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This paper investigates the impact of cognitive load on the formation and maintenance of cooperation within a public goods game experiment featuring a punishment option. By integrating the experimental designs of prior studies and manipulating cognitive load through the memorization of numbers with varying digits, we reveal that high cognitive load accelerates the breakdown of cooperation, irrespective of the presence of a punishment system. Furthermore, under high cognitive load, participants are more likely to engage in antisocial punishment, while the punishment of free riders remains unaffected. These findings suggest that increased cognitive load depletes the cognitive resources needed for deliberative decision-making, leading to a higher propensity for antisocial punishment. Our study contributes to the literature by demonstrating the significant influence of cognitive load on cooperative behavior and providing new insights into the causes of antisocial punishment. [ABSTRACT FROM AUTHOR] more...

Infections caused by Candida species increased, as well as species resistant to the most conventional antimicrobials. Thus, the search for new natural sources of antimicrobials without adverse effects also increased. In this case, Astronium urundeuva Engl., a medicinal plant with several pharmacological activities, including antifungal activity, emerges as a source of antifungal compounds. Here, we evaluated the antifungal activity of A. urundeuva and its derivatives free or loaded into a nanostructured lipid system and combination studies against Candida species. A. urundeuva component's purification and identification were performed through chromatographic and spectroscopic techniques, respectively. The major components identified were gallic acid (1), methyl gallate (2), ethyl gallate (3), and 1,2,3,4,6-penta-O-galoyl-β-D-glucose (PGG) (4). A. urundeuva extract, its aqueous fraction, and PGG (4) exhibited the same MIC values between 0.2 and 62.5 µg/mL against Candida species being classified as significant activity, while the amphotericin B MIC was 0.1–1.2 µg/mL. Combination assay demonstrated that may occur synergism (0.37) between gallic acid (1) x methyl gallate (2). Thus, the results demonstrated as PGG (4) much as the gallic acid (1) x methyl gallate (2) combined might be the main responsible for the antifungal activity against Candida species, mainly Candida glabrata ATCC 2001 and that the tested nanostructured system maintained the antifungal activity. Through the antifungal activity of the extract and purified compounds, the extract may be employed in the development of antifungal herbal medicine, because its purification process is simple and greener than pure compounds. [ABSTRACT FROM AUTHOR] more...

Combining phytochemicals with chemotherapeutic drugs has demonstrated the potential to surmount drug resistance. In this paper, we explore the efficacy of pentagalloyl glucose (PGG) in modulating P-gp and reversing multidrug resistance (MDR) in drug-resistant leukemic cells (K562/ADR). The cytotoxicity of PGG was evaluated using a CCK-8 assay, and cell apoptosis was assessed using flow cytometry. Western blotting was used to analyze protein expression levels. P-glycoprotein (P-gp) activity was evaluated by monitoring the kinetics of P-gp-mediated efflux of pirarubicin (THP). Finally, molecular docking, molecular dynamics simulation, and molecular mechanics with generalized Born and surface area solvation (MM-GBSA) calculation were conducted to investigate drug–protein interactions. We found that PGG selectively induced cytotoxicity in K562/ADR cells and enhanced sensitivity to doxorubicin (DOX), indicating its potential as a reversal agent. PGG reduced the expression of P-gp and its gene transcript levels. Additionally, PGG inhibited P-gp-mediated efflux and increased intracellular drug accumulation in drug-resistant cells. Molecular dynamics simulations and MM-GBSA calculation provided insights into the binding affinity of PGG to P-gp, suggesting that PGG binds tightly to both the substrate and the ATP binding sites of P-gp. These findings support the potential of PGG to target P-gp, reverse drug resistance, and enhance the efficacy of anticancer therapies. [ABSTRACT FROM AUTHOR] more...

ABSTRACTInhibition of cluster of differentiation 44 (CD44), a pancreatic cancer stem cell (CSC) marker, is a potential treatment for pancreatic ductal adenocarcinoma (PDAC). In this study, we evaluated the effect of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), a gallotannin contained in various medicinal plants, on CD44 standard (CD44s) and CD44 variant 3 (CD44v3) in Mia-PaCa-2, human pancreatic cancer cells and explored the underlying mechanisms. PGG showed cytotoxic effects and inhibited the proliferation of Mia-PaCa-2 cells. It also inhibited clonogenic activity, adhesion to fibronectin, and cell migration, which are characteristics of CSCs. PGG inhibited the expression of CD44s and CD44v3 by inducing the phosphorylation of p53 and suppressing NF-κB and Foxo3. Inhibition of Foxo3 induces CD44v3 ubiquitination. Indeed, PGG increased proteasome activity and promoted CD44v3 ubiquitination. PGG downregulated the CSC regulatory factors Nanog, Oct-4, and Sox-2, which act downstream of CD44v3 signaling. These data indicate that PGG may have therapeutic effects in pancreatic cancer mediated by inhibition of CSC markers. more...

Inhibition of cluster of differentiation 44 (CD44), a pancreatic cancer stem cell (CSC) marker, is a potential treatment for pancreatic ductal adenocarcinoma (PDAC). In this study, we evaluated the effect of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), a gallotannin contained in various medicinal plants, on CD44 standard (CD44s) and CD44 variant 3 (CD44v3) in Mia-PaCa-2, human pancreatic cancer cells and explored the underlying mechanisms. PGG showed cytotoxic effects and inhibited the proliferation of Mia-PaCa-2 cells. It also inhibited clonogenic activity, adhesion to fibronectin, and cell migration, which are characteristics of CSCs. PGG inhibited the expression of CD44s and CD44v3 by inducing the phosphorylation of p53 and suppressing NF-κB and Foxo3. Inhibition of Foxo3 induces CD44v3 ubiquitination. Indeed, PGG increased proteasome activity and promoted CD44v3 ubiquitination. PGG downregulated the CSC regulatory factors Nanog, Oct-4, and Sox-2, which act downstream of CD44v3 signaling. These data indicate that PGG may have therapeutic effects in pancreatic cancer mediated by inhibition of CSC markers. [ABSTRACT FROM AUTHOR] more...

Sanctioning institutions widely exist in human society. Although these institutions play an important role in the management of social affairs, sanctions are often seen to be costly in terms of both time and money. To enable sanctioning institutions to develop effective sanctions, we propose a negative feedback punishment approach for these institutions that combines the feedback control principle and the negative correlation principle. In the negative feedback punishment approach, the punishment intensity imposed on the group is negatively correlated with the current group cooperation proportion. Through evolutionary simulation and theoretical analysis, we found that the negative feedback punishment approach facilitates more stable, time-saving and low-cost performance by sanctioning institutions than other punishment methods. This work offers a feasible solution for sanctioning institutions to solve social dilemmas and provides a possible theoretical starting point for investigating effective pool punishment measures. [ABSTRACT FROM AUTHOR] more...

Herein, the apoptotic mechanism of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) was examined in cisplatin-resistant lung cancer cells. PGG significantly reduced viability; increased sub-G1 accumulation and the number of terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL)-positive cells; induced the cleavage of poly (ADP-ribose) polymerase (PARP), caspases (8,9,3,7), B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN); and attenuated the expression of p-AKT, X-linked inhibitor of apoptosis protein (XIAP), Bcl-2, Bcl-xL and survivin in A549/cisplatin-resistant (CR) and H460/CR cells. Notably, PGG activated p53, p-checkpoint kinase 2 (CHK2) and p-H2A histone family member X (p-H2AX), with increased levels of DNA damage (DSBs) evaluated by highly expressed pH2AX and DNA fragmentation registered on comet assay, while p53 knockdown reduced the ability of PGG to reduce viability and cleave caspase 3 and PARP in A549/CR and H460/CR cells. Additionally, PGG treatment suppressed the growth of H460/CR cells in Balb/c athymic nude mice with increased caspase 3 expression compared with the cisplatin group. Overall, PGG induces apoptosis in cisplatin-resistant lung cancer cells via the upregulation of DNA damage proteins such as γ-H2AX, pCHK2 and p53. [ABSTRACT FROM AUTHOR] more...

The coronavirus disease (COVID-19) pandemic, resulting from human-to-human transmission of a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has led to a global health crisis. Given that the 3 chymotrypsin-like protease (3CLpro) of SARS-CoV-2 plays an indispensable role in viral polyprotein processing, its successful inhibition halts viral replication and thus constrains virus spread. Therefore, developing an effective SARS-CoV-2 3CLpro inhibitor to treat COVID-19 is imperative. A fluorescence resonance energy transfer (FRET)-based method was used to assess the proteolytic activity of SARS-CoV-2 3CLpro using intramolecularly quenched fluorogenic peptide substrates corresponding to the cleavage sequence of SARS-CoV-2 3CLpro. Molecular modeling with GEMDOCK was used to simulate the molecular interactions between drugs and the binding pocket of SARS-CoV-2 3CLpro. This study revealed that the V max of SARS-CoV-2 3CLpro was about 2-fold higher than that of SARS-CoV 3CLpro. Interestingly, the proteolytic activity of SARS-CoV-2 3CLpro is slightly more efficient than that of SARS-CoV 3CLpro. Meanwhile, natural compounds PGG and EGCG showed remarkable inhibitory activity against SARS-CoV-2 3CLpro than against SARS-CoV 3CLpro. In molecular docking, PGG and EGCG strongly interacted with the substrate binding pocket of SARS-CoV-2 3CLpro, forming hydrogen bonds with multiple residues, including the catalytic residues C145 and H41. The activities of PGG and EGCG against SARS-CoV-2 3CLpro demonstrate their inhibition of viral protease activity and highlight their therapeutic potentials for treating SARS-CoV-2 infection. [Display omitted] • An effective SARS-CoV-2 3CLpro inhibitor is imperative for COVID-19 treatment. • The V max of SARS-CoV-2 3CLpro was about 2-fold higher than that of SARS-CoV 3CLpro. • PGG and EGCG show potent inhibitory activity against SARS-CoV-2 3CLpro. • PGG and EGCG strongly interact with the catalytic sites of SARS-CoV-2 3CLpro. • PGG and EGCG possess therapeutic potentials for treating SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR] more...

1,2,3,4,6-Penta-O-Galloyl-β-d-Glucose (PGG) is a hydrolysable tannin that belongs to the group of gallotannins but also participates in the formation of ellagitannins. PGG is composed of five galloyl groups with a glucose at its core and has structural characteristics that confer a high biological power. In this paper, we describe the chemistry of PGG, which is analyzed from a critical point regarding the types of synthesis, new sources of production from plants and by-products, highlighting the PGG obtaining, and its main functional properties recently reported in scientific literature. PGG has attracted attention because of its therapeutic potential and has shown functional properties as antimicrobial, anti-inflammatory, anti-carcinogenic, antidiabetic and antioxidant. Bioconversion from tannic acid can be potentialized with the use of biotechnological techniques. PGG can be obtained from natural sources as by-products. Research should continue to obtain pure molecules, in adequate quantity and with great biological activity. more...

Public good games are a metaphor for modeling cooperative behavior in groups in the presence of incentives to free ride. In the model presented here agents play a public good game with their neighbors in a social network structure. Agents' decision rules in our model are inspired by elementary learning observed in laboratory and online behavioral experiments involving human participants with the same amount of information, i.e., when individuals only know their own current contribution and their own cumulated payoff. In addition, agents in the model are allowed to severe links with groups in which their payoff is lower and create links to a new randomly chosen group. Reinforcing the results obtained in network scenarios where agents play Prisoner's Dilemma games, we show that thanks to this relinking possibility, the whole system reaches higher levels of average contribution with respect to the case in which the network cannot change. Our setup opens new frameworks to be investigated, and potentially confirmed, through controlled human experiments. more...

Objective: There are various exercises for voice therapy, but current evidence is insufficient to decide the most effective training technique for each type of dysphonia. This study focused on vocal attack as one of the causes of dysphonia. Hence, vocal attack during voice therapy exercises was investigated using photoglottogram (PGG)., Methods: Eighteen healthy adult subjects (10 males and 8 females) were included in this study. The first to fifth vocal waves during natural voice, hard and soft voice onset, and semi-occluded vocal tract exercises (SOVTE: humming, tubing, and lip trill) were assessed. We also calculated the 25% vocal fold open quotient (OQ) using a PGG and compared these parameters., Results: The 25% OQ did not show any sex-related differences. In the first wave, the 25% OQ for hard attack was significantly lower than that for soft attack, tongue-out humming, and lip trill. In contrast, the 25% OQ value for soft attack was significantly higher than that for humming, 6 mm tube phonation, and lip trill. The 25% OQ values differed between SOVTE procedures; it was higher for the 13 mm tube phonation than for the 6 mm tube phonation. The 25% OQ at voice onset in the first to fifth waves differed depending on the SOVTE technique, indicating different voice onset patterns., Conclusions: These results suggest that appropriate selection of SOVTE tailored for each patient may have benefit in further voice improvement. Future research should focus on conducting a similar study on patients with dysphonia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.) more...

Our previous study showed that pentagalloylglucose (PGG), a naturally occurring hydrolyzable phenolic tannin, possesses significant anti-rabies virus (RABV) activity. In BHK-21 cells, RABV induced the overactivation of signal transducer and activator of transcription 3 (STAT3) by suppressing the expression of suppressor of cytokine signaling 3 (SOCS3). Inhibition of STAT3 by niclosamide, small interfering RNA, or exogenous expression of SOCS3 all significantly suppressed the replication of RABV. Additionally, RABV-induced upregulation of microRNA 455-5p (miR-455-5p) downregulated SOCS3 by directly binding to the 3= untranslated region (UTR) of SOCS3. Importantly, PGG effectively reversed the expression of miR-455-5p and its following SOCS3/STAT3 signaling pathway. Finally, activated STAT3 elicited the expression of interleukin-6 (IL-6), thereby contributing to RABV-associated encephalomyelitis; however, PGG restored the level of IL-6 in vitro and in vivo in a SOCS3/STAT3-dependent manner. Altogether, these data identify a new miR-455-5p/SOCS3/STAT3 signaling pathway that contributes to viral replication and IL-6 production in RABV-infected cells, with PGG exerting its antiviral effect by inhibiting the production of miR-455-5p and the activation of STAT3. [ABSTRACT FROM AUTHOR] more...

Neuroinflammation and microglial activation are two important hallmarks of neurodegenerative diseases. Continuous microglial activation may cause the release of several cytotoxic molecules, including many cytokines that are involved in the inflammatory process. Therefore, attenuating inflammation caused by activated microglia may be an approach for the therapeutic management of neurodegenerative diseases. In addition, many studies have reported that polyphenol pentagalloyl glucose (1,2,3,4,6-penta-O-galloyl-β-D-glucose; PGG) is a molecule with potent anti-inflammatory effects, such as inhibiting the release of proinflammatory cytokines. Our previous studies revealed that PGG attenuated the expression of two inflammatory cytokines (murine monocyte chemoattractant protein-5 and pro-metalloproteinase-9) in lipopolysaccharide/interferon γ-activated BV-٢ microglial cells. Additionally, PGG modulated the NF-κB and MAPK signaling pathways by altering genes and proteins, which may affect the MAPK cascade and NF-κB activation. The aim of the present study was to investigate the ability of PGG to modulate the expression of proteins released in activated BV-2 microglial cells, which may be involved in the pathological process of inflammation and neurodegeneration. Proteomic analysis of activated BV-2 cells identified 17 proteins whose expression levels were significantly downregulated by PGG, including septin-7, ataxin-2, and adenylosuccinate synthetase isozyme 2 (ADSS). These proteins were previously described as being highly expressed in neurodegenerative diseases and/or involved in the signaling pathways associated with the formation and growth of neuronal connections and the control of Alzheimer's disease pathogenesis. The inhibitory effect of PGG on ataxin-2, septin-7 and ADSS was further confirmed at the protein and transcriptional levels. Therefore, the obtained results suggest that PGG, with its potent inhibitory effects on ataxin-2, septin-7 and ADSS, may have potential use in the therapeutic management of neurodegenerative diseases. [ABSTRACT FROM AUTHOR] more...

Abstract Penta-O-galloyl-β- d -glucose (PGG) was purified and identified from Radix Paeoniae Alba by HSCCC and HPLC/ESI-MS, and its inhibitory effects on adipogenesis and TNF-α-induced inflammation were assessed in 3T3-L1 cell line. The results showed that PGG dose-dependently reduced intracellular lipids accumulation, and this involved decrease the expression levels of major adipogenic markers, PPARγ, C/EBP α, through MAPKs inhibition. This was accompanied by a reduction of lipogenic genes, ACC, FAS, and SCD-1, involved in fatty acid synthesis. Furthermore, PGG also inhibited TNF-α-induced expression of inflammatory cytokines including IL-6 and MCP-1 in the matured 3T3-L1 adipocytes. The inhibitions were likely mediated by blocking the MAPKs and NF-κB activation. These findings highlighted that PGG could serve as a potent therapeutic agent for controlling obesity and obesity-related chronic inflammation. Graphical abstract Image 1 Highlights • An efficient method for preparing PGG from Radix Paeoniae Alba by HSCCC in a single step was established for the first time. • PGG could greatly inhibit adipogenesis of 3T3-L1 cells through MAPK signaling pathway. • PGG could attenuate TNF-α-mediated adipocyte inflammation possibly through the MAPKs, and NF-κB pathways. [ABSTRACT FROM AUTHOR] more...

Graphical abstract Highlights • Self-assembly of PDMS-E grafted gelatin (PGG) is investigated in suit. • CLSM, CD, HR-TEM and XPS reveal the structure evolution of PGG at a molecular level. • Programmed self-assembly of PGG offers a superhydrophobic coating on porcine skin. • A new mechanism is proposed for developing potential application in biomaterials. Abstract Understanding the assembly mechanisms of supramolecular architectures in nature is essential for the design and synthesis of novel biomaterials. In the work, self-assembly of gelatin-mono epoxy terminated polydimethylsiloxane polymer (PGG) controlled by electrostatic and hydrophobic interactions between gelatin and sodium dodecyl sulfate (SDS) was investigated in suit. Confocal laser scanning microscopy, circular dichroism spectroscopy, high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy were conducted to reveal the structure evolution of PGG at a molecular level with the increment of SDS concentration, including micro-sized sphere, core-shell and multi-layer structure. Notably, the multi-layer structure was formed from the large contribution of antiparallel β -sheets on the boundary and new hydrophobic aggregation driven by higher monomer conversions. The delicate supramolecular architectures preliminarily present excellent anti-water, anti-contamination and anti-radiation properties in the surface of skin. The excellent self-cleaning function of PGG indicates potential application in biomaterials. [ABSTRACT FROM AUTHOR] more...

Colon cancer is the third most common malignancy in both sexes of Korea. Here, we investigated anti-colorectal cancer effects of 1,2,3,4,6-penta- O -galloyl-β- d -glucose (PGG), a gallotannin from Galla rhois, and its possible mechanisms. PGG induced cytotoxicity and decreased proliferation of colon cancer cells without affecting normal colon fibroblasts. PGG inhibited clonogenic ability and induced apoptosis in cancer cells. One of the underlying mechanisms of the anti-cancer effect exerted by PGG, was owing to the induction p53 expression, a well-known tumor suppressor, and increased in P21, the representative target gene of p53. PGG affected cell-cycle- or apoptosis-related proteins such as cyclin E, CDK2, and Bcl-2, cleaved caspase-3. Also, PGG induced caspase-3/7 activity. These data suggest that PGG exerts anti-colorectal cancer effects. [ABSTRACT FROM AUTHOR] more...

Many properties of things are heterogeneous, which promotes the reproduction and development of human society. Naturally, the reputation has heterogeneity, and the heterogeneity of reputation can effectively promote cooperation in evolutionary systems. However, how to measure the heterogeneity of reputation and reveal the evolutionary mechanisms by which it fosters cooperation is not fully understood. In this paper, a modified public goods game (PGG) model is proposed based on co-evolution mode, in which a player's reputation is measured by the number of times the player adheres to the same strategy. To better understand the influence of heterogeneous reputation on individual's decision, we propose two evolutionary mechanisms, namely the absolute mechanism and the relative mechanism based on reputation. Simulation verifies that two proposed mechanisms are easier to promote cooperation compared with the traditional PGG model, and the relative mechanism is easier to promote the evolution of cooperation than the absolute mechanism. • To measure the heterogeneity of reputation, we propose an improved PGG model. • Two heterogeneous evolutionary mechanisms are proposed based on reputation. • The relative mechanism is easier to promote cooperation than the absolute mechanism. • The strategy persistence times upper bound is related to the level of cooperation. • This work provides a new perspective to understand the heterogeneous reputation. [ABSTRACT FROM AUTHOR] more...

Multiple myeloma (MM) still remains an incurable disease, therefore discovery of novel drugs boosts the therapeutics for MM. The natural compound 1,2,3,4,6-Penta-O-galloyl-beta-D-glucopyranoside (PGG) has been shown to exhibit antitumor activities against various cancer cells. Here, we aim to evaluate antitumor effects of PGG on MM cell lines. PGG inhibited the growth of three different MM cell lines in a dose- and time-dependent manner. Cell cycle analysis revealed that PGG treatment caused cell cycle arrest in G1 phase. It also induced apoptosis which was indicated by significant increases of Annexin V positive cells, caspase 3/7 activity, and cleaved caspase 3 expression in PGG treated MM cell. Since MYC is frequently hyperactivated in MM and inhibition of MYC leads to MM cell death. We further demonstrated that PGG decreased MYC expression in protein and mRNA levels and reversed the mRNA expression of MYC target genes such as p21, p27, and cyclin D2. In addition, PGG also reduced protein expression of DEPTOR which is commonly overexpressed in MM. Unexpectedly, PGG antagonized the cytotoxic effect of bortezomib in the combination treatment. However, PGG treatment sensitized MM cells to another proteasome inhibitor MG132 induced cytotoxicity. Moreover, MYC inhibitor JQ1 enhanced the cytotoxic effect of bortezomib on MM cells. Our findings raised concerns about the combinatory use of bortezomib with particular types of chemicals. The evidence also provide useful insights into the combination of MYC and proteasome-inhibitors for MM therapy. Finally, PGG has a therapeutic potential for treatment of MM and further development is mandatory. more...

Multiple myeloma (MM) still remains an incurable disease, therefore discovery of novel drugs boosts the therapeutics for MM. The natural compound 1,2,3,4,6-Penta-Ogalloyl- beta-D-glucopyranoside (PGG) has been shown to exhibit antitumor activities against various cancer cells. Here, we aim to evaluate antitumor effects of PGG on MM cell lines. PGG inhibited the growth of three different MM cell lines in a dose- and time-dependent manner. Cell cycle analysis revealed that PGG treatment caused cell cycle arrest in G1 phase. It also induced apoptosis which was indicated by significant increases of Annexin V positive cells, caspase 3/7 activity, and cleaved caspase 3 expression in PGG treated MM cell. Since MYC is frequently hyperactivated in MM and inhibition of MYC leads to MM cell death. We further demonstrated that PGG decreased MYC expression in protein and mRNA levels and reversed the mRNA expression of MYC target genes such as p21, p27, and cyclin D2. In addition, PGG also reduced protein expression of DEPTOR which is commonly overexpressed in MM. Unexpectedly, PGG antagonized the cytotoxic effect of bortezomib in the combination treatment. However, PGG treatment sensitized MM cells to another proteasome inhibitor MG132 induced cytotoxicity. Moreover, MYC inhibitor JQ1 enhanced the cytotoxic effect of bortezomib on MM cells. Our findings raised concerns about the combinatory use of bortezomib with particular types of chemicals. The evidence also provide useful insights into the combination of MYC and proteasome-inhibitors for MM therapy. Finally, PGG has a therapeutic potential for treatment of MM and further development is mandatory. [ABSTRACT FROM AUTHOR] more...

Aim: Pentagalloylglucose (PGG), a hydrolyzable polyphenol was isolated from Phyllanthus emblica, which exhibited a strong inhibitory activity on HSV-1 infection, but its underlying mechanisms have not been completely delineated. Results/methodology: Using TEM, we first observed that PGG blocked the formation and maturation of HSV-1 capsid particles. Hence, we engaged in exploring the molecular mechanisms of PGG on the capsid assembly. At last, we found that PGG also blocked the relocalization of capsid proteins from the cytoplasm to the nucleus where the assembly took place. Conclusion: The current studies, for the first time, demonstrated acetylated microtubules were needed at this process of capsid proteins nuclear translocation. PGG also impairs herpes simplex virus type 1 infection by blocking capsid assembly. [ABSTRACT FROM AUTHOR] more...

1,2,3,4,6-Penta-O-Galloyl-β- d -Glucose (PGG) is a hydrolysable tannin that belongs to the group of gallotannins but also participates in the formation of ellagitannins. PGG is composed of five galloyl groups with a glucose at its core and has structural characteristics that confer a high biological power. In this paper, we describe the chemistry of PGG, which is analyzed from a critical point regarding the types of synthesis, new sources of production from plants and by-products, highlighting the PGG obtaining, and its main functional properties recently reported in scientific literature. PGG has attracted attention because of its therapeutic potential and has shown functional properties as antimicrobial, anti-inflammatory, anti-carcinogenic, antidiabetic and antioxidant. Bioconversion from tannic acid can be potentialized with the use of biotechnological techniques. PGG can be obtained from natural sources as by-products. Research should continue to obtain pure molecules, in adequate quantity and with great biological activity. [ABSTRACT FROM AUTHOR] more...

The compound 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), a gallotannin present in various plants such as Rhus chinensis Mill and Paeonia suffruticosa, has a broad spectrum of antiviral effects. The present study investigated its potency against infection of mice with rabies virus (RABV). Results demonstrated that PGG strongly inhibited virus titers (50-fold), viral mRNA expression (up to 90%), and protein synthesis in vitro. Importantly, we found that PGG not only suppressed viral adsorption and entry, but also directly inactivated RABV through suppression of autophagy by mediating activation of the mTOR-dependent autophagy signaling pathway. In vivo, PGG (10 mg/kg) alleviated the clinical symptoms and reduced the mortality of infected mice by 27.3%. Collectively, our results indicate that PGG has potent anti-RABV effect, and merits further investigation as an anti-RABV drug. more...

Penta-O-galloyl-β- d -glucose (PGG) was prepared from tannic acid methanolysis products based on HSCCC, and its protective effects and mechanism on the glucose-induced glycation were investigated for the first time. PGG was confirmed to exhibit strong anti-AGEs effects in bovine serum albumin (BSA)-glucose (Glu) and BSA-methylglyoxal (MGO) glycation systems. It was showed that PGG could inhibit the AGEs formation by blocking glycated intermediates (fructosamine and α-dicarbonyl compounds), eliminating radicals, and chelating metal-ions. In-depth mechanism analysis proved that PGG could prevent BSA from glycation by hindering the accumulation of amyloid fibrils, stabilizing the BSA secondary structures, and binding the partial glycation sites. Furthermore, PGG exhibited a prominent trapping capacities on the reactive intermediate MGO by generating PGG-mono-MGO adduct. This research indicated that PGG could be an effective agent to block Glu/MGO-triggered glycation and offered new insights into PGG as a functional ingredient in food materials for preventing diabetic syndrome. • Penta-O-galloyl-β- d -glucose (PGG) was prepared from tannic acid methanolysis products by HSCCC. • PGG significantly inhibited the formation of AGEs by multiple mechanisms. • PGG captured MGO by forming newly type PGG-mono-MGO adduct. [ABSTRACT FROM AUTHOR] more...

Background: Drug resistance is one of the bottlenecks of cancer chemotherapy in the clinic. Polymeric nanomedicine is one of the most promising strategies for overcoming poor chemotherapy responses due to the multidrug resistance (MDR). Methods: In this study, a new polymer-based drug delivery system, poly(Lγ-glutamylglutamine)-doxorubicin (PGG-Dox) conjugate, was studied in both drug-induced resistant human breast cancer MDA-MB-231/MDR cells and their parent human breast cancer MDA-MB-231 cells. The effect of PGG on facilitating the growth inhibition of Dox against multidrug resistant cells were investigated by evaluating the cytotoxicity of PGG-Dox conjugate, PGG/Dox unconjugated complex and free Dox on both cells. The underlying mechanisms in resistant cells were further studied via the intracellular traffic studies. Results: Both conjugated and unconjugated PGG significantly increased Dox uptake, prolonged Dox retention and reduced Dox efflux in the MDA-MB-231/MDR cells. The PGG-Dox conjugate is taken up by tumor cells mainly by pinocytosis pathway, in which PGG-Dox conjugate-containing vesicles are formed and enter the cells. Conclusions: This study indicated that both polymer-drug conjugate and unconjugated complex are promising strategies of overcoming resistance of anti-tumor drugs. [ABSTRACT FROM AUTHOR] more...

1,2,3,4,6-penta- O -galloyl-β-D-glucopyranose (PGG) is a gallotannin isolated from various plants. In a previous study, it was reported that PGG suppressed interleukin (IL)-4 induced signal pathway in B cell which is indispensable for immunoglobulin E (IgE) production. However, the suppressive effect of PGG on IgE production in allergen-sensitized mice remains unclear. Therefore, the aim of this study was to investigate the inhibitory effect of PGG on IgE production in ovalbumin (OVA)-sensitized mice. Mice orally administered PGG showed a decrease in total and OVA-specific IgE levels in serum. Oral administration of PGG strongly suppressed production of type 2 T helper (IL-4 and IL-13), type 1 T helper (IFN-γ), and pro-inflammatory cytokines (TNF-α and IL-6), but not anti-inflammatory cytokine (IL-10) from splenocytes of OVA-sensitized mice against OVA re-stimulation. A population of T regulatory (Treg) cells with immunosuppressive properties was increased in mesenteric lymph nodes and spleen of PGG-fed mice. PGG administration not only reduced expression levels of eotaxin, tissue inhibitors of metalloproteinases-1, and TNF-α, which assisted with IgE production, but also increased the expression of insulin-like growth factor binding protein-3 which inhibits IgE production. Additionally, PGG increased the levels of Treg cell-inducing factors such as IL-2, IL-10 and platelet factor-4 in serum. These data suggest that the inhibitory effect of PGG on IgE production could be partially caused by increasing a population of Treg cells in conjunction with Treg-inducing factors. [ABSTRACT FROM AUTHOR] more...

Organoid cultures may express several types of pattern-recognition receptors and in particular toll-like receptors, representing an extremely efficient and innovative system to understand how pathogen-associated molecular patterns exposure may affect the immunity, the growth, or differentiation of complex tissues. Here, we describe how to generate lung organoids from human-induced pluripotent stem cells. Three-dimensional (3D) cultures are then stimulated with different toll-like receptor ligands derived from fungi or with Aspergillus fumigatus. RNA sequencing may be performed upon organoid cultures to understand host-pathogen innate immune interactions., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.) more...

[Display omitted] • Mechanisms of the very early steps of Aβ 1-42 protofibril disassembly by PGG were studied. • The probability of β-sheet structure in Aβ 1-42 protofibril was reduced by PGG. • PGG weakened the interactions between Chain-1 and Chain-2 in Aβ 1-42 protofibril. • PGG markedly disrupted the Lys 28 -Ala 42 salt bridges network in Aβ 1-42 protofibril. Aβ peptide aggregates were the main targets to treat AD. Previous experimental study demonstrated that the 1, 2, 3, 4, 6-penta- O -galloyl-β-D-glucopyranose (PGG, containing 5 gallate moieties) dramatically destabilized the preformed Aβ fibril in vitro and in vivo. However, the mechanisms were still poorly understood. Herein, by performing molecular dynamics simulations, the detailed mechanisms of the very early steps of Aβ 1-42 pentameric protofibril disassembly by PGG were explored. It was demonstrated that the binding of PGG molecules to Aβ 1-42 pentameric protofibril disrupted the β-sheet structure, weakened the interactions between Chain-1 and Chain-2, and disturbed the Lys 28 -Ala 42 salt bridges in Aβ 1-42 pentameric protofibril. We found that the hydrophobic interactions, hydrogen bonds, pi-pi interactions and cation-pi interactions existed between PGG molecules and amino acid residues in the corner of L-shaped part (Phe 4 -Leu 17) were conducive to the disaggregation of the close interactions between Chain-1 and Chain-2. Moreover, PGG molecules disrupted the Lys 28 -Ala 42 salt bridges not only by the hydrogen bonds and cation-pi interactions with Lys 28 but also through the interactions with C-terminal hydrophobic amino acid residues. We believed that our results could provide significant insights into the mechanisms of the very early steps of Aβ 1-42 pentameric protofibril disassembly by PGG. [ABSTRACT FROM AUTHOR] more...

We study the impact of heterogeneous aspirations on the spatial public goods game (PGG) in a square lattice. An aspiration parameter u is introduced to decide who will be more probably to become the potential strategy source in structured population. Individuals are divided into two groups A(u > 0) and B(u = 0) by fraction v and 1 - v. We study how u and v affect cooperation in the PGG. For low values of u, the cooperation level monotonously increases as v increases. However, for large values of u, there exist an intermediate ≈ 0.5 for which cooperation thrives best. The influence of noise is also investigated. We find that the highest threshold of phase transition is reached at the middle value of noise. [ABSTRACT FROM AUTHOR] more...

Abstract: Astringency is an organoleptic property resulting mostly from the interaction of salivary proteins with dietary polyphenols. It is of great importance to consumers but being typically measured by sensorial panels it turns out subjective and expensive. The main goal of the present work is to develop a sensory system to estimate astringency relying on protein/polyphenol interactions. For this purpose, a model protein was immobilized on a sensory gold surface and its subsequent interaction with polyphenols was measured by Surface Plasma Resonance (SPR). α-amylase and pentagalloyl glucose (PGG) were selected as model protein and polyphenol, respectively. To ensure specific binding between these, various surface chemistries were tested. Carboxylic terminated thiol decreased the binding ability of PGG and allowed covalent attachment of α-amylase to the surface. The pH 5 was the optimal condition for α-amylase immobilization on the surface. Further studies focus on Localized SPR sensor and application to wine samples, providing objectivity when compared to a trained panel. [Copyright &y& Elsevier] more...

Abstract: Although 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) was well known to have antitumor activities in breast, prostate, kidney, liver cancers and HL-60 leukemia via regulation of caspase 3, p53, S-phase kinase-associated protein 2 (Skp2) and insulin receptor signaling, the underlying mechanism of PGG-induced apoptosis linked with reactive oxygen species (ROS) mediated c-Jun N-terminal kinase (JNK) and DAXX was never elucidated in chronic myeloid leukemia (CML) K562 cells until now. Herein PGG significantly decreased the viability of CML cell lines such as K562 and KBM-5 without hurting normal peripheral blood lymphocytes (PBLs). PGG increased the number of TUNEL-positive cells and the sub-G1 cell population as well as activated caspase cascades including caspase-8, -9 and -3 in K562 cells. Interestingly, a significant activation of JNK by PGG was observed by MULTIPLEX assay and Western blotting. Conversely, JNK inhibitor D-JNKi suppressed the cleavages of caspase 3 and PARP induced by PGG in K562 cells. Also, PGG dramatically enhanced generation of ROS and reduced the expression of death-domain-associated protein (DAXX). Of note, ROS inhibitor acetyl-l-cysteine (NAC) reversed JNK-dependent apoptosis and DAXX inhibition induced by PGG. Overall, these findings suggest that ROS-dependent JNK activation and DAXX downregulation are critically involved in PGG-induced apoptosis in K562 cells. [Copyright &y& Elsevier] more...

Abstract: Cisplatin shows limited therapeutic efficacy due to serious side effects such as nephrotoxicity and hepatotoxicity. In the present study, we demonstrate that 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) has protective effects against cisplatin-induced cytotoxicity and apoptosis in normal human primary renal epithelial cells (HRCs) while showing synergistic effect against cisplatin-induced cell death in human Caki-2 renal cancer cells. PGG significantly blocked cisplatin-mediated cytotoxicity and reduced cisplatin-induced sub-G1 accumulation in HRCs. Consistently, PGG reduced the number of apoptotic cell populations by TdT-mediated dUTP nick end labeling (TUNEL) and Live/Dead assays in cisplatin-treated HRCs. Furthermore, PGG suppressed PARP cleavage and caspase-3 activation, cytochrome c release, up-regulation of bax and p53 in cisplatin-treated HRCs. Moreover, PGG attenuated reactive oxygen species (ROS) production mediated by cisplatin treatment, suggesting that PGG prevented cisplatin-induced apoptosis by inhibiting ROS generation in HRCs. Notably, PGG significantly enhanced cytotoxicity and PARP cleavage in cisplatin-treated Caki-2 renal cancer cells. Combination Index (CI) revealed synergism between PGG and cisplatin in Caki-2 cells. Taken together, our findings suggest the dual effects of PGG as a protective supplement against cisplatin-induced toxicity in normal renal cells and a combination chemotherapeutic drug with cisplatin in renal cancer cells. [Copyright &y& Elsevier] more...

Abstract: Retention of tannins, produced by plants, could be important for managing soil organic matter and nutrient cycling. However, we know little about the comparative retention of different classes of tannins and related compounds or if soils have a maximum storage capacity for them. To address these questions, forest, and pasture loam soils, collected at 0–5 cm (surface) and 10–20 cm (subsurface), were repeatedly treated with water (Control) or solutions containing condensed and hydrolyzable tannins or related phenolic subunits (10 mg g−1 soil). Treatments included a polymeric flavonoid-based procyanidin from sorghum, catechin, tannic acid, β-1,2,3,4,6-penta-O-galloyl-d-glucose (PGG), gallic acid, and methyl gallate. After each application, soluble-C in supernatants was determined by oxidative-combustion infrared analysis and retention of treatment-carbon by soil was calculated as the difference between added and recovered soluble-C. An interaction between soil depth and treatment was evident through all applications with highest retention of both hydrophobic (PGG) and hydrophilic (procyanidin) tannins, compared to other phenolic compounds. For all treatments except gallic acid and methyl gallate, higher sorption occurred in surface soil, which contained more organic matter than subsurface soil. With each successive application, less additional treatment-C was retained by soil and the amount of C remaining in supernatants was correlated with the presence of phenolic substances. Cumulative retention by surface soil was more than 10.3, 8.5 and 6.4 mg C g−1 soil for PGG, tannic acid, and procyanidin, several times higher than the other compounds. Soluble-C extracted from treated soil, with cool water (23 °C), was 1–2 orders of magnitude greater than Control samples and highly correlated with Prussian Blue (PB) phenolics, indicating some retained treatment-C was only weakly held on the soil. The final extraction, with hot water (80 °C), removed more soluble-C, particularly from surface samples, that contained fewer PB phenolics per unit soluble-C than cool water extracts. After all extractions more than 85% of sorbed procyanidin-C was retained by samples compared to 81% of methyl gallate, 79% of PGG, 74% of tannic acid, 50% of catechin, and 40% of the gallic acid. Total C, measured in soil after all extractions, was close to expected values, confirming tannins and phenolic compounds had remained in soil and were not otherwise lost. Cation exchange capacity was increased about 30% in subsurface and forest samples by PGG, a hydrolyzable tannin, but decreased by 30% and 35% in surface and pasture soil, respectively, by its monomer, gallic acid. [Copyright &y& Elsevier] more...

Abstract: Keratinocytes, one of major cell types in the skin, can be induced by TNF-α and IFN-γ to express thymus- and activation-regulated chemokine (TARC/CCL17), which is considered to be a pivotal mediator in the inflammatory responses during the development of inflammatory skin diseases, such as atopic dermatitis (AD). In this study, we examined the effect of 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), isolated from the barks of Juglans mandshurica, on TNF-α/IFN-γ induced CCL17 expression in the human keratinocyte cell line HaCaT. Pretreatment of HaCaT cells with PGG suppressed TNF-α/IFN-γ-induced protein and mRNA expression of CCL17. PGG significantly inhibited TNF-α/IFN-γ-induced NF-κB activation as well as STAT1 activation. Furthermore, pretreatment with PGG resulted in significant reduction in expression of CXCL9, 10, and 11 in the HaCaT cells treated with IFN-γ. These results suggest that PGG may exert anti-inflammatory responses by suppressing TNF-α and/or IFN-γ-induced activation of NF-κB and STAT1 in the keratinocytes and might be a useful tool in therapy of skin inflammatory diseases. [Copyright &y& Elsevier] more...

Abstract: Some tannins, plant-derived polyphenolic compounds, can rapidly affix to soil and affect the solubility of labile soil-N but a more complete understanding of the nature and persistence of tannin-soil interactions is needed. Forest and pasture soils from two depths were treated for 1 h with cool (23 °C) water (Control) or solutions that added 10 mg g−1 soil tannic acid (TA), an imprecisely defined mixture of galloyl esters, gallic acid (GA), a phenol, or β-1,2,3,4,6-penta-O-galloyl-d-glucose (PGG), a hydrolyzable tannin. Soluble-C and N, in treatment supernatants, was measured to uncover evidence for sorption of treatments or effects on extraction of soil-N. Significant amounts of soluble-C, added with treatments, were not recovered in supernatants indicating sorption of nearly 90% of the PGG-C, about 75% of the TA-C but less than 25% of the GA-C in surface soil. Disappearance of soluble-C from treatment supernatants was accompanied by a corresponding reduction of total phenolic content. Treatments added a negligible amount of N to soil; but while PGG and TA reduced soluble-N, in extracts from surface soil, GA had little effect. Soluble-N in extracts was composed mainly of organic-N. Effects of tannins persisted in surface soil through 12 washings with hot water (80 °C), suggesting the formation of stable complexes with soil. The proportion of initial soil-C and N remaining after all extractions was higher in samples treated with PGG or TA than either the Control or GA treatment. We conclude PGG readily sorbs to soil and reduces the solubility of soil organic-N unlike GA, its simple monomeric constituent. These differences could be especially important near the surface where quantities of soil organic matter and biological activity are comparatively large and most easily affected by management. [Copyright &y& Elsevier] more...

Abstract: Tannins are plant-derived polyphenolic compounds that precipitate proteins, bind to metals and complex with other compounds. Solutions of tannic acid, or other phenolic compounds, were added to soil samples to determine if they would affect recovery of soluble soil carbon (WSC) or –nitrogen (WSN) or influence the extraction and composition of Bradford-reactive soil protein (BRSP), associated with glomalin. Tannic acid-C added with water was not completely recovered from samples and the amount of total net WSC and WSN recovered was reduced, suggesting formation of insoluble complexes. By comparison, non-tannin phenolics like gallic acid, or methyl gallate, had little effect on extraction of WSC or WSN while a simple gallotannin derived from tannic acid, 1,2,3,4,6-penta-O-galloyl-d-glucose (PGG), inhibited extraction most. The C and N concentrations in BRSP increased when soil samples were treated with tannic acid or PGG before extraction, a procedure that includes autoclaving. Increases were greatest in the 10–20cm compared to 0–5cm depth. Accompanying these were declines in the ratio of absorbance at 465 and 665nm (E4/E6 ratio) of BRSP extracts suggesting formation of larger or heavier molecules. In contrast, C and N composition in lyophilized BRSP was unaffected or even slightly reduced when tannic acid or PGG were added to the BRSP extract solution after the extraction process. We conclude that some tannins can reduce the solubility of labile soil C and N, at least temporarily and given unpredictability of response associated with phenolic substances, the Bradford assay should not be relied on to quantify pools or composition of soil proteins like glomalin. [Copyright &y& Elsevier] more...

• PGG and EA could strongly interact with BSA and showed pH-dependent binding. • PGG binding with BSA results an obvious conformational change. • PGG has obvious effects on the structure and function of BSA. • Phenolic acids addition might cause denaturation of protein. Fluorescence techniques and circular dichroism (CD) were utilized to investigate the interactions of a typical gallotannin 1,2,3,4,6-penta- O -galloyl- β -D-glucopyranose (PGG) and two simple phenolic compounds ellagic acid (EA) and gallic acid (GA) with bovine serum albumin (BSA). Fluorescence experiments showed that PGG and EA could strongly interact with BSA. The binding constants showed a pH-dependent binding of phenolic acids by BSA. The CD spectra revealed that GA, EA and PGG has slight effect on the secondary structure of BSA at the low concentration (50 μM). However, obvious alterations of the secondary structure of BSA were observed at high concentrations (from 100 μM to 500 μM). The interaction of GA, EA and PGG at high concentrations with BSA caused an unfolding of the secondary structure of BSA. PGG has a greater impact on the secondary structure of BSA when compared with small molecule compounds GA and EA. [ABSTRACT FROM AUTHOR] more...

• HFD consumption alteres the expression of genes involved in lipid metabolism. • PGG reduces HFD-mediated body weight gain and hepatic steatosis. • PGG reverses HDF-induced alterations in hepatic lipid metabolic gene expression. • PGG, a well tolerated natural product, holds the potential for NAFLD treatment. Non-alcoholic fatty liver disease (NAFLD) is currently the most frequently occurring liver disorder in the world. However, a specific drug for the treatment of patients with NAFLD is not available. Therefore, the discovery of novel compounds for the treatment of NAFLD and elucidation of the underlying mechanisms of therapeutic drugs that can be used to treat this disease are urgently needed. 1,2,3,4,6 penta- O -galloyl-β- d -glucose (PGG) is known to exert anti-inflammatory, antidiabetic, and hepatoprotective effects. However, little is known about the therapeutic potential of PGG in NAFLD. In this study, we investigated the effects of PGG on a high-fat diet (HFD)-induced mouse model of NAFLD. PGG was co-administered along with an HFD to C57BL/6 mice. After eight weeks of treatment, serum biochemistry, liver steatosis, and lipid metabolism-related genes were examined. The results showed that PGG treatment significantly reduced HFD-induced gain in body weight, liver steatosis, and leukocyte infiltration in a dose-dependent manner. Furthermore, PGG treatment markedly reduced serum triglyceride and glucose levels in HFD mice. Moreover, alterations in the mRNA expression of genes involved in lipid metabolism, including Hmgcr , Acc1 , Abca1 , Mttp , and Cd36 , observed in the livers of HFD-treated mice were significantly reversed by PGG treatment. PGG significantly reduced HFD-induced protein expression of CD36, which is associated with fatty acid uptake, insulin resistance, hyperinsulinemia, and increased hepatic steatosis, in the liver of HFD mice. These results suggest that PGG inhibits HFD-induced hepatic steatosis and reverses HFD-induced alterations of gene expression in lipid metabolism. PGG has been shown to be well tolerated; therefore, it has potential uses in NAFLD treatment. [ABSTRACT FROM AUTHOR] more...

The compound 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), a gallotannin present in various plants such as Rhus chinensis Mill and Paeonia suffruticosaic>, has a broad spectrum of antiviral effects. The present study investigated its potency against infection of mice with rabies virus (RABV). Results demonstrated that PGG strongly inhibited virus titers (50-fold), viral mRNA expression (up to 90%), and protein synthesis in vitro. Importantly, we found that PGG not only suppressed viral adsorption and entry, but also directly inactivated RABV through suppression of autophagy by mediating activation of the mTOR-dependent autophagy signaling pathway. In vivo, PGG (10 mg/kg) alleviated the clinical symptoms and reduced the mortality of infected mice by 27.3%. Collectively, our results indicate that PGG has potent anti-RABV effect, and merits further investigation as an anti-RABV drug. [ABSTRACT FROM AUTHOR] more...