuated fMLF-triggered MAPK activation, suggesting that F2 could antagonize the effect of an agonist. Furthermore, F2 abolished the invasion of U-87 cells induced by fMLF. Thus, we have identified F2 as a novel, partial agonist for FPR1, which may be useful for glioblastoma therapy.

Indomethacin (IND) is a non-steroid anti-inflammatory agent that is known to induce severe gastric mucosal lesions. In this study, we investigated the protective effect of selenium (SEL), grape seed extract (GSE), and both on IND-induced gastric mucosal ulcers in rats. Sprague-Dawley rats (200-250 g) were given SEL, GSE, and both by oral gavage for 28 days, and then gastric ulcers were induced by oral administration of 25 mg/kg IND. Malondialdehyde (MDA), non-enzymatic (reduced glutathione, GSH) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidants, prostaglandin E2 (PGE2) in gastric mucosa, and serum tumor necrosis factor alpha (TNF-α) were measured. Moreover, gastric ulcer index and preventive index were determined. Indomethacin increased the gastric ulcer index, MDA, TNF-α, and decreased PGE2 and non-enzymatic (GSH) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidants. Pretreatment with SEL, GSE, and both significantly decreased the gastric ulcer index, MDA, and TNF and increased antioxidants and PGE2. Histopathological observations confirm the gastric ulcer index and biochemical parameters. Selenium and GSE have a protective effect against IND-induced gastric ulcers through prevention of lipid peroxidation, increase of GSH, activation of radical scavenging enzymes, PGE2 generation, and anti-inflammatory activity. Co-administration of GSE and SEL is more effective than GSE or SEL alone.

INTRODUCTION AND AIMS: Achieving durable adhesion of composite-resins to dentin remains a key challenge in restorative dentistry, highlighting the need for biomodification strategies. Therefore, this umbrella review aims to systematically overview dentin biomodifiers and evaluate their influence on the durability of composite-resin restorations. METHODS: Literature search was conducted in PubMed, Scopus, and Web of Science up to October 2024, focusing on three concepts: dentin, biomodification, and bond strength (PROSPERO: CRD42024588804). The corrected covered area (CCA) was calculated to evaluate overlap among the included systematic reviews (SRs). RESULTS: Among 486 identified papers, 9 SRs were selected including 7 meta-analyses. Twenty biomodification agents were identified and classified into natural, physical and chemical agents. These agents were assessed in 51 different setups with micro-tensile bond strength used in 68.62% of them. Timing of bond strength assessments varied from immediate to a 36-months period. As natural agents, Grape Seed Extract and chitosan improved bond strength after long-term aging, while induced riboflavin improved the short and medium-term periods only. Among all categories, the most studied biomodifier was Non-Thermal Atmospheric Plasma, a physical agent, which consistently enhanced resin-dentin bonding over time. However, chemical approaches did not show promising bond strength results at some exceptions. Sodium hypochlorite (NaOCl) and hypochlorous acid both immediately decreased bond strength. Overlap among reviews was slight (CCA = 1.52 %). CONCLUSION: Various biomodifiers show promise for enhancing adhesion and durability of composite-resin restorations, with their combinations potentially offering synergistic effects. CLINICAL RELEVANCE: Systematically identifying and characterizing dentin biomodifiers within their limitations lays the groundwork for evidence-based frameworks that guide dentists and shape future research. At present, physical scrubbing and air abrasion are the only readily available dentin biomodification techniques. Riboflavin and chitosan show promise as effective natural and affordable agents; howeve

A promising approach for managing root caries is the use of cross-linking agents to stabilize collagen. However, despite testing various natural and synthetic agents in vitro, their efficacy remains uncertain. The aim of this review was to examine which cross-linking agent performs better in reducing root caries lesion depth and the release of hydroxyproline, which is a marker of collagen degradation. Studies evaluating the impact of cross-linking agents on dentin were included, while studies performed on enamel surface/cell cultures and studies evaluating collagenase inhibitors were excluded, among others. A comprehensive search covered eight databases, and study quality was assessed using the QUINN Tool for in vitro dental studies. Synthesis of the results was done using a Bayesian network meta-analysis to compare agents. Fifty studies involving 31 cross-linking agents were included for qualitative synthesis. The network meta-analysis for lesion depth involved 284 samples across 36 comparisons and ranked cross-linking agents in terms of their caries lesion depth-reducing effect (from best to worst): naringin > quercetin > riboflavin > proanthocyanidins > hesperidin > glutaraldehyde > cranberry > grape seed extract > untreated controls. Only naringin, quercetin, proanthocyanidins, and glutaraldehyde showed statistically significant efficacy over untreated controls. Cranberry extract excelled in reducing hydroxyproline release, followed by proanthocyanidins. In conclusion, proanthocyanidins positively affected both outcomes, suggesting they are prime candidates for translational research. Clinical studies are now essential to evaluate their real-world effectiveness against root caries. PROSPERO-CRD42023404911. © 2024 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.

OBJECTIVE: To provide an overview of the available scientific evidence from in vitro studies regarding the effect induced by the flavonoids contained in grape seed extracts (GSE) and cranberry on the microbiological activity of Streptococcus mutans (S. mutans). METHODS: This systematic review was performed following the parameters of the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Electronic and manual searches were conducted using PubMed, ScienceDirect, Web of Science, EBSCO, and Cochrane databases. Reference lists of selected articles were reviewed to identify relevant studies. The search was not limited by year and was conducted solely in English. Eligible studies comprised publications describing in vitro studies that evaluated the effect of flavonoids derived from GSE and cranberry extracts on the microbiological activity of S. mutans. Common variables were identified to consolidate the data. Authors of this review independently screened search results, extracted data, and assessed the risk of bias. RESULTS: Of the 420 studies identified from the different databases, 22 publications were finally selected for review. The risk of bias was low in 13 articles and moderate in 9. The studies analyzed in this review revealed that cranberry extract has an inhibitory effect on the bacterial growth of S. mutans in ranges from 0.5 mg/mL to 25 mg/mL, and GSE exerts a similar effect from 0.5 mg/mL to 250 mg/mL. Additionally, the extracts or their fractions showed reduced biofilm formation capacity, decreased polymicrobial biofilm biomass, deregulation of glycosyltransferases (Gtf) B and C expression, and buffering of pH drop. In addition to adequate antioxidant activity related to polyphenol content. CONCLUSIONS: The overall results showed that the extracts of cranberry and grape seed were effective in reducing the virulence factors of the oral pathogen. According to the data, proanthocyanidins are the active components in cranberry and grape seed that effectively resist S. mutans. They can inhibit the formation of insoluble polysaccharides in the extracellular matrix and prevent glycan-mediated adhesion, cohesion, and aggregat

INTRODUCTION: There is a growing interest in the considerable benefits of grape products intake, as some studies have indicated that they may improve cardiometabolic risk factors. However, the widespread impact of grape products on the anthropometric indices is not fully resolved. METHOD: The purpose of this systematic review and meta-analysis was to examine the effects of grape products intake on anthropometric indices in adults. Randomized controlled trials (RCT) examining the effects of grape products intake on anthropometric indices, published up to December 2021, were identified through PubMed, SCOPUS, and ISI Web of Science databases. 30 studies with 35 effect sizes, including 1284 participants (708 cases and 576 controls), were included and analyzed using a random-effects model to calculate weighted mean differences (WMDs) with 95% confidence interval (CI). RESULT: The outcomes have revealed grape products intake to significantly decrease body weight (p = 0.001) and body mass index (p = 0.004) in obese participants, and also, a greater effect was observed when grape seed extract was used. CONCLUSION: Our study suggests that grape products intake may help to decrease body weight in obese participants. Future large RCTs with longer duration and obese populations are needed to expand our findings.

CONTEXT: Anticariogenic properties have been ascribed to polyphenolic compounds present in high concentrations in numerous fruits. Berries, in particular, have been reported as potentially having an inhibitory effect on the dental biofilm and subsequently on caries, but the evidence is unclear. OBJECTIVE: The objective of this review was to explore the literature and summarize the evidence for berries having an inhibitory effect on the dental biofilm and an anticariogenic effect. DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, the PubMed, Web of Science, and SCOPUS databases were scanned using predefined and accessible terms, with a search strategy based on a structured PICO question. DATA EXTRACTION: After article selection, 23 studies met the inclusion criteria, most of them being in vitro studies. A risk assessment was performed, and data were extracted and presented in a table for qualitative analysis. DATA ANALYSIS: Meta-analyses were conducted using standardized mean differences (SMDs) with a 95% confidence interval (CI) by Review manager 5.4. RESULTS: Only 3 types of berries were found to have a reported anticaries effect: grape seed extract (GSE), cranberry, and sour cherry. Nine studies that fulfilled the eligibility criteria were subjected to quantitative analysis. Meta-analyses showed GSE was associated with enhanced remineralization of dental enamel (SMD = .96 95% CI [.45, 1.46], P < .0002) and of dentin (SMD = .65 95% CI [.13, 1.17], P = .01). Cranberry extracts positively influenced the cariogenic dental biofilm by decreasing the biofilm biomass (SMD = -2.23 95% CI [-4.40, -.05], P = .04), and biovolume (SMD = -2.86 95% CI [-4.34, -1.37], P = .0002), and increasing the biofilm pH (SMD = 7.9 95% CI [3.49, 12.31], P < .0004). CONCLUSION: Within the limitations of this systematic review and metaanalysis, GSE and cranberries or their active compounds could represent an alternative for caries management. Further clinical trials are needed to verify this effect in a clinical setting. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020223579. © The Author(s) 2023. Published by

The favorable influence of grape consumption on metabolic diseases has previously been shown in studies. We sought to assess the effects of grape intake on liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), in adults. We performed literature search in online databases, to find eligible randomized controlled trials (RCTs). we considered RCTs that met the following criteria: RCTs consisted of use of grape products on ALT, AST, and ALP in adults (≥18 years) with at least 2 weeks intervention duration. Pooling data from 11 trials showed that grape products intake significantly reduced ALP (p = .010), without any significant changes in ALT (p = .234) and AST (p = .300). In subgroup analysis, we found a significant reduction in ALP, ALT, and AST when the duration of intervention was ≥12 weeks, and when grape seed extract (GSE) was administered. The variable duration and dosage of intervention was one of the sources of bias in our meta-analysis. Additionally, participants involved in included studies had different physiological status and various age groups. Grape products administration may significantly improve ALT, AST, and ALP in adults in long-term interventions and/or when GSE is administered. It should be noted that the favorable effects of grape consumption were small and may not reach clinical importance. © 2022 John Wiley & Sons Ltd.