Effects of grape seed proanthocyanidin extract on cholesterol metabolism and antioxidant status in finishing pigs.

Grape seed proanthocyanidin extract (GSPE) is a natural polyphenolic compound, which plays an important role in anti-inflammatory and antioxidant. The present study aimed to investigate the effects of GSPE supplementation on the cholesterol metabolism and antioxidant status of finishing pigs. In longissimus dorse (LD) muscle, the data showed that GSPE significantly decreased the contents of total cholesterol (T-CHO) and triglyceride (TG), and decreased the mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and Fatty acid synthase (FAS), while increased the mRNA expression of carnitine palmitoyl transferase-1b (CPT1b), peroxisome proliferator-activated receptors (PPARα) and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). GSPE also reduced the enzyme activities of HMG-CoAR and FAS, and meanwhile amplified the activity of CPT1b in LD muscle of finishing pigs. Furthermore, dietary GSPE supplementation increased the serum catalase (CAT) and total antioxidant capacity (T-AOC), serum and liver total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) levels, while reduced serum and liver malondialdehyde (MDA) level in finishing pigs. In the liver, Superoxide Dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase 1 (GPX1), Nuclear Factor erythroid 2-Related Factor 2 (NRF2) mRNA levels were increased by GSPE. In conclusion, this study showed that GSPE might be an effective dietary supplement for improving cholesterol metabolism and antioxidant status in finishing pigs.

Proanthocyanidins alleviate Henoch-Schönlein purpura by mitigating inflammation and oxidative stress through regulation of the TLR4/MyD88/NF-κB pathway.

OBJECTIVE: Investigate Proanthocyanidins (PCs) efficacy and mechanisms in treating Henoch-Schönlein purpura (HSP)-like rat models, focusing on inflammatory and oxidative stress (OS) responses. METHODS: An HSP-like rat model was established using ovalbumin (OVA) injection, leading to symptoms mimicking HSP. The study measured inflammatory markers (IL-4, IL-17, TNF-α), OS markers (MDA, SOD, CAT), and assessed the TLR4/MyD88/NF-κB signaling pathway's involvement via histopathological and immunofluorescence analyses. RESULTS: PCs treatment significantly improved HSP-like symptoms, reduced inflammatory cell infiltration, and decreased IgA deposition in renal mesangial areas. Serum analyses revealed that PCs effectively lowered IL-4, IL-17, TNF-α, and MDA levels while increasing SOD and CAT levels (p < 0.05). Crucially, PCs also downregulated TLR4, MyD88, and NF-κB expressions, highlighting the blockage of the TLR4-mediated signaling pathway as a key mechanism. CONCLUSION: PCs show promising therapeutic effects in HSP-like rats by mitigating inflammatory responses and oxidative damage, primarily through inhibiting the TLR4/MyD88/NF-κB pathway. These findings suggest PCs as a potential treatment avenue for HSP, warranting further investigation.

Exploring the Interactions between Plant Proanthocyanidins and Thiabendazole: Insights from Isothermal Titration Calorimetry.

Anthelmintic resistance in gastrointestinal nematodes produces substantial challenges to agriculture, and new strategies for nematode control in livestock animals are called for. Natural compounds, including tannins, with proven anthelmintic activity could be a functional option as structurally diverse complementary compounds to be used alongside commercial anthelmintics. However, the dual use of two anthelmintic components requires an understanding of the pharmacological effects of the combination, while information concerning the interactions between plant-based polyphenols and commercial anthelmintics is scarce. We studied the direct interactions of proanthocyanidins (PAs, syn. condensed tannins) and a commercial anthelmintic thiabendazole, as a model substance of benzimidazoles, by isothermal titration calorimetry (ITC). Our results show evidence of a direct interaction of an exothermic nature with observed enthalpy changes ranging from 0 to -30 kJ/mol. The strength of the interaction between PAs and thiabendazole is mediated by structural characteristics of the PAs with the strongest positive correlation originating from the presence of galloyl groups and the increased degree of polymerization.

Halogenated Analogs to Natural A-Type Proanthocyanidins: Evaluation of Their Antioxidant and Antimicrobial Properties and Possible Application in Food Industries.

A description of new antimicrobial agents suitable for food industries has become necessary, and natural compounds are being considered as promising sources of new active derivatives to be used with the aim of improving food safety. We have previously described desirable antimicrobial and antibiofilm activities against foodborne bacteria by analogs to A-type proanthocyanidins (PACs) with a nitro (NO2) group at carbon 6 of the A-ring. We report herein the synthesis of eight additional analogs with chloro and bromo atoms at the A-ring and the systematic study of their antimicrobial and antioxidant activities in order to evaluate their possible application as biocides or food preservatives, as well as to elucidate new structure-activity relationships. The results from this study show that halogenated analogs to natural A-type proanthocyanidins rise above the nitro derivatives previously reported in their antimicrobial activities. Gram-positive bacteria are the most sensitive to all the analogs and combinations assayed, showing MICs from 10 to 50 µg/mL in most cases, as well as reductions in biofilm formation and the disruption of preformed biofilms of at least 75%. Some structure-activity relationships previously described have also been corroborated. Analogs with just one OH group at the B-ring show better antimicrobial activities than those with two OH groups, and those analogs with two or three OH groups in the whole structure are more active than those with four OH groups. In addition, the analogs with two OH groups at the B-ring and chloro at the A-ring are the most effective when antibiofilm activities are studied, especially at low concentrations.

Proanthocyanidins and ß-Glucan Synergistically Regulate Intestinal Inflammation in Dextran Sulfate Sodium-Induced Colitis Mice.

Proanthocyanidins (PA) have been proven to have an anti-inflammation effect in multiple models by regulating oxidative stress. ß-glucan (BG) could alleviate colitis from the perspectives of intestinal permeability and gut microbiota. In the present study, the synergistic anti-inflammatory function of PA and BG was explored from multiple aspects including immune response, intestinal barrier, gut microbiota, and differential metabolites. The results showed that the supplementation of PA and BG improved the colitis symptoms including atrophy of the colon, body weight loss, and organ index increase. Additionally, inflammatory cytokine levels and oxidative stress status were significantly regulated with the intake of PA and BG. Moreover, PA and BG intervention improved intestinal permeability and promoted the expression of barrier proteins. The microbiome and metabolic profile of cecal contents showed that PA and BG supplementation increased the abundance of anti-inflammatory bacteria and decreased the abundance of pro-inflammatory bacteria. Furthermore, some beneficial metabolites involved in amino acid metabolism, carbohydrate metabolism, and biosynthesis of other secondary metabolite pathways were increased. Overall, these findings have demonstrated the regulation of the inflammatory response and remodel of metabolite profiles by PA and BG complexes, indicating that it may serve as a new strategy for inflammatory bowel disease treatment in the future.

Time-of-Day Adrenal Modulation of Corticosterone Synthesis is Affected by Sex and Diet but Not by Proanthocyanidins in Rat.

SCOPE: The aim of this study is to investigate the effect of time-of-day on serum hormones and gene expression in adrenal glands, studying the impact of sex, obesogenic diet, and timing of proanthocyanidins administration, with a focus on glucocorticoids synthesis by this gland. METHODS AND RESULTS: Female and male rats, assigned to a standard chow or a cafeteria diet-fed group, receive a daily oral dose of a grape seed proanthocyanidin extract (GSPE), or a vehicle (when light is turned on, or when light is turned off). Corticosterone, estradiol, and testosterone serum levels, and the expression analysis of clock genes and genes related to corticosterone synthesis pathway, are assessed. Serum hormone levels exhibited a marked time-of-day effect also see in the expression of scavenger receptor class B member 1 (Scarb1) and cyp11b genes. The correlation between these two genes and period circadian regulator 2 (Per2) is also extended to other clock genes, although to a lesser extent: cryptochrome (Cry) and nuclear receptor subfamily 1 group D member 1 (Rev-erba). CONCLUSION: The strong correlations found suggest an important role of local Per2 (but also of Cry and Rev-erbA) in regulating the expression of the enzymes involved in the corticosterone synthesis pathway. The expression of clock genes in adrenals is influenced by sex and diet but not by GSPE.

Procyanidin B1 and p-coumaric acid from whole highland barley ameliorated HFD-induced impaired glucose tolerance via small intestinal barrier and hepatic glucose metabolism.

Highland barley is a natural source for the development of phenolic compounds that exhibit potential in preventing type 2 diabetes, which is important for the agricultural and industrial utilization of highland barley. However, very few studies have focused on their effect on small intestinal absorption and barrier dysfunction, as well as the direct target for the modulation of hepatic glucose metabolism. In this study, procyanidin B1 (PB) and p-coumaric acid (CA) isolated from highland barley supplementation in impaired glucose tolerance (IGT) mice significantly increased lactase-phlorizin hydrolase (LPH), sulfotransferase 1A1 (SULT1A1), UDP glucuronosyltransferase 1A (UGT1A) families and sodium-dependent glucose transporter 1 (SGLT1) expression in the small intestine of IGT mice, indicating beneficial effects on polyphenol deglycosylation and transportation. Supplementation with PB and CA also exhibited attenuation of small intestinal barrier dysfunction by improving the mucus layer and tight junctions, which was closely related to the transportation of phenolic compounds. In addition, PB and CA supplementation were explored directly to bind to the insulin receptor and activate the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, thereby modulating hepatic glucose metabolism and ameliorating hyperglycemic in IGT mice. These results offer crucial insights into the potential development of PB and CA as non-food nutraceuticals, as well as the extensive utilization of highland barley as an industrial crop.

Identification of procyanidins as α-glucosidase inhibitors, pancreatic lipase inhibitors, and antioxidants from the bark of Cinnamomum cassia by multi-bioactivity-labeled molecular networking.

This study examined the suppressive effects of 16 selected plant-based foods on α-glucosidase and pancreatic lipase and their antioxidant properties. Among these, the bark of Cinnamomum cassia (Cinnamon, WLN-FM 15) showed the highest inhibitory activity against α-glucosidase and the highest antioxidant activity. Additionally, WLN-FM 15 showed promising results in the other tests. To further identify the bioactive constituents of WLN-FM 15, a multi-bioactivity-labeled molecular networking approach was used through a combination of GNPS-based molecular networking, DPPH-HPLC, and affinity-based ultrafiltration-HPLC. A total of nine procyanidins were identified as antioxidants and inhibitors of α-glucosidase and pancreatic lipase in WLN-FM 15. Subsequently, procyanidins A1, A2, B1, and C1 were isolated, and their efficacy was confirmed through functional assays. In summary, WLN-FM 15 has the potential to serve as a functional food ingredient with the procyanidins as its bioactive constituents. These results also suggest that the multi-bioactivity-labeled molecular networking approach is reliable for identifying bioactive constituents in plant-based foods.

Purification of proanthocyanidins from nut seeds and study on its bactericidal mechanism against Streptococcus mutans.

AIM: The aim of this study was to purify proanthocyanidins from areca nut seeds (P-AN) and to investigate the bactericidal activity and mechanism of the purified products against Streptococcus mutans. METHODS AND RESULTS: Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry, Fourier transform infrared, Matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MADLI-TOF-MS), and thiolysis experiment were used for P-AN chemical analysis. Time-kill analysis and glycolytic pH drop were used to evaluate the activity of S. mutans in vitro. Meanwhile, the investigation of the bacteriostatic mechanism included membrane protein, fluidity, permeability, and integrity tests. The results showed that P-AN was a kind of proanthocyanidin mainly composed of B-type proanthocyanidins and their polymers. Moreover, MADLI-TOF-MS and thiolysis experiments demonstrated that the degree of polymerization of P-AN was 13. The time-kill analysis showed that P-AN had strong bactericidal activity against S. mutans. P-AN at minimum inhibitory concentration (MIC) concentrations was able to induce S. mutans death, while complete lethality occurred at 2 MIC. Glycolysis test showed that P-AN significantly inhibited S. mutans acid production (P < .01). The morphological changes of S. mutans were observed by scanning electron microscopy and transmission electron microscopy experiments, which indicated that P-AN destroyed the cellular structure of S. mutans. At the same time, significant changes were observed in membrane proteins, fluidity, permeability, and integrity. CONCLUSION: P-AN can effectively inhibit the activity of S. mutans. P-AN can reduce the erosion of the tooth surface by the acid of S. mutans. P-AN could break the structure of the cell membrane protein of S. mutans. P-AN could destroy the integrity of membrane, resulting in the death of S. mutans.

Enzyme-esterified grape seed proanthocyanidin derivatives as novel lipid-lowering agents.

Grape seed proanthocyanidin (GSP), as a natural antioxidant, has great potential to be developed into a lipid-lowering agent, but its low lipophilicity and stability greatly limit its application. In this study, an enzymatic esterification strategy was developed to introduce fatty acid chains into GSP, resulting in the successful synthesis of a series of new GSP derivatives. The results showed that up to 85% conversion of GSP and 35% TAG inhibition rate of GSP derivatives were achieved. The structures of GSP derivatives were identified by UPLC-MS/MS, and seven derivatives were confirmed as catechin-3'-O-laurate, epicatechin-3'-O-laurate, epicatechin gallate-3″,5″-di-O-laurate, epicatechin gallate-3',3″,5″-tri-O-laurate, procyanidin B1-3',3″-di-O-laurate, procyanidin B2-3',3″-di-O-laurate and procyanidin C1-3',3″,3‴-tri-O-laurate by NMR. GSP derivatives exhibited higher inhibitory effects on lipid accumulation, intracellular TAG and TC than parent GSP. These results indicate that GSP derivatives have potential as lipid-lowering agents for utilization in the food industry.

Procyanidin B2-3'-O-Gallate Derived from Grape Seed Polymeric Procyanidins via the Galloyl-Attached Nucleophilic Degradation as a Potential Hepatoprotective Agent.

An effective method was developed for preparing galloylated procyanidins (GPCs) using galloyl-attached nucleophilic degradation. Under degradation conditions optimized through Box-Behnken design and single-factor experiments, two dimeric and three tetrameric GPCs were produced, with the yield of procyanidin B2-3'-O-gallate (B2-3'-G) reaching up to 232 mg/g (PPCs). The structure of B2-3'-G was identified by UV, FTIR, NMR, CD, MS, and phloroglucinolysis. Furthermore, the protective effect of B2-3'-G against alcohol-induced liver injury (ALI) was investigated. Compared with the parent compounds, B2-3'-G exhibited a stronger capacity for inhibiting ALI, attributed to its polymerization degree and galloyl group. Subsequent experiments revealed that the pretreatment of BRL-3A cells with B2-3'-G prior to ethanol improved ALI through activation of the Nrf2-HO-1/NQO1 pathway and initiation of enzymatic antioxidant systems. These findings suggest that GPC B2-3'-G is a potential hepatoprotective agent, which provides a new perspective for functional development of GPCs.

Effects on dentin nanomechanical properties, cell viability and dentin wettability of a novel plant-derived biomodification monomer.

OBJECTIVES: To evaluate the effects of dentin biomodification agents (Proanthocyanidin (PAC), Cardol (CD) and Cardol-methacrylate (CDMA) on dentin hydrophilicity by contact angle measurement, viability of dental pulp stem cells (DPSCs) and nanomechanical properties of the hybrid layer (HL). METHODS: CDMA monomer was synthesized from cardol through methacrylic acid esterification. Human extracted third molars were used for all experiments. For nanomechanical tests, specimens were divided in four groups according to the primer solutions (CD, CDMA, PAC and control) were applied before adhesive and composite coating. Nanomechanical properties of the HL were analyzed by nanoindentation test using a Berkovich probe in a nanoindenter. Wettability test was performed on dentin surfaces after 1 min biomodification and measured by contact angle analysis. Cytotoxicity was assessed by a MTT assay with DPSCs after 48 and 72 h. Data were analyzed with Student's t test or Two-way ANOVA and Tukey HSD test (p < 0.05). RESULTS: CD and CDMA solutions achieved greater hydrophobicity and increased the water-surface contact angles when compared to PAC and control groups (p < 0.05). PAC group showed a greater reduction of elastic modulus in nanoindentation experiments when compared to CD and CDMA groups (p < 0.05) after 4 months of aging. CD inhibited cell proliferation compared to all further materials (p < 0.05), whilst CDMA and PAC indicated no cell cytotoxicity to human DPSCs. SIGNIFICANCE: Cardol-methacrylate provided significantly higher hydrophobicity to dentin and demonstrated remarkable potential as collagen crosslinking, attaining the lowest decrease of HL's mechanical properties. Furthermore, such monomer did not affect pulp cytotoxicity, thereby highlighting promising feasibility for clinical applications.

Comparison of microtensile bond strength of prepared teeth treated with proanthocyanidin, Camellia sinensis - Polyphenols, and metal crowns luted with resin-modified glass ionomer cement: An in vitro study.

AIM: The aim of this study was to evaluate the effect of proanthocyanidin and C. sinensis-polyphenols on microtensile bonding properties of prepared teeth with resin-modified glass ionomer cement (GIC). SETTING AND DESIGN: This was an in vitro study. MATERIALS AND METHODS: Seventy-eight maxillary premolars were selected and mounted into auto-polymerizing acrylic resin blocks. The samples were prepared and metal crowns were fabricated. The samples were randomly divided into three groups. Samples under Group 1 were not treated with any of the extracts and followed conventional bonding protocol. Samples under Group 2 and Group 3 were treated with proanthocyanidin and C. sinensis-polyphenols, respectively. After dentin treatment, these samples were luted to metal crowns using resin-modified GIC. Universal testing machine was used to measure the load at which the crowns were debonded and microtensile bond strength in MPa was calculated. STATISTICAL ANALYSIS: The results were statistically analyzed using one-way ANOVA and post hoc Tukey HSD. RESULTS: Samples treated with C. sinensis polyphenols (Group 3) had maximum bond strength followed by Group 2, where the samples were treated with proanthocyanidin. CONCLUSION: C. sinensis polyphenols due to their anti-proteolytic and antioxidant properties showed improved bond strength compared to proanthocyanidin, a cross-linking agent, followed by conventional bonding protocol.

Can the combination of proanthocyanidin and vitamin E or palm oil effectively protect enamel against in vitro erosive and abrasive challenges?

OBJECTIVES: This study aimed to assess the effect of proanthocyanidin, palm oil and vitamin E against erosive and erosive+abrasive challenges in vitro after enamel pellicle formation in situ. METHODOLOGY: Bovine enamel blocks (n=84) were obtained and divided into the following treatment groups: negative control (NC) - deionized water; positive control (PC) - SnCl2/NaF/AmF-containing solution; palm oil (PO); 2% proanthocyanidin (P2); vitamin E (VitE); 2% proanthocyanidin+palm oil (P2PO); and 2% proanthocyanidin+vitamin E (P2VitE). For 5 days, one half of the sample from each group was subjected to erosion and the other half was subjected to erosion+abrasion. The acquired enamel pellicle (AEP) was pre-formed in situ for 30 minutes. The specimens were then treated in vitro with solutions (500 µl, 30s for each group). Subsequently, the blocks were left in the oral cavity for another hour to obtain the modified AEP. The blocks were immersed in 0.5% citric acid (pH=2.5) for 90s, 4×/day. AEP formation and treatment were carried out before the first and third erosive challenges, and after these challenges, abrasive cycles (15s) were performed on half of the samples. Enamel wear was quantified by profilometry and data were analyzed by two-way ANOVA and Tukey's test (p<0.05). RESULTS: All groups showed higher wear when exposed to erosion+abrasion than when exposed to erosion alone (p=0.0001). PO, P2VitE, P2, and P2PO showed enamel wear similar to the PC group, but only PC, PO and P2VitE differed from the NC group. The other groups behaved similarly to NC. CONCLUSION: It was concluded that the combination of proanthocyanidin and vitamin E was effective in reducing wear in the face of in vitro erosive and erosive+abrasive challenges.

Limonium brasiliense rhizomes extract against virulence factors of Porphyromonas gingivalis: Inhibition of gingipains, bacterial adhesion, and biofilm formation.

Periodontitis is clinically characterized by destruction of the tooth support system and tooth loss. Porphyromonas gingivalis (Pg) plays a dominant role in periodontitis. Fractions and isolated compounds from an acetone-water extract of the roots of Limonium brasiliense (Lb) were tested in vitro for their anti-adhesive capacity against Pg on human KB buccal cells, influence on gingipains, the main virulence factors of Pg, and biofilm formation. Fractions EAF and FLB7 (50 µg/mL) reduced the bacterial adhesion of Pg to KB cells significantly (63 resp. 70%). The proanthocyanidin samarangenin A inhibited the adhesion (72%, 30 µM), samarangenin B (71%, 20 µM), and the flavan-3-ol epigallocatechin-3-O-gallate (79%, 30 µM). Fraction AQF, representing hydrophilic compounds, reduced the proteolytic activity of Arginin-specific gingipain (IC50 12.78 µg/mL). Fractions EAF and FLB7, characterized by lipohilic constituents, inhibited Arg-gingipain (IC50 3 µg/mL). On Lysine-specific gingipain, AQF has an IC50 15.89, EAF 14.15, and FLB7 6 µg/mL. The reduced bacterial adhesion is due to a strong interaction of proanthocyanidins with gingipains. AQF, EAF, and FLB7 significantly inhibited biofilm formation: IC50 11.34 (AQF), 11.66 (EAF), and 12.09 µg/mL (FLB7). In silico analysis indicated, that the polyphenols act against specific targets of Pg, not affecting mammalian cells. Therefore, Lb might be effective for prevention of periodontal disease by influencing virulence factors of Pg.

Structure-dependent capacity of procyanidin dimers to inhibit inflammation-induced barrier dysfunction in a cell model of intestinal epithelium.

Diet is of major importance in modulating intestinal inflammation, as the gastrointestinal tract is directly exposed to high concentrations of dietary components. Procyanidins are flavan-3-ol oligomers abundant in fruits and vegetables. Although with limited or no intestinal absorption, they can have GI health benefits which can promote overall health. We previously observed that epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) dimers inhibit in vitro colorectal cancer cell proliferation and invasiveness. Inflammation-mediated intestinal barrier permeabilization can result in a chronic inflammatory condition and promote colorectal cancer onset/progression. Thus, this study investigated the structure-dependent capacity of ECG, EGCG and (-)-epicatechin (EC) dimers to inhibit tumor necrosis factor alpha (TNFα)-induced inflammation, oxidative stress, and loss of barrier integrity in Caco-2 cells differentiated into an intestinal epithelial cell monolayer. Cells were incubated with TNFα (10 ng/ml), in the absence/presence of ECG, EGCG and EC dimers. The three dimers inhibited TNFα-mediated Caco-2 cell monolayer permeabilization, modulating events involved in the loss of barrier function and inflammation, i.e. decreased tight junction protein levels; increased matrix metalloproteinases expression and activity; increased NADPH oxidase expression and oxidant production; activation of the NF-κB and ERK1/2 pathways and downstream events leading to tight junction opening. For some of these mechanisms, the galloylated ECG and EGCG dimers had stronger protective potency than the non-galloylated EC dimer. These differences could be due to differential membrane interactions as pointed out by molecular dynamics simulation of procyanidin dimers-cell membrane interactions and/or by differential interactions with NOX1. Results show that dimeric procyanidins, although poorly absorbed, can promote health by alleviating intestinal inflammation, oxidative stress and barrier permeabilization.

Comparative Study of Condensed and Hydrolysable Tannins during the Early Stages of Zebrafish Development.

In this study, we present data on the effects of condensed tannins (CTs) and hydrolysable tannins (HTs), polyphenols extracted from plants, at different concentrations on zebrafish development to identify the range of concentrations with toxic effects. Zebrafish embryos were exposed to CTs and HTs at two different concentration ranges (5.0-20.0 µgL-1 and 5.0-20.0 mgL-1) for 72 h. The toxicity parameters were observed up to 72 h of treatment. The uptake of CTs and HTs by the zebrafish larvae was assessed via HPLC analysis. A qRT-PCR analysis was performed to evaluate the expressions of genes cd63, zhe1, and klf4, involved in the hatching process of zebrafish. CTs and HTs at 5.0, 10.0, and 20.0 µgL-1 were not toxic. On the contrary, at 5.0, 10.0, and 20.0 mgL-1, HTs induced a delay in hatching starting from 48 h of treatment, while CTs showed a delay in hatching mainly at 48 h. The analysis of gene expression showed a downregulation in the group exposed to HTs, confirming the hatching data. We believe that this study is important for defining the optimal doses of CTs and HTs to be employed in different application fields such as the chemical industry, the animal feed industry, and medical science.

The Novel A-Type Proanthocyanidin-Rich Phytocomplex SP4™ Acts as a Broad-Spectrum Antiviral Agent against Human Respiratory Viruses.

The appearance of new respiratory virus infections in humans with epidemic or pandemic potential has underscored the urgent need for effective broad-spectrum antivirals (BSAs). Bioactive compounds derived from plants may provide a natural source of new BSA candidates. Here, we investigated the novel phytocomplex formulation SP4™ as a candidate direct-acting BSA against major current human respiratory viruses, including coronaviruses and influenza viruses. SP4™ inhibited the in vitro replication of SARS-CoV-2, hCoV-OC43, hCoV-229E, Influenza A and B viruses, and respiratory syncytial virus in the low-microgram range. Using hCoV-OC43 as a representative respiratory virus, most of the antiviral activity of SP4™ was observed to stem primarily from its dimeric A-type proanthocyanidin (PAC-A) component. Further investigations of the mechanistic mode of action showed SP4™ and its PAC-A-rich fraction to prevent hCoV-OC43 from attaching to target cells and exert virucidal activity. This occurred through their interaction with the spike protein of hCoV-OC43 and SARS-CoV-2, thereby interfering with spike functions and leading to the loss of virion infectivity. Overall, these findings support the further development of SP4™ as a candidate BSA of a natural origin for the prevention of human respiratory virus infections.

Grape Seed Proanthocyanidin Extract Attenuates Cafeteria-Diet-Induced Liver Metabolic Disturbances in Rats: Influence of Photoperiod.

This study investigated the influence of photoperiod (day length) on the efficacy of grape seed proanthocyanidin extract (GSPE) in mitigating metabolic disorders in obese rats fed a cafeteria diet. Rats were exposed to standard (L12), long (L18), or short (L6) photoperiods and treated with GSPE or vehicle. In the standard photoperiod, GSPE reduced body weight gain (50.5%), total cholesterol (37%), and triglycerides (34.8%), while increasing the expression of hepatic metabolic genes. In the long photoperiod, GSPE tended to decrease body weight gain, increased testosterone levels (68.3%), decreased liver weight (12.4%), and decreased reverse serum amino acids. In the short photoperiod, GSPE reduced glycemia (~10%) and lowered triglyceride levels (38.5%), with effects modified by diet. The standard photoperiod showed the greatest efficacy against metabolic syndrome-associated diseases. The study showed how day length affects GSPE's benefits and underscores considering biological rhythms in metabolic disease therapies.

Proanthocyanidin alleviates testicular torsion/detorsion-induced ischemia/reperfusion injury in rats.

Testicular torsion is an urological emergency and can lead to ischemia damage and testicular loss if not diagnosed in time. Proanthocyanidin is reported to have anti-inflammatory and antioxidant properties. The current study aimed to examine the possible effects of proanthocyanidin (P) on the testis in torsion/detorsion (T/D)-induced testicular ischemia/reperfusion (I/R) injury in rats. Forty rats were divided into four groups (n=10 for each): sham-operated (sham), I/R, I/R + P100 (100 mg/kg, 30 min before torsion), and I/R + P200 (200 mg/kg, 30 min before torsion). Testicular T/D was performed on the left testicle by 3 hours of torsion at 720° clockwise, followed by 3 hours of detorsion. In the I/R group, an increase in malondialdehyde (MDA) levels and a decrease in glutathione (GSH), vitamin C (Vit C), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD) values were determined compared to the sham group (p<0.001). Moreover, an increase in the expression of cleaved caspase-3 and Bcl2-associated X protein (Bax), a decrease in the expression of B-cell lymphoma 2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) were detected in the I/R group (p<0.001). Histopathologically, it was determined that the Johnsen and Cosentino scores of the testicles were irregular in the I/R group (p<0.001). Proanthocyanidin treatment caused a decrease in MDA, cleaved caspase-3 and Bax levels and an increase in GSH, Vit C, GPx, G6PD, Bcl-2 and PCNA values. Additionally, Johnsen and Cosentino rearranged the scores. The present findings revealed the protective and curative effects of proanthocyanidin in organ damage due to testicular torsion/detorsion-induced ischemia/reperfusion with their antioxidative and antiapoptotic properties.