Procyanidin C1 inhibits bleomycin-induced pulmonary fibrosis in mice by selective clearance of senescent myofibroblasts.

Pulmonary fibrosis is a formidable challenge in chronic and age-related lung diseases. Myofibroblasts secrete large amounts of extracellular matrix and induce pro-repair responses during normal wound healing. Successful tissue repair results in termination of myofibroblast activity via apoptosis; however, some myofibroblasts exhibit a senescent phenotype and escape apoptosis, causing over-repair that is characterized by pathological fibrotic scarring. Therefore, the removal of senescent myofibroblasts using senolytics is an important method for the treatment of pulmonary fibrosis. Procyanidin C1 (PCC1) has recently been discovered as a senolytic compound with very low toxicity and few side effects. This study aimed to determine whether PCC1 could improve lung fibrosis by promoting apoptosis in senescent myofibroblasts and to investigate the mechanisms involved. The results showed that PCC1 attenuates bleomycin (BLM)-induced pulmonary fibrosis in mice. In addition, we found that PCC1 inhibited extracellular matrix deposition and promoted the apoptosis of senescent myofibroblasts by increasing PUMA expression and activating the BAX signaling pathway. Our findings represent a new method of pulmonary fibrosis management and emphasize the potential of PCC1 as a senotherapeutic agent for the treatment of pulmonary fibrosis, providing hope for patients with pulmonary fibrosis worldwide. Our results advance our understanding of age-related diseases and highlight the importance of addressing cellular senescence in treatment.

Procyanidin B1 and Coumaric Acid from Highland Barley Alleviated High-Fat-Diet-Induced Hyperlipidemia by Regulating PPARα-Mediated Hepatic Lipid Metabolism and Gut Microbiota in Diabetic C57BL/6J Mice.

A whole-grain highland barley (WHB) diet has been recognized to exhibit the potential for alleviating hyperlipidemia, which is mainly characterized by lipids accumulation in the serum and liver. Previously, procyanidin B1 (PB) and coumaric acid (CA) from WHB were found to alleviate serum lipid accumulation in impaired glucose tolerance mice, while the effect on modulating the hepatic lipid metabolism remains unknown. In this study, the results showed the supplementation of PB and CA activated the expression of peroxisome proliferator-activated receptor α (PPARα) and the target genes of cholesterol 7-α hydroxylase (CYP7A1) and carnitine palmitoyl transferase I (Cpt1) in the liver cells of high-fat-diet (HFD)-induced diabetic C57BL/6J mice, resulting in decreases in the serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL-C) contents, and an increase in the high-density lipoprotein (HDL-C) content. High-throughput sequencing of 16S rRNA indicated that supplementation with PB and CA ameliorated the gut microbiota dysbiosis, which was associated with a reduction in the relative abundance of Ruminococcaceae and an increase in the relative abundance of Lactobacillus, Desulfovibrio, and Akkermansia. Spearman's correlation analysis revealed that these genera were closely related to obesity-related indices. In summary, the activation of PPARα expression by PB and CA from WHB was important for the alleviation of hyperlipidemia and the structural adjustment of the gut microbiota.

Controlled delivery of procyanidin through magnesium oxide nanoparticles (MgO NPs) to improve the activity and mineralization of osteoblasts under oxidative stressin vitro.

Excessive reactive oxygen species (ROS) in the microenvironment of osteoporosis (OP) not only accelerate the bone absorption, but also affect the osteogenic and mineralized effect of osteoblasts. Procyanidins (PC) have been reported to have anti-oxidation effects, but low bioavailability. This study aimed to explore the effect of magnesium oxide nanoparticles (MgO-PC NPs)-loaded PC on the osteogenesis and mineralization of osteoblasts that stimulated by H2O2. PC was loaded onto MgO NPs and characterized by transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. After primary screening by cytotoxicity assay, MgO-PC NPs containing 20 µM of PC were chosen for further studies. In H2O2-stimulated osteoblasts, dichlorodihydrofluorescein diacetate probe, Cell Counting Kit-8, quantitative real-time polymerase chain reaction, alkaline phosphatase staining/activity and Alizarin red staining were used to detect the ROS production, cell viability and osteogenic and mineralized markers of osteoblasts. PC was loaded onto MgO NPs to successfully receive MgO-PC NPs with a diameter of about 144 nm and negative potential. PC can sustain release from MgO-PC NPs for at least 16 d. The controlled release of PC from MgO-PC NPs can effectively eliminate ROS and thereby promoted the cell activity. Most importantly, the osteogenesis and mineralization of osteoblasts under oxidative stress were also significantly reversed by MgO-PC NPS. Thus, these findings indicate that MgO-PC NPs may be developed as a potential therapeutic strategy for OP.

Optimization and Validation of Procyanidins Extraction and Phytochemical Profiling of Seven Herbal Matrices of Nutraceutical Interest.

Several medicinal herbal plants are extensively used as sources of bioactive compounds with beneficial effects on human health. This study assessed the procyanidin and polyphenol profiles together with the antioxidant potential of seven herbal medical matrices. To achieve this aim, procyanidin extraction from grape pomace was optimized and validated by monitoring monomeric-trimeric procyanidins. The proposed quantification method was applied to the seven medical herbs, and it proved to be a very efficient protocol for procyanidin-rich extracts analysis. In addition, the Paullinia cupana Kunth. seed was identified as a very rich source of procyanidins (about 5 mg/g dry matrix of each dimeric and about 3 mg/g dry matrix trimeric) with high antioxidant properties. The polyphenolic profile was assessed by HPLC-HESI-MS/MS analysis. The in vitro antioxidant activity was evaluated by DPPH assay to explore the antioxidant properties of the extracts, which were substantially higher in Peumus boldus Molina leaves extracts (935.23 ± 169 µmol of Trolox equivalent/g of dry weight) concerning the other matrices. Moreover, a high Pearson coefficient value was observed between the total flavonoid content (TFC) and DPPH in comparison with the total polyphenol content (TPC) and DPPH, indicating flavonoids as the principal bioactive with antioxidant activity in the extracts.

Glucose-modified BSA/procyanidin C1 NPs penetrate the blood-brain barrier and alleviate neuroinflammation in Alzheimer's disease models.

Alzheimer's disease (AD) is a chronic neurodegenerative disease with high prevalence, long duration and poor prognosis. The blood-brain barrier (BBB) is a physiologic barrier in the central nervous system, which hinders the entry of most drugs into the brain from the blood, thus affecting the efficacy of drugs for AD. Natural products are recognized as one of the promising and unique therapeutic approaches to treat AD. To improve the efficiency and therapeutic effect of the drug across the BBB, a natural polyphenolic compound, procyanidin C-1 (C1) was encapsulated in glucose-functionalized bovine serum albumin (BSA) nanoparticles to construct Glu-BSA/C1 NPs in our study. Glu-BSA/C1 NPs exhibited good stability, slow release, biocompatibility and antioxidant properties. In addition, Glu-BSA/C1 NPs penetrated the BBB, accumulated in the brain by targeting Glut1, and maintained the BBB integrity both in vitro and in vivo. Moreover, Glu-BSA/C1 NPs alleviated memory impairment of 5 × FAD mice by reducing Aß deposition and Tau phosphorylation and promoting neurogenesis. Mechanistically, Glu-BSA/C1 NPs significantly activated the PI3K/AKT pathway and inhibited the NLRP3/Caspase-1/IL-1ß pathway thereby suppressing neuroinflammation. Taken together, Glu-BSA/C1 NPs could penetrate the BBB and mitigate neuroinflammation in AD, which provides a new therapeutic approach targeting AD.

Procyanidin B2 alleviates oxidized low-density lipoprotein-induced cell injury, inflammation, monocyte chemotaxis, and oxidative stress by inhibiting the nuclear factor kappa-B pathway in human umbilical vein endothelial cells.

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) can initiate and affect almost all atherosclerotic events including endothelial dysfunction. In this text, the role and underlying molecular basis of procyanidin B2 (PCB2) with potential anti-oxidant and anti-inflammatory activities in ox-LDL-induced HUVEC injury were examined. METHODS: HUVECs were treated with ox-LDL in the presence or absence of PCB2. Cell viability and apoptotic rate were examined by CCK-8 assay and flow cytometry, respectively. The mRNA and protein levels of genes were tested by RT-qPCR and western blot assays, respectively. Potential downstream targets and pathways of apple procyanidin oligomers were examined by bioinformatics analysis for the GSE9647 dataset. The effect of PCB2 on THP-1 cell migration was examined by recruitment assay. The effect of PCB2 on oxidative stress was assessed by reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and mitochondrial membrane potential (MMP). RESULTS: ox-LDL reduced cell viability, induced cell apoptosis, and facilitated the expression of oxidized low-density lipoprotein receptor 1 (LOX-1), C-C motif chemokine ligand 2 (MCP-1), vascular cell adhesion protein 1 (VCAM-1) in HUVECs. PCB2 alleviated ox-LDL-induced cell injury in HUVECs. Apple procyanidin oligomers triggered the differential expression of 592 genes in HUVECs (|log2fold-change| > 0.58 and adjusted p-value < 0.05). These dysregulated genes might be implicated in apoptosis, endothelial cell proliferation, inflammation, and monocyte chemotaxis. PCB2 inhibited C-X-C motif chemokine ligand 1/8 (CXCL1/8) expression and THP-1 cell recruitment in ox-LDL-stimulated HUVECs. PCB2 inhibited ox-LDL-induced oxidative stress and nuclear factor kappa-B (NF-κB) activation in HUVECs. CONCLUSION: PCB2 weakened ox-LDL-induced cell injury, inflammation, monocyte recruitment, and oxidative stress by inhibiting the NF-κB pathway in HUVECs.

Proanthocyanidins and Phenolic Compounds from the Twigs of Salix chaenomeloides and Their Anti-Lipogenic Effects on 3T3-L1 Preadipocytes.

The present study investigated potential bioactive natural products from the EtOH extract of Salix chaenomeloides twigs using column chromatography, leading to the isolation of six compounds (1-6), which were characterized as two proanthocyanidins, procyanidin B2 (1) and procyanidin B1 (2), and four phenolic compounds, 4-hydroxybenzoic acid ß-D-glucosyl ester (3), di-O-methylcrenatin (4), p-coumaric acid glucoside (5), and syringin (6) by the comparison of their NMR spectra with the reported data and high-resolution (HR)-electrospray ionization mass spectroscopy (ESI-MS) analysis. We investigated the potential of six compounds (1-6) to inhibit adipogenesis in 3T3-L1 preadipocytes, which showed that the compounds (1-6) significantly reduced lipid accumulation in 3T3-L1 adipocytes without affecting cell proliferation. Notably, compound 1 demonstrated a remarkable 60% and 90% reduction in lipid levels with 50 and 100 µM treatments, respectively. Oil Red O staining results indicated that compound 1 significantly inhibits the formation of lipid droplets, comparable to the effect of T863, an inhibitor of triglyceride used as a positive control, in adipocytes. Compound 1 had no effect on the regulators PPARγ, C/EBPα, and SREBF1 of adipocyte differentiation in 3T3-L1 preadipocytes, but compound 1 activated the fatty acid oxidation regulator, PPARα, compared to the lipogenic-induced control. It also suppressed fatty acid synthesis by downregulating the expression of fatty acid synthase (FAS). Finally, compound 1 induced the mRNA and protein levels of CPT1A, an initial marker of mitochondrial fatty acid oxidation in 3T3-L1. This finding substantiates the anti-lipogenic and lipolytic effects of procyanidin B2 (1) in 3T3-L1 preadipocytes, emphasizing its pivotal role in modulating obesity-related markers.

Grape seed proanthocyanins protect fluoride-induced hepatotoxicity via the Nrf2 signaling pathway in male rats.

Background: Fluoride is a necessary element for human health, but excessive fluoride intake is found toxic to the liver. Previous studies confirmed that Grape seed procyanidin extract (GSPE) protects against fluoride-induced hepatic injury. However, the mechanism underlying this protective effect remains obscure. To evaluate the protective effect of GSPE against fluoride-induced hepatic injury and explore the possible hepatoprotective role of the Nrf2 signaling pathway to find effective strategies for the treatment and prevention of fluoride-induced hepatotoxicity. This study aims to explore the mechanisms by which GSPE attenuates fluoride-induced hepatotoxicity through a rat drinking water poisoning model. Methods: Hepatic injury was determined by serum biochemical parameters, oxidative parameters, HE, and TUNEL analysis. The protein expression levels of apoptosis-related proteins like Bax, B-cell lymphoma-2 (Bcl-2), and Caspase-3 and the nuclear factor, erythroid 2 like 2 (Nrf2) were analyzed by Western blot. Resluts: Our results showed that GSPE administration reduced fluoride-induced elevated serum ALT and AST and enhanced the antioxidant capacity of the liver. In addition, GSPE mitigated fluoride-induced histopathological damage and reduced the liver cell apoptosis rate. Furthermore, GSPE significantly up-regulated the expression and nuclear translocation of the Nrf2 and decreased apoptosis-related proteins like Bax and caspase-3 in the hepatic. Conclusion: Taken together, GSPE exerts protective effects on the oxidative damage and apoptosis of fluoride-induced hepatic injury via the activation of the Nrf2 signaling pathway. This study provides a new perspective for the mechanism study and scientific prevention and treatment of liver injury induced by endemic fluorosis.

Synergistic anti-diabetic effect of phloroglucinol and total procyanidin dimer isolated from Vitisvinifera methanolic seed extract potentiates via suppressing oxidative stress: in-vitro evaluation studies.

Diabetes is often associated with increased oxidative stress caused by an imbalance between detoxification and ROS production. Unfortunately, many commercial drugs available today for treating this disease have adverse side effects and ultimately fail to restore glucose homeostasis. Therefore, finding a dietary anti-diabetic remedy that is safe, effective, and economical is crucial. In this study, GC-MS analysis, subsequent HPLC-assisted fractionation, and SPE-based purification led to identifying and purifying of key components such as phloroglucinol and total procyanidin dimer (procyanidin dimer and procyanidin dimer gallate) from methanolic seed extract of Vitis vinifera. In-vitro anti-diabetic screening of various fractions derived from methanolic extract along with individual components and their combinations revealed the potential synergistic behaviour of phloroglucinol and total procyanidin dimer with the lowest IC50 of 48.21 ± 3.54 µg/mL for α-glucosidase and 63.06 ± 5.38 µg/mL for α-amylase inhibition which is found to be superior to the effect shown by the standard Epigallocatechin gallate. Later Glucose utilization studies demonstrated the concentration-dependent effect of Phloroglucinol and total procyanidin dimer, and that has raised the glucose uptake by approximately 36-57% in HepG2 cells and 35-58% in L6 myocytes over a concentration of 50-100 µg/mL. The superior anti-diabetic effect of Phloroglucinol and total procyanidin dimer was proved by the suppression of oxidative stress with an IC50 of 7.92 ± 0.36 µg/mL for DPPH scavenging and 16.87 ± 1.24 µg/mL for SOD scavenging which is competent with the standard ascorbic acid. According to this study, suppressing ROS levels by phloroglucinol and total procyanidin dimer would be the underlying mechanism for the synergistic anti-diabetic effect of this combination. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03929-4.

Novel l-Cysteine Incomplete Degradation Method for Preparation of Procyanidin B2-3'-O-Gallate and Exploration of its in Vitro Anti-inflammatory Activity and in Vivo Tissue Distribution.

In this study, an effective method for preparation of bioactive galloylated procyanidin B2-3'-O-gallate (B2-3'-G) was first developed by incomplete depolymerization of grape seed polymeric procyanidins (PPCs) using l-cysteine (Cys) in the presence of citric acid. The structure-activity relationship of B2-3'-G was further evaluated in vitro through establishing lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. The results suggested that the better protective effects of B2-3'-G against inflammation were attributed to its polymerization degree and the introduction of the galloyl group, compared to its four corresponding structural units. In vivo experiments demonstrated that the B2-3'-G prototype was distributed in plasma, small intestine, liver, lung, and brain. Remarkably, B2-3'-G was able to penetrate the blood-brain barrier and appeared to play an important role in improving brain health. Furthermore, a total of 18 metabolites were identified in tissues. Potential metabolic pathways, including reduction, methylation, hydration, desaturation, glucuronide conjugation, and sulfation, were suggested.

Aromatase inhibitors identified from Saraca asoca to treat infertility in women with polycystic ovary syndrome via in silico and in vivo studies.

Polycystic ovary syndrome (PCOS) is a widely occurring metabolic disorder causing infertility in 70%-80% of the affected women. Saraca asoca, an ancient medicinal herb, has been shown to have therapeutic effects against infertility and hormonal imbalance in women. This study was aimed to identify new aromatase inhibitors from S. asoca as an alternative to the commercially available ones via in silico and in vivo approaches. For this, 10 previously reported flavonoids from S. asoca were chosen and the pharmacodynamic and pharmacokinetic properties were predicted using tools like Autodock Vina, GROMACS, Gaussian and ADMETLab. Of the 10, procyanidin B2 and luteolin showed better interaction with higher binding energy when docked against aromatase (3S79) as compared to the commercial inhibitor letrozole. These two compounds showed higher stability in molecular dynamic simulations performed for 100 ns. Molecular mechanics Poisson-Boltzmann surface analysis indicated that these compounds have binding free energy similar to the commercial inhibitor, highlighting their great affinity for aromatase. Density functional theory analysis revealed that both compounds have a good energy gap, and ADMET prediction exhibited the drug-likeness of the two compounds. A dose-dependent administration of these two compounds on zebrafish revealed that both the compounds, at a lower concentration of 50 µg/ml, significantly reduced the aromatase concentration in the ovarian tissues as compared to the untreated control. Collectively, the in silico and in vivo findings recommend that procyanidin B2 and luteolin could be used as potential aromatase inhibitors for overcoming infertility in PCOS patients with estrogen dominance.Communicated by Ramaswamy H. Sarma.

The profiles of free, esterified and insoluble-bound phenolics in peach juice after high pressure homogenization and evaluation of their antioxidant capacities, cytoprotective effect, and inhibitory effects on α-glucosidase and dipeptidyl peptidase-â £.

The phenolic profiles, antioxidant capacities, cytoprotective effect, and α-glucosidase and DPP-IV inhibitory capacity of free (FP), esterified (EP) and insoluble-bound (IBP) phenolic fractions in 'Lijiang snow' peach juice after high pressure homogenization (HPH) were investigated, and the molecular docking was used to explore the enzyme inhibition mechanism. HPH increased total phenolic and total flavonoid contents in three fractions without changing compositions. The IC50 of radicals scavenged by three fractions were all reduced by HPH. The best inhibition on intracellular ROS production were found for phenolic fractions after HPH at 300 MPa, with ROS levels ranged within 95.26-119.16 %. HPH at 300 MPa reduced the apoptosis rates of FP and EP by 16.52 % and 9.33 %, respectively. All phenolic fractions showed effective inhibition on α-glucosidase and DPP-IV by formation of hydrogen bonding and van der Waals forces. This study explored the feasibility of HPH to enhance the phenolics and bioactivity of peach juice.

Targeting CD38/ ADP-ribosyl cyclase as a novel therapeutic strategy for identification of three potent agonists for leukopenia treatment.

Leukopenia is the most common side effect of chemotherapy and radiotherapy. It potentially deteriorates into a life-threatening complication in cancer patients. Despite several agents being approved for clinical administration, there are still high incidences of pathogen-related disease due to a lack of functional immune cells. ADP-ribosyl cyclase of CD38 displays a regulatory effect on leukopoiesis and the immune system. To explore whether the ADP-ribosyl cyclase was a potential therapeutic target of leukopenia. We established a drug screening model based on an ADP-ribosyl cyclase-based pharmacophore generation algorithm and discovered three novel ADP-ribosyl cyclase agonists: ziyuglycoside II (ZGSII), brevifolincarboxylic acid (BA), and 3,4-dihydroxy-5-methoxybenzoic acid (DMA). Then, in vitro experiments demonstrated that these three natural compounds significantly promoted myeloid differentiation and antibacterial activity in NB4 cells. In vivo, experiments confirmed that the compounds also stimulated the recovery of leukocytes in irradiation-induced mice and zebrafish. The mechanism was investigated by network pharmacology, and the top 12 biological processes and the top 20 signaling pathways were obtained by intersecting target genes among ZGSII, BA, DMA, and leukopenia. The potential signaling molecules involved were further explored through experiments. Finally, the ADP-ribosyl cyclase agonists (ZGSII, BA, and DMA) has been found to regenerate microbicidal myeloid cells to effectively ameliorate leukopenia-associated infection by activating CD38/ADP-ribosyl cyclase-Ca2+-NFAT. In summary, this study constructs a drug screening model to discover active compounds against leukopenia, reveals the critical roles of ADP-ribosyl cyclase in promoting myeloid differentiation and the immune response, and provides a promising strategy for the treatment of radiation-induced leukopenia.

Electrochemical determination of the procyanidins in peanut skin using a carbon nanotube electrode.

We demonstrated the electrochemical detection of procyanidins in peanut skin, which is often a waste product of the food industry, using a carbon nanotube electrode. Procyanidins, the main ingredients of peanut skin, are oligomers of catechin or epicatechin; therefore, they have various forms such as dimers, trimers, and a different number of linkages between monomers. Quantification using traditional high-performance liquid chromatography-mass spectroscopy (HPLC-MS) is tedious, because many peaks can be traced. The use of CNT electrodes for procyanidin sensing is promising, because CNT's properties, such as high conductivity, catalytic ability, and special geometry (high ratio of surface area to volume), enable common and specific profiles of the cyclic voltammograms (CVs) of procyanidins. Furthermore, the intensity of the anodic peaks (+ 0.32 V) due to the oxidation of catechol groups is proportional to the concentration of procyanidin (linear rang: 2.8-88 mg L-1, sensitivity: 1.4 mA mg-1 L cm-2), and does not depend on the type of procyanidin. The amount of procyanidins in the peanut skin estimated by CV was similar to that estimated by HPLC-MS. This study may contribute to accelerating the utilization of peanut skin for animal food, drugs, and supplementation.

Antibacterial and antioxidant activities of a novel biosynthesized selenium nanoparticles using Rosa roxburghii extract and chitosan: Preparation, characterization, properties, and mechanisms.

Developing efficient and safe antibacterial agents to inhibit pathogens including Physalospora piricola and Staphylococcus aureus is of great importance. Herein, a novel compound composed of Rosa roxburghii procyanidin, chitosan and selenium nanoparticle (RC-SeNP) was bio-synthesized, with the average diameter and zeta potential being 84.56 nm and -25.60 mV, respectively. The inhibition diameter of the RC-SeNP against P. piricola and S. aureus reached 18.67 mm and 13.13 mm, and the maximum scavenging activity against DPPH and ABTS reached 96.02% and 98.92%, respectively. Moreover, the RC-SeNP completely inhibited the propagation P. piricola and S. aureus on actual apples, suggesting excellent in vivo antimicrobial capacity. The transcriptome analysis and electron microscope observation indicated that the antibacterial activity would be attributed to adhering to and crack the cell walls as well as damage the cytomembrane and nucleus. Moreover, the RC-SeNP effectively maintained the vitamin C, total acid, and water contents of red bayberry, demonstrating potential application for fruit preservation. At last, the RC-SeNP showed no cell toxicity and trace selenium residual dose (0.03 mg/kg on apple, 0.12 mg/kg on red bayberry). This study would enlighten future development on novel nano-bioantibacterial agents for sustainable agriculture.

Investigation of peanut allergen-procyanidin non-covalent interactions: Impact on protein structure and in vitro allergenicity.

Interactions between plant polyphenols and food allergens may be a new way to alleviate food allergies. The non-covalent interactions between the major allergen from peanut (Ara h 2) with procyanidin dimer (PA2) were therefore characterized using spectroscopic, thermodynamic, and molecular simulation analyses. The main interaction between the Ara h 2 and PA2 was hydrogen bonding. PA2 statically quenched the intrinsic fluorescence intensity and altered the conformation of the Ara h 2, leading to a more disordered polypeptide structure with a lower surface hydrophobicity. In addition, the in vitro allergenicity of the Ara h 2-PA2 complex was investigated using enzyme-linked immunosorbent assay (ELISA) kits. The immunoglobulin E (IgE) binding capacity of Ara h 2, as well as the release of allergenic cytokines, decreased after interacting with PA2. When the ratio of Ara h 2-to-PA2 was 1:50, the IgE binding capacity was reduced by around 43 %. This study provides valuable insights into the non-covalent interactions between Ara h 2 and PA2, as well as the potential mechanism of action of the anti-allergic reaction caused by binding of the polyphenols to the allergens.

Phytochemical investigation and antioxidant properties of unripe tomato cultivars (Solanum lycopersicum L.).

Unripe tomatoes are among the main waste produced during tomato cultivation and processing. In this study, unripe tomatoes from seven different Italian cultivars have been investigated to evaluate their nutraceutical potential. Phytochemical investigation allowed shedding light on the identification of seventy-five bioactive compounds. The highest amount of polyphenolic and glycoalkaloids along with the high level of antioxidant activities was found in the Datterini tomatoes variety. The peculiarity of this variety is the high chlorogenic acid content, being ten times higher compared to the other cultivars examined. Moreover, the total α-tomatine amount has been found substantially higher (34.699 ± 1.101 mg/g dry weight) with respect to the other tomato varieties analyzed. Furthermore, the cultivars metabolomic profiles were investigated with the PCA approach. Based on Datterini cultivar's metabolomic profile, its waste-recovery could represent a good option for further added value products in pharmaceutical and nutraceutical areas with a high α-tomatine content.

Effect mechanism research of procyanidin on gingivitis rats by regulating the PI3K/Akt/VEGF signal pathway / 中国药房

OBJECTIVE To investigate the potential mechanism of procyanidin on rats with gingivitis by regulating phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/vascular endothelial growth factor （VEGF） signaling pathway. METHODS The rat model of gingivitis was constructed by sewing the neck of the first maxillary molar with silk thread+applying maltose on the gum+feeding with 20% sucrose solution and soft food. Forth-eight model rats were randomly divided into model group， procyanidin group （160 mg/kg）， 740Y-P group （PI3K/Akt signaling pathway activator， 0.02 mg/kg）， and procyanidin+ 740Y-P group （procyanidin 160 mg/kg+740Y-P 0.02 mg/kg）， with 12 rats in each group； another 12 rats were selected as control group； each medication group was treated with corresponding drugs intragastrically or/and intraperitoneally， once a day， for 7 consecutive days. Twenty-four hours after the last administration， the gingival index of rats was measured； the levels of interleukin- 18 （IL-18）， inducible nitric oxide synthase （iNOS） and alkaline phosphatase （ALP） in gingival crevicular fluid， as well as the levels of superoxide dismutase （SOD）， catalase （CAT） and reactive oxygen species （ROS） in gingival tissues of rats were detected； the pathological changes in gingival tissues were observed； the expression levels of PI3K/Akt/VEGF signaling pathway- related proteins in gingival tissues of rats were detected. RESULTS Compared with control group， the gingival tissues of rats in the model group had severe pathological damage，which was manifested as local tissue expansion and congestion， new capillaries， degeneration and loss of collagen fibers and disorder of arrangement， and a large number of inflammatory cell infiltration in the gingival sulcus wall. The gingival index， the levels of IL-18， iNOS， ALP in gingival crevicular fluid， the level of ROS in gingival tissues， the phosphorylations of PI3K and Akt， as well as the protein expression of VEGF in gingival tissues were significantly increased； the levels of SOD and CAT in gingival tissues of rats in model group were significantly decreased （P＜0.05）. Compared with model group， the pathological damage to the gingival tissues of rats in procyanidin group was reduced， and all quantitative indicators were significantly improved （P＜0.05）； 740Y-P could reverse the improvement effect of procyanidin on various indicators （P＜0.05）. CONCLUSIONS Procyanidin may alleviate gingival tissue damage， and improve gingival inflammation and oxidative stress in rats with gingivitis by inhibiting PI3K/Akt/VEGF signaling pathway.

Grape seed-derived procyanidin inhibits glyphosate-induced hepatocyte ferroptosis via enhancing crosstalk between Nrf2 and FGF12.

BACKGROUND: Glyphosate (GLY) exposure induces hepatocyte ferroptosis through overproduction of reactive oxygen species, regarded as an important contributor to liver damage. Grape seed-derived procyanidin (GSDP) has been reported to be an effective antioxidant, but whether and, if any, how GSDP can attenuate GLY-induced liver injury via inhibiting ferroptosis is unclear. PURPOSE: The current study aimed to investigate the hepato-protective effects and possible mechanisms of GSDP. METHODS: GLY-induced liver damage mice model was established to explore the hepatoprotective roles of GSPE in vivo. Subsequently, bioinformatics methodology was used to predict the key pathways and factors related to the action targets of GSPE against hepatocyte ferroptosis. Finally, we explored the roles of nuclear factor E2 related factor 2 (Nrf2) and fibroblast growth factor 21 (FGF21) in blunting GLY-induced liver damage via suppressing ferroptosis in vitro. RESULTS: GSDP exerts hepato-protective effects in vivo and in vitro through reduced oxidative stress and inhibited ferroptosis, which was related to the activation of Nrf2. Bioinformatics analysis showed an interaction between Nrf2 and FGF21. Furthermore, Nrf2 inhibition reduced FGF21 expression in the mRNA and protein levels. Fgf21 knockdown suppressed Nrf2 expression level, but recombinant FGF21 protein increased Nrf2 expression and promoted Nrf2 translocation into nucleus, suggesting a crosstalk between Nrf2 and FGF21. Intriguingly, the decreased levels of Nrf2 and FGF21 compromised the protective roles of GSDP against GLY-induced hepatocyte ferroptosis. CONCLUSION: These findings suggest that GSDP attenuates GLY-caused hepatocyte ferroptosis via enhancing the interplay between Nrf2 and FGF21. Thus, GSDP may be a promising natural compound to antagonize ferroptosis-related damage.

Exploring separation patterns and mechanisms of proanthocyanidins in grape seeds and pomace with diverse molecular weights, compositions, and structures.

The function of proanthocyanidins (PAs) relies on their structure and requires high-purity PAs. Though Sephadex LH-20 gel permeation chromatography (GPC) is expected to separate PAs based on structure, its usage rules and mechanisms remain unclear. This study delves into the PAs separation patterns on Sephadex LH-20, first confirming the purification mechanisms of PAs with various mean degrees of polymerization (DP) using the adsorption kinetic model. The study found that an increase in the molecular weight or mean DP of PAs results in decreased polarity, reduced hydrogen bonding actions, and intensified hydrophobic effect, causing delayed extraction of PAs on Sephadex LH-20, with galloylated PA as an exception, which was extracted first despite its high DP. Additionally, the principles for separating specific composition, such as monomers, dimers, etc., were evaluated. The study sheds light on enhancing the purification efficiency of PAs, thus advancing the precise separation technology of diverse proanthocyanidins.