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.

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.

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.

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.

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.

Procyanidin alleviates ferroptosis and inflammation of LPS-induced RAW264.7 cell via the Nrf2/HO-1 pathway.

Inflammation is a common occurrence in many medical conditions and is a natural defense mechanism of the human body. Ferroptosis, an iron-dependent form of cell death related to lipid peroxide build-up, has been found to be involved in inflammation. The anti-inflammatory effects of procyanidin, however, are not yet fully understood. Through network pharmacology and bioinformatics analysis, it was suggested that procyanidin could modulate ferroptosis and cause anti-inflammatory effects on RAW264.7 cells. This was further evidenced through molecular docking, molecular dynamics, and in vitro experiments. The results indicated that procyanidin could diminish inflammation in LPS-induced RAW264.7 cells by regulating ferroptosis via the Nrf2/HO-1/Keap-1 pathway. In conclusion, procyanidin supplementation might be an effective way to reduce inflammation by decreasing the release of inflammatory cytokines and suppressing ferroptosis.

A Comparative Analysis of Phytochemicals, Metal Ions, Volatile Metabolites in Heart Wood, Stem Bark and Leaves of Salix alba L. along with in Vitro Antioxidant, Antacid, Antimicrobial Activities for Sake of Environment Conservation by Substitution of Stem Bark With Leaf.

The genus of Salix is used in food, medicine and nutraceuticals, and standardized by using the single marker compound Salicin only. Stem bark is the official part used for the preparation of various drugs, nutraceuticals and food products, which may lead to overexploitation and damage of tree. There is need to search substitution of the stem bark with leaf of Salix alba L. (SA), which is yet not reported. Comparative phytochemicals viz. Salicin, Procyanidin B1 and Catechin were quantified in the various parts of SA viz. heart wood (SA-HW), stem bark (SA-SB) and leaves (SA-L) of Salix alba L.by using newly developed HPLC method. It was observed that SA-HW and SA-L contained far better amount of Salicin, Procyanidin B and Catechin as compared to SA-SB (SA-HW~SA-L≫SA-SB). Essential and toxic metal ions of all three parts were analysed using newly developed ICP-OES method, where SA-L were founded as a rich source of micronutrients and essential metal ions as compared to SA-SB and SA-HW. GC-MS analysis has shown the presence of fatty acids and volatile compounds. The observed TPC and TFC values for all three parts were ranged from 2.69 to 32.30 mg GAE/g of wt. and 37.57 to 220.76 mg QCE/g of wt. respectively. In DPPH assay the IC50 values of SA-SB, SA-HW, and SA-L were 1.09 (±0.02), 5.42 (±0.08), and 8.82 (±0.10) mg/mL, respectively. The order of antibacterial activities against E. coli, S. aureus, P. aeruginosa, and B. subtilis strains was SA-L>SA-HW>SA-SB with strong antibacterial activities against S. aureus, and B. subtilis strains. The antacid activities order was SA-L>SA-SB>SA-HW. The leaves of SA have shown significant source of nutrients, phytochemicals and medicinal properties than SA-HW and SA-SB. The leaves of SA may be considered as substitute of stem bark to save the environment or to avoid over exploitation, but after the complete pharmacological and toxicological studies.

Effects of grape seed procyanidins on antioxidant function, barrier function, microbial community, and metabolites of cecum in geese.

The gut is the first line of defense for body health and is essential to the overall health of geese. Grape seed procyanidins (GSPs) are proverbial for their antioxidant, anti-inflammatory, and microflora-regulating capabilities. This study aimed to inquire into the influences of dietary GSPs on the intestinal antioxidant function, barrier function, microflora, and metabolites of geese based on 16S rRNA sequencing and metabolomics. In total, 240 twenty-one-day-old Sichuan white geese were randomly divided into 4 groups, each of which was supplied with 1 of 4 diets: basal diet or a basal diet supplemented with 50, 100, or 150 mg/kg GSPs. Diets supplemented with GSPs at different concentrations significantly increased the total antioxidant capacity and superoxide dismutase activity in cecal mucosa (P < 0.001). Dietary supplementation with 50 or 100 mg/kg GSPs significantly increased catalase activity (P < 0.001). The serum diamine oxidase, D-lactic acid, and endotoxin concentrations were decreased by GSP supplementation in the goose diet. Dietary GSP supplementation increased microbial richness and diversity, enhanced the relative abundance of Firmicutes, and decreased that of Bacteroidetes in the cecum. Diets supplemented with 50 or 100 mg/kg GSPs enriched Eubacterium coprostanoligenes and Faecalibacterium. Dietary GSPs substantially raised the acetic and propionic acid concentrations in the cecum. The butyric acid concentration increased when the GSP dosage was 50 or 100 mg/kg. Additionally, dietary GSPs increased the levels of metabolites that belong to lipids and lipid-like molecules or organic acids and derivatives. Dietary GSP supplementation at 100 or 150 mg/kg reduced the levels of spermine (a source of cytotoxic metabolites) and N-acetylputrescine, which promotes in-vivo inflammation. In conclusion, dietary supplementation with GSPs was beneficial to gut health in geese. Dietary GSPs improved antioxidant activity; protected intestinal barrier integrity; increased the abundance and diversity of cecal microflora; promoted the proliferation of some beneficial bacteria; increased the production of acetic, propionic, and butyric acids in the cecum; and downregulated metabolites associated with cytotoxicity and inflammation. These results offer a strategy for promoting intestinal health in farmed geese.

Apple Pomace Compositional Data Highlighting the Proportional Contribution of Polymeric Procyanidins.

Recent years have seen an increase in research focusing on the amelioration of apple pomace waste for use in the food and nutraceutical industries. Much of this work has concentrated on the characterisation of the polyphenol composition of apple pomace materials to determine their role in conferring nutritional and health benefits. Although apples contain substantial quantities of polymeric procyanidins (condensed tannins), this class of compounds has received limited attention in apple research. This study quantified the polymeric procyanidins in apple pomace extracts using a rapid, methyl-cellulose precipitation (MCP) approach for the first time. In addition, a non-targeted metabolomics approach was applied to determine the most abundant phenolic classes present. Polymeric procyanidins were found to be the most abundant type of polyphenol in apple pomace extracts and were generally oligomeric in nature. Multivariate statistical analysis revealed that the ferric-reducing antioxidant power (FRAP) was most strongly correlated with the polymeric procyanidin concentration. Noting that polymeric procyanidins may not cross the cell layer to exert antioxidant activity in vivo, their presence in apple pomace extracts may therefore overestimate the FRAP. This work highlights the importance of polymeric procyanidins in the phenolic diversity of apple pomaces, and it is proposed that in future studies, rapid MCP assays may be used for their quantification.

Mechanism of Procyanidin B2 in the Treatment of Chronic Myeloid Leukemia Based on Integrating Network Pharmacology and Molecular Docking.

OBJECTIVE: To study the pharmacological mechanism of procyanidin B2 (PCB2) on chronic myeloid leukemia (CML) by integrating network pharmacological methods systematically. METHODS: Firstly, the potential target genes of PCB2 were predicted by the pharmacological database and analysis platform (TCMSP and Pharmmapper). Meanwhile, the relevant target genes of CML were collected from GeneCards and DisGene. Pooled data were collected to screen for common target genes. Furthermore, the above intersection genes were imported into the String website to construct a protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. Besides, molecular docking was performed to verify the possible binding conformation between PCB2 and candidate targets. Finally, MTT and RT-PCR experiments of K562 cells were performed to verify the above results of network pharmacology. RESULTS: A total of 229 PCB2 target genes were retrieved, among which 186 target genes had interaction with CML. The pharmacological effects of PCB2 on CML were related to some important oncogenes and signaling pathways. The top ten core targets predicted by Network Analysis were as follows: AKT1, EGFR, ESR1, CASP3, SRC, VEGFA, HIF1A, ERBB2, MTOR, and IGF1. Molecular docking studies confirmed that hydrogen bonding was the main interaction force of PCB2 binding targets. According to the molecular docking score, the following three target proteins were most likely to bind to PCB2: VEGFA (-5.5 kcal/mol), SRC (-5.1 kcal/mol), and EGFR (-4.6 kcal/mol). After treatment of PCB2 for 24h, mRNA expression levels of VEGFA and HIF1A decreased significantly in K562 cells. CONCLUSION: Through integrating network pharmacology combined with molecular docking, the study revealed the potential mechanism of PCB2 anti-chronic myeloid leukemia.

Procyanidin B2 regulates the Sirt1/Nrf2 signaling pathway to improve random-pattern skin flap survival.

Random-pattern skin flaps have been widely used in the reconstruction of damaged tissues. Ischemia-reperfusion injury occurring in the distal regions of the flap is a common issue, which often leads to flap necrosis and restricts its clinical applications. Procyanidin B2 (PB2), a naturally occurring flavonoid in large quantities in various fruits, has been demonstrated to exhibit several significant pharmacological properties. However, the effect of PB2 on flap viability is not clearly known. Here, using Western blot analysis, immunohistochemistry, and immunofluorescence staining, we observed that PB2 significantly reduced oxidative stress and inflammation and enhanced angiogenesis. Mechanically, we provided evidence for the first time that the beneficial effects of PB2 occur through the activation of the Sirt1/Nrf2 signaling pathway. Moreover, co-administration of PB2 and EX527, a selective inhibitor of Sirt1, resulted in down-regulation of the expression of Sirt1, Nrf2, and downstream antioxidants. In summary, our study showed that PB2 might be a novel therapeutic strategy for improving the survival of random-pattern skin flaps.

Characterization and bioactivity of A-type procyanidins from litchi fruitlets at different degrees of development.

Characterization and bioactivity of A-type procyanidins was investigated in litchi fruitlet (LF) at different stages and mature pericarp (MP) of 5 litchi cultivars. The content of total phenols in LFs was higher than that of MP and showed good antioxidant activity. Eleven procyanidins were identified in samples, including procyanidin A2, procyanidin A4, and 1 dimer, 2 trimers, and 1 tetramer of A-type procyanidin. Also, A-type procyanidin could stably exist in LFs stage, but declined substantially after maturity, which was about 1.45 - 3.56 times than mature pericarp. In addition, the second stage of LFs showed strong anti-inflammatory and anti-proliferative activities, in which monomer and A-type procyanidin trimers in LFs were significantly correlated with antioxidant (r > 0.72; p < 0.01) and anti-inflammatory (r = 0.53; p < 0.05) activities, respectively. Therefore, litchi in LF stage could be a good source of A-type oligomer procyanidins which had good application value.

Investigation of the chemical composition of antibacterial Psidium guajava extract and partitions against foodborne pathogens.

P. guajava was partitioned into aqueous and ethyl acetate fractions and studied for its antibacterial chemical constituents. The minimum inhibitory concentrations of the aqueous and ethyl acetate partitions against Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus were found to be 0.75, 0.75, 0.15, 0.5, 0.5, and 0.125%, respectively. Using LC-MS-based chemical fingerprinting, auto MS/MS fragmentation and bioactive molecular networking, 18 compounds of interest were detected. The top 10 bioactive compounds and eight additional non-bioactive compounds known to be found in P. guajava are highlighted. We report five compounds to be identified in P. guajava for the first time. Studies have indicated P. guajava to be a plant source of antibacterial compounds that could be useful in the food industry to prevent foodborne illnesses outbreaks, reduce food spoilage, and satisfy consumer demands for less synthetic chemical usage in the food industry.

Phenolic Profile and Antioxidant Properties in Extracts of Developing Açaí (Euterpe oleracea Mart.) Seeds.

We investigated changes in the phenolic profile and antioxidant properties in the extracts of developing seeds of açaí (Euterpe oleracea). Four developmental stages were evaluated, with earlier stages displaying higher antioxidant activity and polyphenols content, while mass spectrometry analysis identified procyanidins (PCs) as the major components of the extracts in all stages. B-type PCs varied from dimers to decamers, with A-type linkages in a smaller number. Extracted PCs decreased in average length from 20.5 to 10.1 along seed development. PC composition indicated that (-)-epicatechin corresponded to over 95% of extension units in all stages, while (+)-catechin presence as the starter unit increased from 42 to 78.8% during seed development. This variation was correlated to the abundance of key enzymes for PC biosynthesis during seed development. This study is the first to report PC content and composition variations during açaí seed development, which can contribute to studies on the plant's physiology and biotechnological applications.

Coordination of AMPK and YAP by Spatholobi Caulis and Procyanidin B2 Provides Antioxidant Effects In Vitro and In Vivo.

The liver is vulnerable to oxidative attacks from heavy metals, such as iron, as well as some drugs, including acetaminophen. It has been shown that enhanced oxidative stress in the liver leads to excessive ROS production and mitochondrial dysfunction, resulting in organ injury. The beneficial effects of Spatholobi Caulis (SC), a natural herbal medicine, include treating ischemic stroke, inhibiting tumor cell invasion, pro-angiogenic activities, and anti-inflammatory properties. Scientific studies on its effects against hepatotoxic reagents (e.g., iron and acetaminophen), as well as their underlying mechanisms, are insufficient. This study examined the antioxidant effects and mechanisms of SC in vitro and in vivo. In cells, the proinflammatory mediator, arachidonic acid (AA), plus iron, significantly induced an increase in ROS generation, the damage in mitochondrial membrane potential, and the resulting apoptosis, which were markedly blocked by SC. More importantly, SC affected the activation of AMP-activated protein kinase (AMPK)-related proteins, which were vital to regulating oxidative stress in cells. In addition, SC mediated the expression of Yes-associated protein (YAP)-related proteins. Among the active compounds in SC, the procyanidin B2, but not liquiritigenin, daidzein, and genistein, significantly inhibited the cytotoxicity induced by AA + iron, and activated the LKB1-AMPK pathway. In mice, the oral administration of SC alleviated the elevations of ALT and histological changes by the acetaminophen-induced liver injury. These results reveal the potential of SC and a key bioactive component, procyanidin B2, as antioxidant candidates for hepatoprotection.

Quantification and purification of procyanidin B1 from food byproducts.

The flavan-3-ols of 10 primarily plant food byproducts, including Muscat Hamburg grape seed, hawthorn sarcocarp, litchi pericarp, cocoa bean, peanut skin, lotus seedpod, Xinyang Maojian green tea, Cinnamomi cortex, Sargentodoxa cuneata stem, and Cyperus esculentus, leaves were analyzed. Ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry was used for the analysis. Cyperus esculentus leaves contained a high amount of procyanidin B1 (198.9 mg/100 g), second only to Muscat Hamburg grape seed (292.9 mg/100 g). Unlike grape seed that contained several procyanidin B isomers with very similar retention times, C. esculentus leaves contained primarily procyanidin B1 with few isomers. Procyanidin B1 was enriched in the ethyl acetate fraction of a 70% methanol extract of C. esculentus leaves and purified at 95% purity by two runs of open column chromatography. Direct chromatography of the plant extract on octadecylsilane and Sephadex LH20 open columns improved the yield of the resultant leaf procyanidin B1 (95% purity) to 0.21‰. The present research demonstrated that the leaves of C. esculentus, byproducts of tigernut, are ideal plant sources for isolating and providing high-purity procyanidin B1. PRACTICAL APPLICATION: Procyanidin B1 has a broad range of health benefits. Cyperus esculentus is cultivated in many countries with nearly 6190 square hectares (hm2 ) in the Spanish Mediterranean region in 2020-2021 and over 16,700 hm2 in China in recent years, primarily for its tubers. The byproducts, the leaves of C. esculentus, contain high levels of procyanidin B1, with few isomers that interfere with its isolation and purification. Thus, the leaves of this plant provide a viable source for preparing high-purity procyanidin B1.

Biocompatible Films of Collagen-Procyanidin for Wound Healing Applications.

The study investigated the effect of polyphenols present in Cassia auriculata (CA) leaves in enhancing the stability of the collagen protein and the wound healing potential of collagen films. The crude ethanol extract of CA was analyzed for the presence of phytochemicals and purified by column chromatography using solvents with increasing polarity. The ethanol eluted active fractions (EEAF) that precipitated gelatin was characterized using HP-TLC, FTIR spectroscopy, ESI-FT-MS/MS, and 1H NMR spectroscopy. The active compound was identified to be procyanidin B belonging to the proanthocyanidins group. The wound healing property of EEAF and collagen type I extracted from Clarias batrachus fish skin and the bovine tendon was assessed by in vitro scratch assay on L929 mice fibroblast cell lines. The EEAF-treated collagen coating enhanced in vitro wound closure in comparison with the uncoated dish. It was observed that EEAF treatment improved the physical strength of collagen films. The in vivo wound healing of the EEAF-treated collagen film was examined in male Wister rats and the wound site tissues were assessed. In vivo wound examination showed enhanced healing with EEAF incorporated collagen films. Comparatively, the EEAF-treated bovine tendon collagen films showed improved physical properties and better wound healing property than fish collagen films.

Ebola Entry Inhibitors Discovered from Maesa perlarius.

Ebola virus disease (EVD), a disease caused by infection with Ebola virus (EBOV), is characterized by hemorrhagic fever and a high case fatality rate. With limited options for the treatment of EVD, anti-Ebola viral therapeutics need to be urgently developed. In this study, over 500 extracts of medicinal plants collected in the Lingnan region were tested against infection with Ebola-virus-pseudotyped particles (EBOVpp), leading to the discovery of Maesa perlarius as an anti-EBOV plant lead. The methanol extract (MPBE) of the stems of this plant showed an inhibitory effect against EBOVpp, with an IC50 value of 0.52 µg/mL, which was confirmed by testing the extract against infectious EBOV in a biosafety level 4 laboratory. The bioassay-guided fractionation of MPBE resulted in three proanthocyanidins (procyanidin B2 (1), procyanidin C1 (2), and epicatechin-(4ß→8)-epicatechin-(4ß→8)-epicatechin-(4ß→8)-epicatechin (3)), along with two flavan-3-ols ((+)-catechin (4) and (-)-epicatechin (5)). The IC50 values of the compounds against pseudovirion-bearing EBOV-GP ranged from 0.83 to 36.0 µM, with 1 as the most potent inhibitor. The anti-EBOV activities of five synthetic derivatives together with six commercially available analogues, including EGCG ((-)-epigallocatechin-3-O-gallate (8)), were further investigated. Molecular docking analysis and binding affinity measurement suggested the EBOV glycoprotein could be a potential molecular target for 1 and its related compounds.

Time-of-Day Circadian Modulation of Grape-Seed Procyanidin Extract (GSPE) in Hepatic Mitochondrial Dynamics in Cafeteria-Diet-Induced Obese Rats.

Major susceptibility to alterations in liver function (e.g., hepatic steatosis) in a prone environment due to circadian misalignments represents a common consequence of recent sociobiological behavior (i.e., food excess and sleep deprivation). Natural compounds and, more concisely, polyphenols have been shown as an interesting tool for fighting against metabolic syndrome and related consequences. Furthermore, mitochondria have been identified as an important target for mediation of the health effects of these compounds. Additionally, mitochondrial function and dynamics are strongly regulated in a circadian way. Thus, we wondered whether some of the beneficial effects of grape-seed procyanidin extract (GSPE) on metabolic syndrome could be mediated by a circadian modulation of mitochondrial homeostasis. For this purpose, rats were subjected to "standard", "cafeteria" and "cafeteria diet + GSPE" treatments (n = 4/group) for 9 weeks (the last 4 weeks, GSPE/vehicle) of treatment, administering the extract/vehicle at diurnal or nocturnal times (ZT0 or ZT12). For circadian assessment, one hour after turning the light on (ZT1), animals were sacrificed every 6 h (ZT1, ZT7, ZT13 and ZT19). Interestingly, GSPE was able to restore the rhythm on clock hepatic genes (Bmal1, Per2, Cry1, Rorα), as this correction was more evident in nocturnal treatment. Additionally, during nocturnal treatment, an increase in hepatic fusion genes and a decrease in fission genes were observed. Regarding mitochondrial complex activity, there was a strong effect of cafeteria diet at nearly all ZTs, and GSPE was able to restore activity at discrete ZTs, mainly in the diurnal treatment (ZT0). Furthermore, a differential behavior was observed in tricarboxylic acid (TCA) metabolites between GSPE diurnal and nocturnal administration times. Therefore, GSPE may serve as a nutritional preventive strategy in the recovery of hepatic-related metabolic disease by modulating mitochondrial dynamics, which is concomitant to the restoration of the hepatic circadian machinery.

Black tea bioactives as inhibitors of multiple targets of SARS-CoV-2 (3CLpro, PLpro and RdRp): a virtual screening and molecular dynamic simulation study.

The global pandemic due to the novel Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has taken more than a million lives. Lack of definitive vaccine/drugs against this highly contagious virus has accelerated exploratory research on novel natural and synthetic inhibitors. Tea is a rich source of bioactives and known to have antiviral properties. In this study, an in silico strategy involving ADMET property screening, receptor-ligand docking and molecular dynamic (MD) simulation was employed to screen potential tea bio-active inhibitors against three selected targets (RdRp, 3CLpro and PLpro) of SARS-CoV-2. Among the 70 tea bioactives screened, theaflavin 3,3'-di-gallate (TF3), Procyanidin B2 and Theaflavin 3-gallate (TF2a) exhibited highest binding affinities towards RdRp, 3CLpro/Mpro and PLpro targets of SARS-CoV-2 with low docking scores of -14.92, -11.68 and -10.90 kcal/mol, respectively. All of them showed a substantial number of hydrogen bonds along with other interactions in and around the active sites. Interestingly, the top bioactives in our study showed higher binding affinities compared with known antiviral drugs. Further, the top protein-ligand complexes showed less conformational changes during binding when subjected to MD simulation for 100 nanoseconds. The MMPBSA results revealed that RdRp-TF3, 3CLpro-Procyanidin B2 and PLpro-TF2a complexes were stable with binding free energies of -93.59 ± 43.97, -139.78 ± 16.51 and -96.88 ± 25.39 kJ/mol, respectively. Our results suggest that theaflavin 3,3'-digallate, Theaflavin 3-gallate and Procyanidin B2 found in black tea have the potential to act as inhibitors for selected targets of SARS-CoV-2 and can be considered as drug candidates in future studies against COVID-19.