Grape seed extract prevents oestrogen deficiency-induced bone loss by modulating the gut microbiota and metabolites.

Proanthocyanidin-rich grape seed extract (GSE) has been shown to have the potential to protect bones, although the underlying mechanism remains unknown. The current study aims to explore GSE's preventive and therapeutic impact on bone loss induced by oestrogen deficiency and the underlying mechanism through the gut microbiota (GM) and metabolomic responses. In oestrogen-deficient ovariectomized (OVX) mice, GSE ameliorated bone loss by inhibiting the expansion of bone marrow adipose tissue (BMAT), restoring BMAT lipolysis and promoting bone formation. GSE regulated OVX-induced GM dysbiosis by reducing the abundance of opportunistic pathogenic bacteria, such as Alistipes, Turicibacter and Romboutsia, while elevating the abundance of beneficial bacteria, such as Bifidobacterium. The modified GM primarily impacted lipid and amino acid metabolism. Furthermore, the serum metabolites of GSE exhibited a significant enrichment in lipid metabolism. In summary, GSE shows potential as a functional food for preventing oestrogen deficiency-induced bone loss by modulating GM and metabolite-mediated lipid metabolism.

Dietary supplementation with grape seed extract from Vitus vinifera prevents suppression of GABAergic protein expression in female Sprague Dawley trigeminal ganglion in a model of chronic temporomandibular joint disorder.

OBJECTIVE: To investigate cellular changes in protein expression in the trigeminal ganglion in an established preclinical chronic model of temporomandibular joint disorder (TMD) in response to grape seed extract (GSE) supplementation based on its beneficial use in preclinical chronic orofacial pain models. DESIGN: Three experimental conditions included female Sprague-Dawley rats as naïve controls, and animals subjected to neck muscle inflammation and prolonged jaw opening with and without daily supplementation of GSE in the drinking water prior to inflammation. Changes were evaluated in mechanical sensitivity to von Frey filaments and protein expression in the trigeminal ganglion of animals 14 days post jaw opening. RESULTS: Calcitonin-gene related peptide and protein kinase A, proteins positively associated with peripheral sensitization and enhanced nociception, did not show elevated expression at day 14 in the model compared to naïve or GSE supplemented animals. However, neuronal levels of glutamate decarboxylase (GAD) 65/67, which are enzymes responsible for the synthesis of the inhibitory neurotransmitter GABA that functions to suppress neuronal excitability, were significantly decreased on day 14 post jaw opening. Similarly, a significant decrease in neuronal expression of the GABA receptor subunits GABAB1 and GABAB2, but not GABAA, was observed in the TMD model. Importantly, GSE prevented suppression of GAD 65/67 and GABAB subunits, maintaining levels similar to naïve animals. CONCLUSION: Results from our study provide evidence of the downregulation of inhibitory GABAergic proteins in trigeminal ganglion neurons in a preclinical chronic TMD model and the benefits of GSE supplementation in preventing their suppression and maintaining normal levels.

Effect of flavonoids from grape seed and cranberry extracts on the microbiological activity of Streptococcus mutans: a systematic review of in vitro studies.

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 aggregation of the proteins in S. mutans. This suggests that these natural extracts could play an important role in the prevention of cariogenic bacterial colonization, as well as induce a decrease in their microbiological activity.

Grape seed-derived procyanidins decreases neuropathic pain and nerve regeneration by suppression of toll-like receptor 4-myeloid differentiation factor-88 signaling.

Background: Recent studies have shown that peripheral nerve regeneration process is closely related to neuropathic pain. Toll-like receptor 4 (TLR4) signaling was involved in different types of pain and nerve regeneration. TLR4 induced the recruitment of myeloid differentiation factor-88 adaptor protein (MyD88) and NF-κB-depended transcriptional process in sensory neurons and glial cells, which produced multiple cytokines and promoted the induction and persistence of pain. Our study aimed to investigate procyanidins's effect on pain and nerve regeneration via TLR4-Myd88 signaling. Methods: Spinal nerve ligation (SNL) model was established to measure the analgesic effect of procyanidins. Anatomical measurement of peripheral nerve regeneration was measured by microscopy and growth associated protein 43 (GAP43) staining. Western blotting and/or immunofluorescent staining were utilized to detect TLR4, myeloid differentiation factor-88 adaptor protein (MyD88), ionized calcium-binding adapter molecule 1 (IBA1) and nuclear factor kappa-B-p65 (NF-κB-p65) expression, as well as the activation of astrocyte and microglia. The antagonist of TLR4 (LPS-RS-Ultra, LRU) were intrathecally administrated to assess the behavioral effects of blocking TLR4 signaling on pain and nerve regeneration. Result: Procyanidins reduced mechanical allodynia, thermal hyperalgesia and significantly suppressed the number of nerve fibers regenerated and the degree of myelination in SNL model. Compared with sham group, TLR4, MyD88, IBA1 and phosphorylation of NF-κB-p65 were upregulated in SNL rats which were reversed by procyanidins administration. Additionally, procyanidins also suppressed activation of spinal astrocytes and glial cells. Conclusion: Suppression of TLR4-MyD88 signaling contributes to the alleviation of neuropathic pain and reduction of nerve regeneration by procyanidins.

Slightly viscous dispersions of mucoadhesive polymers as vehicles for nasal administration of dopamine and grape seed extract-loaded solid lipid nanoparticles.

With the aim to find an alternative vehicle to the most used thermosensitive hydrogels for efficient nanotechnology-based nose-to-brain delivery approach for Parkinson's disease (PD) treatment, in this work we evaluated the Dopamine (DA) and the antioxidant grape seed-derived pro-anthocyanidins (Grape Seed Extract, GSE) co-loaded solid lipid nanoparticles (SLNs) put in slight viscous dispersions (SVDs). These SVDs were prepared by dispersion in water at low concentrations of mucoadhesive polymers to which SLN pellets were added. For the purpose, we investigated two polymeric blends, namely Poloxamer/Carbopol (PF-127/Carb) and oxidized alginate/Hydroxypropylmethyl cellulose (AlgOX/HPMC). Rheological studies showed that the two fluids possess Newtonian behaviour with a viscosity slightly higher that water. The pH values of the SVDs were mainly within the normal range of nasal fluid as well as almost no osmotic effect was associated to both SVDs. All the SVDs were capable to provide DA permeation through nasal porcine mucosa. Moreover, it was found that PF-127/Carb blend possesses penetration enhancer capability better than the Alg OX/HPMC combination. Flow cytometry studies demonstrated the uptake of viscous liquids incorporating fluorescent SLNs by human nasal RPMI 2650 cell in time-dependent manner. In conclusion, the SVD formulations may be considered promising alternatives to thermosensitive hydrogels strategy. Moreover, in a broader perspective, such SVD formulations may be also hopeful for treating various neurological diseases beyond PD treatment.

The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

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-ß 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: 30/03/2022).

Dopamine- and Grape-Seed-Extract-Loaded Solid Lipid Nanoparticles: Interaction Studies between Particles and Differentiated SH-SY5Y Neuronal Cell Model of Parkinson's Disease.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, primarily associated with dopaminergic neuron depletion in the Substantia Nigra. Current treatment focuses on compensating for dopamine (DA) deficiency, but the blood-brain barrier (BBB) poses challenges for effective drug delivery. Using differentiated SH-SY5Y cells, we investigated the co-administration of DA and the antioxidant Grape Seed Extract (GSE) to study the cytobiocompability, the cytoprotection against the neurotoxin Rotenone, and their antioxidant effects. For this purpose, two solid lipid nanoparticle (SLN) formulations, DA-co-GSE-SLNs and GSE-ads-DA-SLNs, were synthesized. Such SLNs showed mean particle sizes in the range of 187-297 nm, zeta potential values in the range of -4.1--9.7 mV, and DA association efficiencies ranging from 35 to 82%, according to the formulation examined. The results showed that DA/GSE-SLNs did not alter cell viability and had a cytoprotective effect against Rotenone-induced toxicity and oxidative stress. In addition, this study also focused on the evaluation of Alpha-synuclein (aS) levels; SLNs showed the potential to modulate the Rotenone-mediated increase in aS levels. In conclusion, our study investigated the potential of SLNs as a delivery system for addressing PD, also representing a promising approach for enhanced delivery of pharmaceutical and antioxidant molecules across the BBB.

Improved analysis of grape seed extract by liquid chromatography-high resolution mass spectrometry (LC-HRMS) reveals that proanthocyanidin-protein interaction mechanisms in cream depend on degree of polymerization.

This study aimed to comprehensively characterize chemical profiles of proanthocyanidins (PACs) from grape seed extract (GSE), examine their interactions with proteins in a cream system, and define the mechanisms mediating PAC-protein interactions. GSE PACs were fractionated and characterized by thiolysis followed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis. New PACs with a degree of polymerization (DP) up to 16 were identified by improved HRMS data processing methods. In the model cream system, high-DP PACs exhibited greater precipitation capacity and protein binding than low-DP PACs. Low-DP PACs primarily engaged in hydrogen bonding, while high-DP PACs predominantly utilized multiple hydrophobic interaction sites to form cream protein aggregates. Furthermore, particle size and viscosity measurement of cream revealed a progressively DP-dependent increase in aggregated fat globules and cream viscosity. These findings enhanced our understanding of PACs' structural intricacies and highlighted their functional role as PAC-rich natural ingredients in creating structured cream systems.

Grape seed proanthocyanidin extract promotes skeletal muscle fiber type transformation through modulation of cecal microbiota and enhanced butyric acid production.

The conversion of fast-twitch fibers into slow-twitch fibers within skeletal muscle plays a crucial role in improving physical stamina and safeguarding against metabolic disorders in individuals. Grape seed proanthocyanidin extract (GSPE) possesses numerous pharmacological and health advantages, effectively inhibiting the onset of chronic illnesses. However, there is a lack of research on the specific mechanisms by which GSPE influences muscle physiology and gut microbiota. This study aims to investigate the role of gut microbiota and their metabolites in GSPE regulation of skeletal muscle fiber type conversion. In this experiment, 54 male BALB/c mice were randomly divided into three groups: basal diet, basal diet supplemented with GSPE, and basal diet supplemented with GSPE and antibiotics. During the feeding period, glucose tolerance and forced swimming tests were performed. After euthanasia, samples of muscle and feces were collected for analysis. The results showed that GSPE increased the muscle mass and anti-fatigue capacity of the mice, as well as the expression of slow-twitch fibers. However, the beneficial effects of GSPE on skeletal muscle fibers disappeared after adding antibiotics to eliminate intestinal microorganisms, suggesting that GSPE may play a role by regulating intestinal microbial structure. In addition, GSPE increased the relative abundance of Blautia, Muribaculaceae, and Enterorhabdus, as well as butyrate production. Importantly, these gut microbes exhibited a significant positive correlation with the expression of slow-twitch muscle fibers. In conclusion, supplementation with GSPE can increase the levels of slow-twitch fibers by modulating the gut microbiota, consequently prolonging the duration of exercise before exhaustion. PRACTICAL APPLICATION: This research suggests that grape seed proanthocyanidin extract (GSPE) has potential applications in improving physical stamina and preventing metabolic disorders. By influencing the gut microbiota and increasing butyric acid production, GSPE contributes to the conversion of fast-twitch muscle fibers into slow-twitch fibers, thereby enhancing anti-fatigue capacity and exercise endurance. While further studies are needed, incorporating GSPE into dietary supplements or functional foods could support individuals seeking to optimize their exercise performance and overall metabolic health.

Effects of dietary supplementation of grape seed extract in comparison with excessive level of vitamin E on growth performance and antioxidant function of broilers.

The present study was carried out to evaluate the effects of dietary vitamin E (VE) or grape seed extract (GSE) on the growth performance and antioxidant function of broilers. Two hundred sixteen broiler chicks were randomly assigned to 3 diets: diet supplemented with oxidized rice bran oil (CN group), CN group with 25 mg/kg VE or 100 mg/kg GSE. Dietary VE or GSE improved the growth performance, reverted the disturbed levels of liver antioxidant enzymes, and reduced liver damage of broilers fed oxidized rice bran oil. The mRNA data showed that supplementation of VE or GSE enhanced the antioxidant capacity of the broiler liver through activation of the Keap1-Nrf2/ARE signaling pathway. The results suggested that VE and GSE can increase weight gain, improve the oxidative status, and alleviate liver injury in broiler chicken fed oxidized rice bran oil.

Ultrasonic-assisted extraction of grape seed procyanidins, preparation of liposomes, and evaluation of their antioxidant capacity.

The residue remaining after oil extraction from grape seed contain abundant procyanidins. An ultrasonic-assisted enzyme method was performed to achieve a high extraction efficiency of procyanidins when the optimal extraction conditions were 8 U/g of cellulase, ultrasound power of 200 W, ultrasonic temperature of 50 ℃, and ultrasonic reaction time of 40 min. The effects of free procyanidins on both radical scavenging activity and thermal stability at 40, 60, and 80 ℃ of the procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were discussed. The presence of procyanidins at concentrations ranging from 0.02 to 0.10 mg/mL was observed to be effective at inhibiting lipid oxidation by 15.15 % to 69.70 % in a linoleic acid model system during reaction for 168 h, as measured using the ferric thiocyanate method. The procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were characterized by measuring the mean particle size and encapsulation efficiency. Moreover, the holographic plots showed that the effect-response points of procyanidins combined with α-tocopherol in liposomes were lower than the addition line and 95 % confidence interval limits. At the same time, there were significant differences between the theoretical IC50add value and the experimental IC50mix value. The interaction index (γ) of all combinations was observed to be less than 1. These results indicated that there was a synergistic antioxidant effect between procyanidins combined with α-tocopherol, which will show promising prospects in practical applications. In addition, particle size differentiation and morphology agglomeration were observed at different time points of antioxidant activity determination (0, 48, 96 h).

Effects of grape seed procyanidins on the lipid metabolism of growing-finishing pigs based on transcriptomics and metabolomics analyses.

This study investigated how lipid metabolism in the longissimus thoracis is influenced by the diet supplemented with grape seed procyanidins (GSPs) in growing-finishing pigs. Forty-eight crossbred pigs were randomly assigned to four groups, each receiving a basal diet, or basal diet added with 150, 200, and 250 mg/kg GSPs. Transcriptomics and metabolomics were employed to explore differential gene and metabolite regulation. The expression of key lipid metabolism-related genes was tested via qRT-PCR, and the lipid and fatty acid composition of the longissimus thoracis were determined. Dietary GSPs at different concentrations upregulated lipoprotein lipase (LPL), which is involved in lipolysis, and significantly increased the mRNA expression levels of carnitine palmitoyltransferase-1B (CPT1B) and cluster of differentiation 36 (CD36), implicated in transmembrane transport of fatty acids. Dietary supplementation of GSPs at 200 or 250 mg/kg markedly reduced total cholesterol and triglyceride content in longissimus thoracis. Dietary GSPs significantly decreased the contents of low-density lipoprotein cholesterol and saturated fatty acids, while increasing unsaturated fatty acids. In conclusion, GSPs may regulate lipid metabolism, reducing cholesterol level, and improving fatty acid composition in the longissimus thoracis of growing-finishing pigs. Our findings provide evidence for the beneficial effects of GSPs as pig feed additives for improving lipid composition.

Bioaccessibility and Antioxidant Capacity of Grape Seed and Grape Skin Phenolic Compounds After Simulated In Vitro Gastrointestinal Digestion.

Grapes present recognized beneficial effects on human health due to their polyphenolic composition. The grape overproduction together with the wine sales down and the world socioeconomic situation makes the wine grape valorization a promising strategy to give an added-value to this natural product. The objective of the present work was to study the influence of in vitro gastrointestinal digestion on antioxidant capacity and polyphenolic profile of skin and seed extracts of different grape varieties (Tempranillo, Graciano, Maturana tinta and Hondarrabi zuri). After in vitro gastrointestinal digestion, total phenolic content (TPC) of seed polyphenolic extracts decreased significantly for all the varieties. The highest decrease was for Tempranillo going from 108 ± 9 to 50 ± 3 mg / g dry matter (dm). This variety also showed the highest decrease of 90% in antioxidant capacity. However, for all the skin polyphenolic extracts there was an increase in TPC. The highest variation was also for Tempranillo. It varied from 10.1 ± 0.8 to 55.1 ± 0.9 mg / g dm. Among red varieties Tempranillo skin polyphenolic extract showed the lowest undigested anthocyanin content but the highest bioaccessibility index (BI) of 77%. For flavanols, flavonols and procyanidins the seed polyphenolic extracts showed a BI at the intestinal phase between 11% for (+)-epicatechin gallate to 130% procyanidin A2. The results of this study suggest that grape skin extracts and grape seed extracts are a reliable source of bioaccessible antioxidant polyphenols, to be used for the development of antioxidant supplements with specific functionalities depending on the grape variety.

Grape seed extract supplementation in non-alcoholic fatty liver disease.

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.

Grape seed extract prevents chlorpyrifos-induced toxicity in rat liver through the modulation of phase I detoxification pathway.

Chlorpyrifos (CPF) poisoning is a public health problem for which there is not currently any effective prophylaxis. In this study, we investigated the protective effect of grape seed extract (GSE) against CPF-induced hepatotoxicity. Rats were daily treated either with CPF (2 mg/kg) or CPF and GSE (20 mg/kg) for 1 week, sacrificed, and their livers dissected for biochemical, molecular, and histopathological analyses. CPF generated liver dysfunction by altering carbohydrate, lipid, amino acid, ammonia and urea metabolism, and provoked mitochondrial impairment through disturbing tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and mitochondrial viability. CPF also induced cholinergic excitotoxicity along with oxidative stress and histopathological alterations. Interestingly, treatment with GSE prevented all the detrimental effects of CPF through the regulation of cytochrome P450 (CYP450) gene expression. Molecular docking analysis indicated that GSE-containing polyphenols acted as epigenetic modulators through inhibiting DNA (cytosine-5)-methyltransferase 1 (DNMT1), thus favoring the CYP2C6 detoxification pathway. Thereby, GSE might be a promising strategy in the protection of the liver against CPF toxicity.

Dietary short-term supplementation of grape seed proanthocyanidin extract improves pork quality and promotes skeletal muscle fiber type conversion in finishing pigs.

Plant extracts are commonly used as feed additives to improve pork quality. However, due to their high cost, shortening the duration of supplement use can help reduce production costs. In this study, we aimed to investigate the effects of grape seed proanthocyanidin extract (GSPE) on meat quality and muscle fiber characteristics of finishing pigs during the late stage of fattening, which was 30 days in our experimental design. The results indicated that short-term dietary supplementation of GSPE significantly reduced backfat thickness, but increased loin eye area and improved meat color and tenderness. Moreover, GSPE increased slow myosin heavy chain (MyHC) expression and malate dehydrogenase (MDH) activity, while decreasing fast MyHC expression and lactate dehydrogenase (LDH) activity in the Longissimus thoracis (LT) muscle. Additionally, GSPE increased the expression of Sirt1 and PGC-1α proteins in the LT muscle of finishing pigs and upregulated AMP-activated protein kinase α 1 (AMPKα1), AMPKα2, nuclear respiratory factor 1 (NRF1), and calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß) mRNA expression levels. These findings suggest that even during the late stage of fattening, GSPE treatment can regulate skeletal muscle fiber type transformation through the AMPK signaling pathway, thereby affecting the muscle quality of finishing pigs. Therefore, by incorporating GSPE into the diet of pigs during the late stage of fattening, producers can enhance pork quality while reducing production costs.

Grape seed proanthocyanidin extract alleviates inflammation in experimental colitis mice by inhibiting NF-κB signaling pathway.

Ulcerative colitis (UC) is a complex inflammatory disease of colorectum that induces abnormal immune responses and severely affects the quality of life of the patients. Grape seed proanthocyanidin extract (GSPE) exerts anti-inflammatory and antioxidant functions in many inflammatory diseases. The objective of this study was to investigate the potential therapeutic effects and underlying mechanisms of GSPE in UC using a dextran sodium sulfate (DSS)-induced mouse UC model and a lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model. In this study, we found that the GSPE markedly prevented DSS-induced weight loss and colon length shortening in UC mice. Further investigations showed that GSPE significantly attenuated the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß, and elevated the expression of anti-inflammatory cytokine IL-10 in the colon tissues and serum of DSS-induced colitis mice by suppressing NF-κB signaling pathway. Furthermore, LPS-induced inflammation in RAW264.7 cells was also reversed by GSPE. Taken together, our results confirm that GSPE can ameliorate inflammatory response in experimental colitis via inhibiting NF-κB signaling pathway. This study advances the research progress on a potentially effective therapeutic strategy for inflammatory bowel diseases.

Antibacterial effect of red laser-activated silver nanoparticles synthesized with grape seed extract against Staphylococcus aureus and Escherichia coli.

Living organisms, particularly humans, frequently encounter microorganisms such as bacteria, fungi, and viruses in their surroundings. Silver nanoparticles are widely used in biomedical devices because of their antibacterial and antiviral properties. The study evaluates the efficacy of red laser and silver nanoparticles from grape seed extract (AgNPs-GSE) in reducing Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria, which cause infections. The sample comprised three groups: a control group without laser irradiation (T0), Escherichia coli samples (A1 and A2) irradiated with a 405-nm diode laser at different times and concentrations of silver nanoparticles, and Staphylococcus aureus samples (A3 and A4) illuminated with a 405-nm diode laser at different times and concentrations. Bacteria in groups A2 and A4 were treated with a photosensitizer (PS) made from grape seed extracts, incubated for 10 min, and then irradiated for 90, 120, 150, and 180 s. The samples were cultured on TSA media, set at 37 °C, counted using a Quebec colony counter, and analyzed using ANOVA and Tukey tests with a significance level of p < 0.05. The study illustrated that the combination of 10 µl of AgNPs-GSE, exposure to a red laser at 405 nm, and an energy density of 3.44 J/cm2 effectively photoinactivated both Escherichia coli and Staphylococcus aureus bacteria. For Escherichia coli bacteria irradiated for 180 s with concentrations of 1 mM, 1.5 mM, and 2 mM AgNPs-GSE, bacterial viability decreased by 64.50%, 70.74%, and 79.53%, respectively. Similarly, Staphylococcus aureus bacteria, subjected to irradiation for 180 s with concentrations of 1 mM, 1.5 mM, and 2 mM AgNPs-GSE, demonstrated reductions in bacterial viability by 70.23%, 73.47%, and 85.04%, respectively. The findings from the present study indicate that at an energy density of 3.44 J/cm2, it was possible to inactivate Escherichia coli by 79.53% and Staphylococcus aureus by 85.04%.

Investigation on the mechanisms by which the herbal remedies induce anti-prostate cancer activity: uncovering the most practical natural compound.

Prostate cancer (PCa) is one of the most reported cancers among men worldwide. Targeting the essential proteins associated with PCa could be a promising method for cancer treatment. Traditional and herbal remedies (HRs) are the most practical approaches for PCa treatment. Here, the proteins and enzymes associated with PCa were determined based on the information obtained from the DisGeNET database. The proteins with a gene-disease association (GDA) score greater than 0.7 and the genes that have a disease specificity index (DSI) = 1 were selected as the target proteins. 28 HRs with anti-PCa activity as a traditional treatment for PCa were chosen as potential bioactive compounds. More than 500 compound-protein complexes were screened to find the top-ranked bioactives. The results were further evaluated using the molecular dynamics (MD) simulation and binding free energy calculations. The outcomes revealed that procyanidin B2 3,3'-di-O-gallate (B2G2), the most active ingredient of grape seed extract (GSE), can act as an agonist for PTEN. PTEN has a key role in suppressing PCa cells by applying phosphatase activity and inhibiting cell proliferation. B2G2 exhibited a considerable binding affinity to PTEN (11.643 kcal/mol). The MD results indicated that B2G2 could stabilize the key residues of the phosphatase domain of PTEN and increase its activity. Based on the obtained results, the active ingredient of GSE, B2G2, could play an agonist role and effectively increase the phosphatase activity of PTEN. The grape seed extract is a useful nutrition that can be used in men's diets to inhibit PCa in their bodies.Communicated by Ramaswamy H. Sarma.

Exploring the mechanism of probiotics in enhancing the utilization of chemical components (or polyphenols) of grape seed extract.

Fecal samples from 20 healthy adults were collected for in vitro fermentation experiments to investigate the effects of combined probiotics on the utilization of grape seed extract in humans. After fermenting for 24 h, short-chain fatty acids, metabolites, and gut microbiota composition were analyzed. Short-chain fatty acids in the grape seed extract probiotics group were significantly higher than those in the grape seed extract group. Probiotics significantly enhanced the conversion and utilization of catechins and epicatechins in grape seed extract group and increased the production of 3-hydroxyphenylacetic acid. The 16S rRNA sequencing results revealed that compound probiotics significantly increased the relative abundance of Lacticaseibacillus, HT002, Bifidobacterium, and Lactobacillus and reduced that of Escherichia-Shigella. Our findings showed considerable individual variability in the metabolic utilization of grape seed extract in humans. The consumption of probiotics appears to significantly enhance the utilization.