Search

Cancer is one of the major reasons for mortality across the globe. Many side-effects are associated with the formulations available in the market, affecting the quality of life of the patients. This has caused the researchers to find an alternative source of medications, such as herbal medicine, showing a promising effect in anticancer treatment; one such source is Pomegranate, which belongs to the family Punicaceae. Punica granatum contains many polyphenols that have antioxidant, antidiabetic, and therapeutic effects in the treatment and management of metabolic and cardiovascular diseases, as well as a favourable effect on anticancer therapy. Polyphenols like punicalin, punicalagin, and ellagic acid are a few of the many compounds responsible for the anticancer activity of pomegranate. Many preparations of pomegranate, such as Pomegranate Juice (PJ), Pomegranate seed oil (PSO), Pomegranate peel extract (PoPx), etc. are used in various clinical studies. These polyphenols show anticancer activity by either arresting the cell cycle in the G2/M phase, inducing apoptosis or damaging the DNA of tumor cells. This review explicitly discusses the role and mechanism of bioactives obtained from the pomegranate in the treatment and management of cancer. The chemical structure, properties, and role of pomegranate in the treatment of breast, lung, thyroid, colon, and prostate cancer have been focused on in detail. This review also discusses various targeted drug delivery approaches for tumour treatment as well as patented preparation of pomegranate compounds along with the ongoing clinical trials.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (Mpro) inhibitors are considered as potential treatments for coronavirus disease 2019, and dietary polyphenols show promise in SARS-CoV-2 Mpro inhibition based on in silico studies. In the present study, we utilize a combination of biochemical-, surface plasmon resonance-, and docking-based assays to evaluate the inhibition and binding affinities of a series of tannins and their gut microbial metabolites on SARS-CoV-2 Mpro. The tested compounds (2–50 μM) were hydrolyzable tannins, including ellagitannins (punicalagin and ellagic acid) and gallotannins (tannic acid, pentagalloyl glucose, ginnalin A, and gallic acid), and their gut microbial metabolites, urolithins and pyrogallol, respectively. They inhibited SARS-CoV-2 Mpro (by 6.6–100.0% at 50 μM) and bound directly to the Mpro protein (with dissociation constants from 1.1 × 10–6 to 5.3 × 10–5 M). This study sheds light on the inhibitory effects of tannins and their metabolites on SARS-CoV-2 Mpro.

Aims: This study aims to explore the efficacy of punicalagin (PG) on diabetic cardiomyopathy (DCM), with a specific focus on the mechanisms underlying the effects of PG on mitochondrial fusion/fiss...

Background Pomegranate juice has gained attention for its health properties, becoming consequently a highly demanded product. The revival of the pomegranate in Italy, as in other Mediterranean countries, starts with the planting of new intensive orchards characterized by both the new cultivation technique and new varieties. As a result of growing demand and high productivity, pomegranate could become an interesting crop to diversify farm income. This study seeks to determine the aril juice quality attributes and bioactive compounds of six pomegranate cultivars ('Mollar', 'Dente di cavallo', 'Acco', 'Jolly red', 'Wonderful' and 'Wonderful Super') and two local ecotypes ('Eco BA' and 'Eco FG') grown in Apulia region, southern Italy. Results The aril juices were evaluated for their main physicochemical properties (yield, color, pH, total soluble solids content, titratable acidity, sugar-acid ratio), chemical and bioactive compounds (vitamin C, phenolics, anthocyanins and antioxidant activities). 'Eco BA', 'Mollar' and 'Jolly red' genotypes were characterized by the highest maturity index, and then could be considered to be sweet-sour in taste. Total phenols and antioxidant activity were higher in 'Dente di cavallo' and 'Eco FG' genotypes. 'Eco FG' was also the richest in vitamin C, punicalagin and ellagic acids, while 'Dente di cavallo', 'Acco' and 'Wonderful' showed the highest content of the detected anthocyanin compounds. Conclusion These results contribute to current knowledge about chemical composition, phenolic contents, anthocyanin profiles and antioxidant activity of pomegranate juice from different genotypes, showing in most cases an appreciable juice quality and bioactive profile, although significant differences among them were detected. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Objectives: We aimed to investigate the protective potential of Punica granatum L. fruit rind extract (PFE) containing punicalagin (10.3% W/W), ellagic acid (EA) (2.7%W/W) in vincristine (75 µg/kg ...

The antibacterial action of pomegranate peel against plant pathogen Ralstonia solanacearum has been focused in this study. We identified the chemical composition of pomegranate peel polyphenols (PPPs) and expanded their antibacterial spectrum by adding a new member R. solanacearum. PPPs were consisting of punicalagin, ellagic acid, catechin, gallic acid, epicatechin, and chlorogenic acid. Although the monomers exhibited strong antibacterial effect, PPPs performed better than individual ones. PPPs significantly hindered bacterial multiplication and swimming motility, and severely weakened the stability and integrity of the cell membrane. Bacterial biofilm formation was affected by PPPs in both time and concentration dependent manners. Punicalagin could bind the functional domains of bacterial transcriptional regulator PhcA when cell membrane integrity was impaired, resulting in the disordered regulation network and successive bacterial damage. We delineated the antibacterial mechanism of PPPs on both cell and molecular level with the aid of state of art analysis method and technology.

Punicalagin, a bioactive ellagitannin predominantly found in Pomegranate, has a wide range of health benefits including potent antioxidant properties. The metabolism of punicalagin in human body produces urolithins and ellagic acid. Ellagic acid is a natural phenolic antioxidant and is also known for its antiproliferative activities. Terminalia ferdinandiana (Kakadu plum) was reported to be a rich source of ellagic acid. In this study, an UHPLC-MS/MS method was developed and validated for accurate determination of ellagic acid levels and bioactive ellagitannins (punicalagin and castalagin). Total ellagic acid content in the fruits and leaves were 2.76 and 9.54 g/100 g DW. Punicalagin contents in the fruits and leaves were 74 and 49 mg/100 g DW, and castalagin contents were 1.1 and 0.8 mg/100 g DW. To the best of our knowledge, this is the first report about punicalagin and castalagin concentrations in Kakadu plum fruits and leaves. The findings are very promising regarding the potential use of Kakadu plum fruit and leaf extracts as natural preservatives in the food industry.

Background Insulin resistance, defined as a diminished ability to respond to the stimulation of insulin, is the main line for a variety of metabolic-related diseases. Punicalagin (PU), a hydrolyzable tannin of pomegranate juice, exhibits multiple biological properties, including anti-oxidant, anti-cancer and anti-inflammatory activities. Objective This research study aimed at determining the protective effect of PU on insulin resistance and to uncover the underlying mechanism based on the gut microbiota, IKKβ/NF-κB pathway, and autophagy. Design An insulin resistance animal model was established using C57BL/6 mice fed with a high-fat diet (HFD) for 8 weeks. The model included two groups continuing a HFD for 12 weeks with or without administering via gavage with PU 20 mg/kg/day. Changes in fasting plasma glucose levels, fasting serum insulin levels, glucose and insulin tolerance, glycolipid metabolism, gut microbiota composition (16S rRNA gene sequencing), inflammatory responses, and autophagy in the liver were evaluated. Body weight gain, glycolipid metabolic disorder, liver injury, as well as systemic and hepatic insulin sensitivity, were significantly attenuated after supplementing with PU. Results This research study revealed that PU alleviated HFD-induced glucose and lipid disorders, liver injury and insulin resistance; decreased the Firmicutes/Bacteroides ratio, decreased the abundance of Coprococcus and Anaerotruncus, and increased Rikenellaceae; and decreased serum and liver tumor necrosis factor-alpha and interleukin-1β levels, inhibited liver IKKβ and NF-κB phosphorylation; and increased liver autophagy-related proteins LC3-II, P62, and Beclin1, and increased the number of liver autophagosomes. Conclusion PU can improve HFD-induced insulin resistance, improved liver glucose and lipid metabolism disorder and liver injury, and the potential mechanism is that PU inhibited the IKKβ/NF-κB inflammatory pathway by regulating gut microbiota homeostasis and up-regulating liver autophagy activity.

Mingcheng Huang,1,* Keping Wu,1,* Shan Zeng,2,* Wenfen Liu,1 Tianjiao Cui,1 Zhiqing Chen,1 Lian Lin,1 Dongying Chen,3 Hui Ouyang1 1Department of Nephrology, Kidney and Urology Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, ShenZhen, Guandong, People’s Republic of China; 2Department of Rheumatology, The First Affiliated Hospital of Jinan University, Guangzhou, Guandong, People’s Republic of China; 3Department of Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongying Chen; Hui Ouyang Email chendy3@mail.sysu.edu.cn; ouyh23@mail.sysu.edu.cnBackground: The aggressive phenotype of fibroblast-like synoviocytes (FLSs) is essential in the synovitis and bone destruction in rheumatoid arthritis (RA). Punicalagin is a natural polyphenol extracted in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumor properties suggesting it may be a potent drug for RA therapy. However, there is paucity of information on its effect in RA.Objective: To investigate the effects of punicalagin on synovial inflammation and bone destruction in RA.Methods: FLSs were isolated from synovial tissue of RA patients. The mRNA levels were evaluated by quantitative real-time PCR. Western blot was used for protein level measurements. The secretion of pro-inflammatory cytokines and metalloproteinases (MMPs) was detected by ELISA assays. Edu staining assays were carried out to investigate the proliferation of FLSs. Cell migration was assessed by Boyden chambers, wound scratch assays and F-actin staining in vitro. The intracellular translocation of nuclear factor kappa B (NF-κB) was investigated using immunofluorescence. The effects of punicalagin in vivo were measured by using collagen-induced arthritis (CIA) mice.Results: Punicalagin treatments significantly reduced the TNF-α induced expressions of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-17A) and MMPs (MMP-1 and MMP-13) of RA FLSs. Punicalagin also suppressed the proliferation and migration of RA FLSs. Moreover, punicalagin (50mg/kg/d) alleviated arthritis severity and bone destruction, and decreased serum IL-6 and TNF-α in CIA mice. Further mechanism studies indicated that punicalagin blocked NF-κB activation via suppressing phosphorylation of IKK and IkBα, and preventing the translocation of 65.Conclusion: Our findings suggested that punicalagin might be one of natural therapeutic compounds for relieving RA progress via suppressing FLSs inflammation and migration through modulating NF-κB pathways.Keywords: rheumatoid arthritis, punicalagin, fibroblast-like synoviocytes, migration, pro-inflammatory cytokines

Background Ultraviolet (UV) rays are the major environmental factor that damage skin physiology causing deleterious effects such as oxidation, photoaging and pigmentation. There has been considerable interest in using botanicals to prevent skin damages caused by UV irradiation. Aim In this study, three plant extracts were tested either individually or combined together (mixture) as well as their corresponding main active compound: pomegranate/punicalagin, osmanthus/verbascoside and olive/hydroxytyrosol. We evaluated the whitening and anti-photoaging properties of the nutritional mixture using 2D human culture model and a 3D full-thickness pigmented skin model exposed to UVB and UVA. Methods For exploring skin pigmentation, oxidation and aging, we performed cell viability, tyrosinase activity and melanin content assays as well as histology analysis (Whartin–Starry staining), immunodetection (PMEL, MDA, collagen type I and elastin) and carbonylated proteins analysis by electrophoresis separation. Results Results showed that the pomegranate extract and the active molecule punicalagin could reduce the tyrosinase activity and melanin content in melanocytes (P < 0.05). The mixture, pomegranate extract and punicalagin inhibited the melanin production and pre-melanosomal protein (PMEL) expression in the 3D skin pigmented model (P < 0.001). Furthermore, the mixture treatment repaired the expressions of collagen I and elastin decrease by UV exposure (P < 0.01). The mixture also significantly decreased lipid peroxidation (P < 0.001) and carbonylated proteins (P < 0.05) in the skin model compared to the UV-exposed condition. Conclusion To conclude, the mixture composed of pomegranate, osmanthus and olive extracts protects human skin from UV rays deleterious effects and exhibits antioxidative, anti-aging and skin whitening properties. Our data suggested pomegranate contributed to the whitening properties of the mixture notably through its main active compound, punicalagin. The mixture might be a good candidates for further development as natural antioxidant and skin care product.

In recent years, consumption of pomegranate products have increased with the understanding of its benefits to human health, and pomegranate peel has become one of the most common wastes in the food industry. In this study, some physicochemical, antioxidant, in vitro bioaccessibility and antidiabetic properties of peels of Hicaz, Devedisi, and Zivzik pomegranate varieties were determined. The average values of total phenolic contents, total flavonoid contents, Punicalagin A, Punicalagin B, Ellagic acid, DPPH and ABTS of pomegranate peels were 26916.66 mg GA eq./100 g dw, 17316.37 mg QE/100 g dw, 15847.74 mg/100 g dw, 14693.31 mg/100 g dw, 783.82 mg/100 g dw, 188.59 mmol Trol. eq./g dw, and 99.01 mmol Trol. eq./g dw respectively. Their average values in vitro bioaccessibilities were 43.13, 27.82, 62.61, 73.79, 16.96, 57.22 and 31.71%, respectively. It was determined that the initial total phenolic content, total flavonoid content, ellagic acid and antioxidant activity levels of the samples significantly decreased after digestion. Nevertheless, bioaccessibility of Punicalagin A and Punicalagin B significantly protected after digestion. alpha-amylase and alpha-glucosidase inhibitory activities of pomegranate peels range from 0.06 to 0.14 mg/L and 3.01 to 3.64 mg/L respectively. It was determined that all three varieties showed higher antidiabetic activity compared to acarbose. As a result, pomegranate peel ellagitannins after in vitro digestion had high bioaccessibility. Pomegranate peel with high antioxidant and antidiabetic activities is a natural source that can be used in the pharmacology, food and cosmetics industry.

Pomegranate cv. ‘Wonderful’ fruit are susceptible to chilling injuries of the peel (CIp) when stored at 7 °C in modified-atmosphere bags for more than 3 months. The damage, manifested as superficial browning, is restricted to the fruit skin, i.e., the outer colored layer of the peel. To characterize possible causes of CIp development, fruit were collected at early harvest—when the premature fruit are poorly colored and susceptible to CIp development, and at late harvest—when mature fruit have fully red skin and less susceptibility to CIp. Skin samples were collected on day of harvest and at different time points during storage. Anatomical study of skin with CIp disorder showed a broken cuticle layer with underlying degenerated cells. A high total phenol content, which is associated with high antioxidant capacity, was not sufficient to prevent the development of CIp in the premature fruit. The concentration of punicalagin was the same for premature and mature skin at harvest and during storage, and therefore not associated with CIp development in the premature fruit skin. Furthermore, the expression of antioxidant-related genes CAT2, SOD and GR2 was similar for both premature and mature fruit skin. Poor pigmentation of the premature fruit skin and chilling-induced downregulation of key anthocyanin-biosynthesis genes were associated with CIp development. High total phenol concentration combined with high expression of the gene encoding PPO was also associated with CIp; however, high expression ratio of PAL to PPO was found in mature skin, and may be associated with reduced CIp disorder. The results presented suggest future possibilities for controlling the CIp phenomenon.

Pomegranate (Punica granatum) acts as a therapeutic fruit possessing different bioactive compounds. Different compartments of pomegranate (P. granatum) like seed, peel, juice and leaves are rich in potential bioactive compounds. Pomegranate contains sinapyl, coniferyl, ellagic acid, cinnamic acid, genistein, linoleic acid, anthocyanin, gallic acid, catechin, quercetin, rutin, kaempferol, cyanidin, punicalin, delphinidin, punicalagin, chlorogenic acid, coumaric acid, luteolin and pelletierine alkaloids, flavonoids, anthocyanin and caffeic acid. Pomegranate also exhibits significant anti-oxidative, anti-hypertensive, cardioprotective and anti-diabetic properties and anti-carcinogenic possessions including prevention of prostate cancer; reduction in colon inflammation, prevention of skin tumorigenesis, improvement in renal function and reduction in metastatic melanoma growth. This review summarizes the current available data on the phytochemistry, bioavailability and therapeutic importance of potential bioactive compounds of pomegranate.

Pomegranate peel is a rich source of various phenolics. Many extraction methods were developed and utilized for pomegranate peel extraction (PPE) with varying effect on its bioactive compounds. We hypothesized that micro wet milling (MWM) can be used to extract such compounds from fresh peel without drying to powder, as their particle size is reduced to micrometers. This will preserve the bioactive compounds as no heat treatment is involved in this proposed extraction method. To assess the MWM extraction process, response surface methodology (RSM) was used to determine the optimum extraction conditions. The main influential factors such as rotational speed (RS) 20–50 rpm, solid to solvent ratio (SS) 5–30 g/100 mL, and ethanol to water ratio (EW) 30–80% were optimized for total phenolic content (TPC), total anthocyanin content (TAC), punicalagin, ellagic acid (EA), gallic acid (GA), catechin, and epicatechin. The optimum operational conditions were 50 rpm of RS, 19.62 g/100 mL of SS, and 49.65 % v/v of EW. The most significant influential factor for pomegranate peel extraction was SS. The optimum phenolic compound values were 225.7 mg GAE/g dw of TPC, 3.1 mg/g dw of TAC, 71.6 mg/g dw of punicalagin, 6.9 mg/g dw of ellagic acid, 6.2 mg/g dw of gallic acid, 13.1 mg/g dw of catechin and 14.8 mg/g dw of epicatechin. Validation of the model and its comparison with the results obtained from the ultrasonic bath extraction method and scanning electron microscopy (SEM) revealed that MWM can be used to mill the peel into micro-scale particles making the extraction of pomegranate peel phenolics easier.

Sleep deprivation has deteriorating effects on cognitive functions and activation of brain inflammation mechanisms has been reported by some studies following total sleep deprivation. Some studies have reported the health benefits of punicalagin, a main abstract from Punica granatum L., including those for the treatment of Alzheimer’s disease. The antioxidant characteristic of punicalagin and the fact that sleep deprivation accelerates mediators of inflammation led us to further explore the possible neuroprotective role of punicalagin in total sleep deprivation memory impairment in a rat model. In this study, male Wistar rats were implanted with a canula in the lateral ventricle to receive intracerebroventricular injections (drug or vehicle). The animals were trained for the passive avoidance test and then received intracerebroventricular injections of different doses of punicalagin (0.001, 0.01, or 0.1 μg/rat). Then, they were placed in the sleep deprivation apparatus for 24 hours and tested afterwards for memory retrieval and locomotion. Our results indicated that 24 hours of total sleep deprivation impaired memory processes. PG microinjection before TSD did not prevent the deteriorating effect of total sleep deprivation on memory, and only showed a tendency of restoring the memory impairment. Comparison of the locomotor activity between the animals in different groups showed a significant increase in the total sleep deprivation sham groups that received two of the highest doses of punicalagin. Considering the reported beneficial actions of PG by other studies, further investigation is needed into the possible effects of PG in memory alterations.

The present study investigated to know whether the pomegranate polyphenol punicalagin (PU) can ameliorate oxidative stress and pathological alterations induced by a calorie rich diet comprised of fat and fructose. Male Swiss albino mice were fed normal pellet (Control) or high fat-high fructose diet (HFFD) for 60 days. PU (30 or 60 mg/kg bw) was administered orally for the last 15 days for both dietary groups. Measurement of TBARS, AOPP and FRAP in plasma, histopathology of liver and brain, assessment of oxidative damage in brain tissues, and blood brain barrier function were carried out. HFFD mice showed an increase in the levels of TBARS and AOPP, and a decline in FRAP. PU administration to HFFD mice reduced the levels of TBARS and AOPP and improved FRAP significantly. Histopathology results showed fatty changes and inflammatory infiltration in the liver of HFFD mice. Cortex and hippocampus of HFFD mice confirmed the presence of degenerating neurons with shrunken cytoplasm and pyknotic nuclei. PU treatment caused significant hepato and neuroprotective effects, and among the two doses the high dose of PU (60 mg/kg) showed more pronounced effects than the low dose (30 mg/kg). The immunohistochemical localization of the markers of oxidative damage to proteins (3-NT), lipids (4-HNE) and DNA (8-OHG) was increased in brain tissues of HFFD mice and upon PU administration (60 mg/kg) the levels of these oxidative stress markers were significantly decreased. Our findings clearly suggest that PU can modulate oxidative stress and could be a potential candidate for treating neurodegenerative processes associated with calorie excess.

Punicalagin is the most popular ellagitannin found in pomegranate husk and is well known to reduce the risk of cancer and cardiovascular diseases (CVDs). The present work describes a novel method for the preparation of nanoparticles of Punicalagin using pomegranate (Punica granatum) since the use of Punicalagin in bulk form is associated with many problems. In this study, nanoparticles of Punicalagin were synthesized, characterized using various techniques, and further evaluated for their antioxidant, antibacterial, and antiproliferative potential using HepG2 cancer cells. DLS analysis revealed that the average size of nanoparticles of Punicalagin was 87 nm, whereas SEM analysis confirmed spherical shaped nanoparticles with size ranging from 90 to 116 nm. HPLC studies confirmed the presence of Punicalagin in synthesized nanoparticles. The results also revealed that nanoparticles of Punicalagin were nearly four times more potent antioxidants than bulk and possessed an inhibition zone of about 13 mm. The response of antiproliferative assay showed that the nanoparticles of Punicalagin caused nearly 44% reduction while bulk form showed only a 15% reduction in cell viability of cancerous cells at 100 µg/mL. The study suggests a great potential for use of the herbal drug in nano form to treat cancer as compared to its bulk counterparts.

Antimicrobial resistance poses a serious threat to human health worldwide. Plant compounds may help to overcome antibiotic resistance due to their potential resistance modifying capacity. Several botanical extracts and pure polyphenolic compounds were screened against a panel of eleven bacterial isolates with clinical relevance. The two best performing agents, Cistus salviifolius (CS) and Punica granatum (GP) extracts, were tested against 100 Staphylococcus aureus clinical isolates, which resulted in average MIC50 values ranging between 50–80 µg/mL. CS extract, containing hydrolyzable tannins and flavonoids such as myricetin and quercetin derivatives, demonstrated higher activity against methicillin-resistant S. aureus isolates. GP extract, which contained mostly hydrolyzable tannins, such as punicalin and punicalagin, was more effective against methicillin-sensitive S. aureus isolates. Generalized linear model regression and multiple correspondence statistical analysis revealed a correlation between a higher susceptibility to CS extract with bacterial resistance to beta-lactam antibiotics and quinolones. On the contrary, susceptibility to GP extract was related with bacteria sensitive to quinolones and oxacillin. Bacterial susceptibility to GP and CS extracts was linked to a resistance profile based on cell wall disruption mechanism. In conclusion, a differential antibacterial activity against S. aureus isolates was observed depending on antibiotic resistance profile of isolates and extract polyphenolic composition, which may lead to development of combinatorial therapies including antibiotics and botanical extracts.

DownoadedFomP125171694ondaed27Oc2021 According to the World Health Organization, the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or COVID 19 has caused a pandemic around the world. The rapid infection has posed significant threats to international health and the economy. Till now, there is no treatment available. This contribution focuses on specific phytochemicals, essential oils and probiotics against SARS-CoV-2. Different electronic scientific databases and search engines were employed. The potential effects of phenolics, flavonoids, tannins, alkaloids, saponins and essential oils from different edible sources as well as probiotics against SARS-CoV-2 and coronaviruses have been reviewed. Inhibition mechanisms on SARS-CoV-2 and other coronaviruses either experimented or predicted by molecular docking modeling software were presented. The confirmed compounds belong to the alkaloids, tannins and terpenoides bioactive classes as pedunculagin, tercatain, punicalin, punicalagin, punicalin, geraniin, chebulagic acid, punicalagin, emetine and ginkgolide A can be preventing the infection or introducing treatments against SARS-CoV-2 and other coronaviruses. Lactobacillus plantarum strain N4, Enterococcus faecium NCIMB 10415, Lactobacillus salivarius prevented the infection by trapping the coronavirus or stimulated the cellular defense by the production of nitric oxide. Utilize the rich plants with bioactive compounds or use them in the preparation of functional foods is a simple way to provide people with protection against SARS-COV-2.

Alcohol consumption is a tradition in most cultures but are increasingly being arised as possessing a potential for misuse. Punicalagin is a phenolic compound that is found in forms alpha and beta in pomegranates. In this study, the protective role of punicalagin on oxidative stress, inflammation and DNA damage caused by ethanol (EtOH) in liver tissue were examined. Wistar albino rats were divided into 4 groups as control, eth, punicalagin, EtOH EtOH + punicalagin. In EtOH groups, rats were treated with EtOH (4g/kg) for 21 days, in punicalagin groups, rats were treated with punicalagin (4 mg/ kg) for 21 days. In the liver tissue, superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) and glutathione (GSH) levels, in serum AST, ALT, LDH activities and TNF-alpha, IL-6 levels were measured. Genotoxicity was evaluated using comet assay. Based on these experimental results, while EtOH increased ALT, AST and LDH enzyme activies and induced inflammation and oxidative stress. Punicalagin reduced IL6, TNF-alpha, MDA levels, ALT, AST, LDH enzyme activities and increased SOD, CAT activities and GSH levels. EtOH significantly increased the percentage of damaged cells (type II, III and IV) and genetic damage index compared to the other groups (control, punicalagin and EtOH +punicalagin). Punicalagin was not genotoxic compared to the control. Furthermore, punicalagin reduced the genotoxic effect, induced by EtOH, with the sharp decrease in damaged cells (from 14.00 +/- 1.22 to 2.20 +/- 1.30) and genetic damage index (from 1.20 +/- 0.05 to 0.14 +/- 0.05). Punicalagin has antioxidant, anti-inflammatory and protective role against to ethanol induced liver toxicity.

Salmonella, a bacterial foodborne pathogen, can contaminate meat, milk, and vegetables. While appropriate measures are available to control Salmonella, the inhibitory phytochemicals from plants are gaining increased attention. Punicalagin, a natural antimicrobial, is one of the main active tannins isolated from Punica granatum L. To obtain a broader understanding of the effect of punicalagin on the cell membranes of Salmonella Typhimurium, the growth curves, extracellular potassium concentration, release of cell constituents, intracellular pH, membrane potential, and morphological features were characterized to elucidate the mechanisms of action. Treatment with punicalagin induced an increase in the extracellular concentrations of potassium and a release of cell constituents. A higher pH gradient, an increase in the intracellular pH, and cell membrane depolarization were observed after punicalagin treatment. Electron microscopy observations showed that the cell membrane structures of Salmonella Typhimurium were damaged by punicalagin. It is concluded that punicalagin inhibits the proliferation of Salmonella Typhimurium and destroys the integrity of the cell membrane, leading to a loss of cell homeostasis. These findings indicate that punicalagin has the potential to be developed as a future alternative to control Salmonella Typhimurium contamination in foods and reduce the risk of salmonellosis.

Influenza A virus (IAV) causes great morbidity and mortality worldwide every year. However, there are only a limited number of drugs clinically available against IAV infection. Further, emergence of drug-resistant strains can render those drugs ineffective. Thus there is an unmet medical need to develop new anti-influenza agents. In this study, we show that punicalagin from plants possesses strong anti-influenza activity with a low micromolar IC50 value in tissue culture. Using a battery of bioassays such as single-cycle replication assay, neuraminidase (NA) inhibition assay, and virus yield reduction assay, we demonstrate that the primary mechanism of action (MOA) of punicalagin is the NA-mediated viral release. Moreover, punicalagin can inhibit replication of different strains of influenza A and B viruses, including oseltamivir-resistant virus (NA/H274Y), indicating that punicalagin is a broad spectrum antiviral against both IAV and IBV. Further, although punicalagin targets NA like oseltamivir, it has a different MOA. These results suggest that punicalagin is an influenza NA inhibitor that may be further developed as a novel antiviral against influenza viruses.

Lipid metabolism balance plays a vital role in maintaining normal levels of sterols, triglycerides, and free fatty acids (FFA). Inhibiting FFA-induced lipotoxicity is considered a highly potential treatment for non-alcoholic fatty liver disease (NAFLD) and other lipid metabolism diseases. Punicalagin (PU), a pomegranate-derived polyphenol, has been found to effectively regulate lipid metabolism and prevent fatty liver, cardiovascular and other chronic diseases caused by lipid metabolism disorders. In the present study, we found that PU protects HepG2 cells from palmitic acid (PA)-induced lipapoptosis. Silent information regulator 1 (SIRT1) plays a key role in protecting against lipapoptosis in HepG2 cells. Knockdown of SIRT1 significantly diminished the protective effect of PU. Besides, PU could be able to reactivate weakened autophagy and inhibit PA-induced ER stress. Our findings supported that PU can effectively attenuate FFA-induced lipotoxicity via activating SIRT1/autophagy and inhibiting ER stress.

Punicalagin is a phenolic compound extracted from Lafoensia pacari A. St.-Hil (Lythraceae) leaves. It has demonstrated interesting activity against pathogenic fungi, e.g., Cryptococcus gattii and Candida albicans, by inhibiting fungi growth in a minimum inhibitory concentration (MIC) at 4 μg/mL. However, the mechanisms behind its antifungal action are not well understood. In this study, certain parameters were investigated, by transmission electron microscopy, ergosterol synthesis inhibition, and flow cytometry analyses, to gain insight into the possible biological targets of punicalagin (4 or 16 μg/mL) against yeast cells. Data showed that, in contrast to untreated cells, punicalagin triggered severe ultrastructural changes in C. gattii and C. albicans, such as disorganization of cytoplasmic content and/or thickened cell walls. In addition, it caused a decrease in yeast plasma membrane ergosterol content in a concentration-dependent manner. However, it was unable to bring about significant fungal cell membrane rupture. On the other hand, punicalagin (16 μg/mL) significantly arrested C. albicans and C. gattii cells at the G0/G1 phase, with a consequent reduction in cells at the G2/M phase in both fungi isolates, and thereby prevented progression of the normal yeast cell cycle. However, these alterations showed no involvement of reactive oxygen species overproduction in C. albicans and C. gattii cells, although punicalagin triggered a significant loss of mitochondrial membrane potential in C. albicans. These findings suggest that punicalagin is a promising plant-derived compound for use in developing new antifungal therapies.

Osteosarcoma is the most common primary malignant bone tumor among children and young people and is associated with poor prognosis. Punicalagin is an antioxidant ellagitannin found in pomegranate juice with known antiproliferation and anti-angiogenesis properties. However, the antitumor effect of punicalagin on osteosarcoma requires further investigation. In the present study, the inhibitory effect of punicalagin on proliferation and invasion was evaluated in one human osteoblast cell line (hFOB1.19) and three human osteosarcoma cell lines (U2OS, MG63 and SaOS2). The cancer cell apoptosis ratio was determined using flow cytometry. NF-κB signaling in these cells was also evaluated using western blotting analysis. A subcutaneous tumor xenograft model was initiated to study the efficacy of punicalagin on osteosarcoma development and angiogenesis in vivo. Punicalagin treatment significantly decreased osteosarcoma cell proliferation and increased apoptosis. In addition, the invasion potential of these cells in a transwell assay was also dramatically suppressed in osteosarcoma cells. Punicalagin not only induced the degradation of IκBα but also the nuclear translocation of p65, suggesting the attenuation of NF-κB signaling pathway following treatment. Moreover, punicalagin markedly downregulated interleukin (IL)-6 and IL-8 levels, which was consistent with the inhibition of NF-κB signaling. An NF-κB activator could reverse these effects. Using a tumor xenograft mouse model, it was demonstrated that punicalagin exposure inhibited osteosarcoma growth and angiogenesis in vivo. These observations confirmed the suppressive effect of punicalagin against osteosarcoma malignancies. The underlying molecular mechanisms may include inhibition of the NF-κB signaling pathway.

Acrylamide (ACR) is widely used in industries. Oxidative stress and apoptosis pathways are important mechanisms behind ACR-induced hepatotoxicity and neurotoxicity. Regarding to antioxidant and antiapoptotic properties of punicalagin (PUN), the protective effect of this agent on ACR-induced toxicity in rat was evaluated. Rats were divided into seven groups: control, ACR (50 mg/kg/day, i.p.), PUN (10, 20, and 40 mg/kg/day, i.p.) plus ACR, vitamin E (200 mg/kg, i.p.) plus ACR, and PUN groups. After 11 days, the gait score test was evaluated. Then, the animals were sacrificed and the malondialdehyde (MDA) and glutathione (GSH) contents were determined in the brain and liver tissues. Apoptosis-involved factors and myelin basic protein (MBP) were determined by western blotting. Severe movement disorder, MDA enhancement, and GSH reduction in the brain and liver tissues were observed in ACR-treated animals. The Bax/Bcl2 ratio and caspase-3 levels were enhanced in the tested tissues. ACR elevated the level of aspartate aminotransferases and decreased serum protein and albumin concentration. PUN recovered movement disorders, changed the level of markers which are important in oxidative stress and reduced apoptosis. Also, PUN increased the MBP level which was reduced due to ACR toxicity. PUN can protect against ACR-induced toxicity through antioxidant and antiapoptotic properties.

Lafoensia pacari A. St.-Hil., Lythraceae, is used in Brazilian folk medicine to treat ulcer and gastritis; thus, it is important to conduct research so as to better understand its medicinal properties. The aim of this study was to assess the antisecretory and antiulcerogenic activities of lyophilized aqueous fraction and punicalagin isolated from leaves of L. pacari. Antisecretory gastric acid activity and antiulcerogenic activity were investigated by pyloric ligation-induced and indomethacin-induced gastric lesion models, respectively. Results show that the lyophilized aqueous fraction of L. pacari and punicalagin reduced the volume of gastric secretion, free acidity, and total acidity in mice 4 h after pyloric ligation, as well as the rate of gastric damage following the indomethacin administration model. Reduction percentages varied according to the dose of each treatment and showed statistical difference. This finding indicates that the lyophilized aqueous fraction of L. pacari and punicalagin exert an antiulcerogenic effect due to their acid antisecretory activity.

Increasing attention of plant derived therapeutic agents against cancer, investigating the anti-proliferative efficiency of plant derived chemicals have achieved increasing momentum for the design of anticancer drug. Punicalagin, dietary phytochemical altered the various cell signal transduction pathways associated with cell apoptosis and proliferation. This investigation was intended to examine the efficiency of punicalagin lying on cell viability so as to examine the molecular based punicalagin mechanism stimulated apoptosis via exploring the expression of Bcl-2 family proteins, and caspases also the cell cycle regulatory proteins p53 and NF-κB signaling in human cervical cancer cells. We also analyzed the morphological characteristic changes through mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, TUNEL assay, AO/EtBr analysis in cervical cancer cells. Our findings demonstrated that punicalagin repressed the viability of cervical cancer cells in a dosereliant mode via stimulating mitochondrial mediated apoptosis. Moreover, our this study demonstrated that punicalagin blocked cervical cancer cell proliferation and stimulated cell apoptosis by suppressing NF-kappa B activity. Hence our study suggested that punicalagin exhibits opposing actions on NF-kappa B signaling networks to block cancer cell progression acts as a classical candidate for anticancer drug designing. Keywords: Punicalagin, Cervical cancer, Apoptosis, ME-180 cells, NF-ƙB pathway

Pomegranate juices (PJs) were clarified using hydrocolloids [albumin (A), casein (C), chitosan (CH) and xanthan gum (XG)] and in combination with each other. The lowest turbidity was observed in PJs clarified with ‘CH+XG’ and ‘A+C+CH’. Unlike ‘CH+XG’, effects of albumin and its combinations on clarity were mainly related with the contents of ellagic acid (r = −0.861), α‐punicalagin (r = −0.761), rutin (r = −0.734), β‐punicalagin (r = −0.730) and total punicalagin (r = −0.713). ‘CH+XG’ caused the highest phenolic (602 mg L⁻¹) and anthocyanin (449 mg L⁻¹) contents, and the second highest Aₘₐₓ (0.811 ABS), resulting from copigmentation of delphinidin‐3‐glucoside and delphinidin‐3,5‐diglucoside with CH. Since A showed moderate copigmentation effect, A had lower hyperchromic effect than CH. Moreover, C reduced Aₘₐₓ, anthocyanin content and colour density when combined with other hydrocolloids. As a result, ‘CH+XG’ would be the best combination to obtain high clarity, maintain phenolics and anthocyanins and provide high copigmentation effect in PJ.

The aim of this work was to perform in silico analysis of selected biomolecules from Terminalia arjuna (T. arjuna) by using virtual screening, molecular docking and pharmacophore modeling. Reported 30 biomolecules of T. arjuna were used as ligands. Grip-based docking was carried out to produce the target-specific complex model using vLife MDS 4.4 software. Docked conformations of the selected T. arjuna biomolecules resulted in eight potential biomolecules namely Casuarinin, Luteolin, Pelargonidin, Arjunin, Castalagin, Punicalagin, Kaempferol and Quercetin with major interactions and exhibited good affinity to the residues of protein targets. Developed pharmacophore models have suggested minimum pharmacophoric features required in the biomolecule so as to show standard like activity. Interestingly, Casuarinin showed multiple inhibitions on phosphodiesterase 5A and sodium-potassium pump whereas Pelargonidin on phosphodiesterase 5A and beta-adrenergic protein targets. Conclusively, this study provides a suitable platform for discovery of novel inhibitors from natural source for heart disorders.

In this study, active and intelligent packaging films were developed by incorporating polypheol-rich pomegranate flesh extract (PFE) or pomegranate peel extract (PPE) into κ-carrageenan matrix. The structural, physical, pH-sensitive, antioxidant and antimicrobial properties of κ-carrageenan-PFE and κ-carrageenan-PPE films were compared for the first time. Results showed PFE was composed of cyanidin-3-O-glucoside (49.76%), peonidin-3-O-(6-malon)-glucoside (9.61%), malvidin-3-O-(6-acetyl)-glucoside (14.89%), pelargonidin-3-O- (6″-ethylmalonyl)-glucoside (7.05%), pelargonidin-3-O-(6-acetyl)-glucoside (9.51%) and isorhamnetin (9.18%). PPE was mainly composed of gallic acid (15.73%), malvidin-3-O-(6-acetyl)-glucoside (4.07%), epicatechin gallate (3.66%), luteolin (5.69%), vanillic acid (7.82%), caffeic acid (4.37%), punicalagin (39.96%) and ellagic acid (18.70%). The tensile strength, water vapor and UV light barrier ability of κ-carrageenan film were significantly promoted by the incorporation of PFE or PPE. Due to different polyphenolic compositions, κ-carrageenan-PPE films possessed higher UV light barrier, antioxidant and antimicrobial properties than κ-carrageenan-PFE films at the same extract incorporation levels. Nonetheless, κ-carrageenan-PFE films exhibited pH-sensitive property because of abundant anthocyanins in PFE. Notably, the physical and functional properties of κ-carrageenan-PFE and κ-carrageenan-PPE films were closely related to the content of extract. Our results suggested κ-carrageenan-PFE films could be further used as active and intelligent packaging, whereas κ-carrageenan-PPE films could be explored as active packaging in food industry.

Breast cancer (BC) is one of the most common malignancies worldwide. Punicalagin (PN), which is a type of polyphenol, has been reported to act as a tumor suppressor. This study aimed to investigate the effects of PN on cellular process in BC and its molecular mechanism. The effects of various doses of PN on cell viability, migration, and invasion capacities of MCF-7 and MDA-MB-231 cells were detected by CCK-8, wound-healing, and Transwell assays. Golgi phosphoprotein 3 (GOLPH3) was then transfected into the cells with or without PN treatment, and GPLPH3 expression level was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, and expressions of epithelial-mesenchymal transition (EMT)-related protein matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), E-Cadherin, and N-Cadherin were measured by Western blot. High dose of PN treatment (50 μM or higher) significantly inhibited viability, migration, and invasion of MCF-7 and MDA-MB-231 cells, while overexpressed GOLPH3 promoted cell viability, migration, and invasion, and partially reversed the effects of PN treatment on the BC cells. PN inhibited the expressions of GOLPH3, MMP-2, MMP-9, and N-Cadherin, and promoted E-Cadherin expression, while overexpression of GOLPH3 partly reversed above effects attributing to PN. Thus, PN suppresses cell viability and metastasis

In this study, eight different pomegranate (Punica granatum L.) cultivars from Turkey were evaluated for their antioxidant and cytotoxic effects on the MCF-7 breast cancer cell lines and MCF-10A breast fibrocystic epithelial cell lines with a focus on their chemical compositions by LC-MS/MS. Cell lines were treated with pomegranate juice extracts in different doses at selected time intervals (24th, 48th, and 72nd hour). Afterwards, WST-1 cell proliferation assay was performed to investigate the cytotoxicity of the extracts. Accordingly, all extracts decreased the cell viability of MCF-7 breast cancer cell lines and had no cytotoxic effect on the cell viability of MCF-10A cell lines. Among eight extracts, P7 (Izmir 1513), which was rich in anthocyanins such as cyanidin chloride (69.76 +/- 8.02 mu g/g extract), cyanidin-3-O-glucoside (903.66 +/- 101.89 mu g/g extract), and punicalagin (992.09 +/- 174.53 mu g/g extract), was found to demonstrate the strongest cytotoxic activity on MCF-7 breast cancer cell lines by decreasing the cell viability in half at 24th hour with an IC50 value of 49.08 mu g/ml. Practical applications Eight commercially valuable pomegranate (Punica granatum) cultivars from Turkey were examined. Pelargonidin, cyanidin, cyanidin-3-O-gl, callistephin, and delphinidin-3-O-gl were quantified. Two cultivars (P1 and P3) showed comparatively higher antioxidant effects. A cultivar (P7) showed strongest cytotoxic activity against MCF-7 breast cancer cell line. The cultivars have potential to be used as natural antioxidant and anticancer agents.

The pandemic caused by the new coronavirus has resulted in a global health emergency and has prompted an urgent need for new treatment strategies. No target-specific drugs are currently available for SARS-CoV-2, but new drug candidates targeting the viral replication cycle are being explored. A prime target of drug-discovery efforts is the SARS-CoV-2 main protease (Mpro). In this work, we identified a potential inhibitor for SARS-CoV-2 main protease using in silico methodologies. Molecular docking and molecular dynamics studies were carried out to ascertain the inhibitory action of α and β anomers of Punicalagin from fruit peel of Punica granatum against the Mpro protease. The molecular dynamics results revealed that the β-anomeric configuration of punicalagin allowed access to more hydrogen bonds and hydrophobic interaction leading to higher selectivity and specificity of β-anomer than α-anomer. Therefore, the β-anomer of Punicalagin could act as potential inhibitor against the main protease of SARS-CoV-2 and may act as a potential drug candidate.

PURPOSE This study aimed to investigate the anti-inflammatory effect and antifungal effect of punicalagin in murine fungal keratitis. METHODS We used in vitro and in vivo protocols to assess the anti-inflammatory effect and antifungal effect of punicalagin. In vitro, time kill and mycelial stain were done. In vivo, murine fungal keratitis was established and treated with PBS or PUN. clinical scores were taken on days 1, 3, and 5 post infection. The mRNA and protein levels of inflammatory factors were detected by RT-PCR and Western blot, and the number and location of macrophages were analyzed by flow cytometry and immunofluorescence. Also, fungal plate counting was used to assess the antifungal effect. DCFH-DA fluorescence Probe detected the ROS level. RESULTS In vitro, PUN showed activity against A.fumigatus. (A.F.), with MIC90 values of 250 μg/ml, and significantly reduced A.F. biofilm formation (p

Punicalagin, a major ellagitannin isolated from pomegranate, is proved to have various pharmacological activities with an undefined therapy mechanism. The objective of this research was to demonstrate the effect of punicalagin on anti-inflammatory and angiogenic activation in human umbilical vein endothelial cells (HUVECs) and their potential mechanisms. Endothelial-leukocyte adhesion assay was applied to evaluate primary cultures of HUVECs activation following tumor necrosis factor alpha (TNF-α) treatment. The endothelial cell proliferation, migration, permeability and tube formation were assessed by EdU assay, wound migration assay, trans-endothelial electrical resistances (TEER) assay, and capillary-like tube formation assay, respectively. In addition, the expression of relevant proteins was assessed using Western blot analysis. We confirmed that punicalagin could reduce the adhesion of human monocyte cells to HUVECs in vitro and in vivo. Further, punicalagin decreased the expression of mRNA and proteins of ICAM-1 and VCAM-1 in HUVECs. Moreover, punicalagin inhibited permeability, proliferation, migration, and tube formation in VEGF-induced HUVECs, suppressed IKK-mediated activation of NF-κB signaling in TNF-α-induced endothelial cells, and inhibited vascular endothelial growth factor receptor 2 (VEGFR2) activation and downstream p-PAK1. Our findings indicated that punicalagin might have a protective effect on HUVECs activation, which suggested that punicalagin functions through an endothelial mediated mechanism for treating various disorders such as, cancer, rheumatoid arthritis, and cardiovascular disease.

In a previous work, it was shown that punicalagin, an active ingredient of pomegranate, is able to bind to PDIA3 and inhibit its disulfide reductase activity. Here we provide evidence that punicalagin can also bind to PDIA1, the main expressed form of protein disulfide isomerase (PDI). In this comparative study, the affinity and the effect of punicalagin binding on each protein were evaluated, and a computational approach was used to identify putative binding sites. Punicalagin binds to either PDIA1 or PDIA3 with a similar affinity, but the inhibition efficacy on protein reductase activity is higher for PDIA3. Additionally, punicalagin differently affects the thermal denaturation profile of both proteins. Molecular docking and molecular dynamics simulations led to propose a punicalagin binding mode on PDIA1 and PDIA3, identifying the binding sites at the redox domains a’ in two different pockets, suggesting different effects of punicalagin on proteins’ structure. This study provides insights to develop punicalagin-based ligands, to set up a rational design for PDIA3 selective inhibitors, and to dissect the molecular determinant to modulate the protein activity.

International audience; Pomegranate industrial residues are rich in highly valuable phenolics, especially the bioactive punicalagin (PU) and ellagic acid (EA). The effect of extraction conditions on the recovery of polyphenols was investigated with special insight at the selectivity for EA and PU, along with the monitoring of sugar extraction. Macerations in ethanol and/or water, extractions by scCO2:ethanol mixtures and pressurized ethanol were compared on the basis of yields, kinetics and extract composition. High extraction yields up to 61g/100gresidue were obtained because of significant extraction of sugars evenwith CO2-based solvents. The TPC and sugar extraction yields were sensitive to the solvent polarity and pressure. Thirty-two phenolics were identified in most extracts whereas in scCO2:EtOH extracts purity of EA with respect to other phenolics was maximal, thus highlighting the selectivity of this technique. For the first time, extracts of high purity in EA and devoid of PU were produced in only one step.

Background The arthropod-borne Mayaro virus (MAYV) causes “Mayaro fever,” a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. There are currently no licensed drugs against most mosquito-transmitted viruses. Punica granatum (pomegranate) fruits cultivated in Brazil have been subjected to phytochemical investigation for the identification and isolation of antiviral compounds. In the present study, we explored the antiviral activity of pomegranate extracts in Vero cells infected with Mayaro virus. Methods The ethanol extract and punicalagin of pomegranate were extracted solely from the shell and purified by chromatographic fractionation, and were chemically identified using spectroscopic techniques. The cytotoxicity of the purified compounds was measured by the dye uptake assay, while their antiviral activity was evaluated by a virus yield inhibition assay. Results Pomegranate ethanol extract (CC50 = 588.9, IC50 = 12.3) and a fraction containing punicalagin as major compound (CC50 = 441.5, IC50 = 28.2) were shown to have antiviral activity (SI 49 and 16, respectively) against Mayaro virus, an alphavirus. Immunofluorescence analysis showed the virucidal effect of pomegranate extract, and transmission electron microscopy (TEM) revealed damage in viral particles treated with this extract. Conclusions The P. granatum extract is a promising source of antiviral compounds against the alphavirus MAYV and represents an excellent candidate for future studies with other enveloped RNA viruses. Graphical abstract

This study aimed to create nanoparticles using maltodextrin and lecithin coating materials from the extract of ellagitannins obtained from pomegranate peels. The nanoparticles were further characterized by FT-IR, SEM and TGA. The initial average molecular diameter of the ET was 47.02 ± 31.0 μm. After the nanoencapsulation process, the average molecular diameters of ETM and ETL samples were determined as 371.84 ± 229.75 nm and 339.02 ± 215.29 nm, respectively. Punicalagin A, Punicalagin B and Ellagic acid were determined as the dominant phenolics in pomegranate peels. It was observed that lecithin coated nanoparticles showed high stability with −57.60 mV zeta potential compared to maltodextrin coated ones, and had higher encapsulation efficiency in punicalagin A, punicalagin B and ellagic acid phenolics. On the other hand, maltodextrin coated samples showed higher production efficiency (86.34%) and loading capacity (57.91%) than those of lecithin. It was understood that the tested coating materials had a significant effect on the color values of the nanoparticles. In addition, a significant increase in thermal stability of nanoparticles formed with both coating materials was detected. As a result, the stability, efficiency, and thermal resistance of ellagitannins significantly increased with the applied nanoencapsulation process.

Pomegranate extract (PE) and its polyphenols have been reported to show skin protective effects but their cytoprotective effects against methylglyoxal (MGO)-induced DNA damage and cell dysfunctions are unclear. Herein, we evaluated whether PE, punicalagin (PA), ellagic acid (EA), and urolithin A (UA), can alleviate MGO-induced DNA damage in human keratinocytes. PE (50 µg/mL) and PA (50 µM) protected DNA integrity and reduced the formation of MGO-DNA adducts and tailed DNA by 60.2 and 49.7%, respectively, in HaCaT cells. PE and PA reduced MGO-induced cytotoxicity by increasing the cell viability (by 17.5 and 15.0%) and decreasing reactive oxygen species (by 28.3 and 30.0%), respectively. PE and PA also ameliorated MGO-induced cell dysfunction by restoring cell adhesion, migration, and wound healing capacity. Findings from this study provide insights into the skin protective effects of PE and its polyphenols supporting their applications as potential bioactive ingredients for cosmeceuticals.

Hyperlipidemia is closely associated with various liver diseases, and effective intervention for prevention and treatment is in great need. Here, we aim to explore the protective effects of punicalagin (PU), a major ellagitannin in pomegranate, on acute hyperlipidemia-induced hepatic lipid metabolic disorders. Male C57bl/6J mice were pretreated with 50 or 200 mg kg−1 day−1 PU for 9 days before the injection of poloxamer 407 to induce acute hyperlipidemia. PU significantly lowered lipids and liver damage markers in serum, reduced excessive lipid accumulation in the liver, attenuated hepatic oxidative stress by activating the NF-E2 related factor 2 (Nrf2)-mediated antioxidant pathway, and enhanced hepatic mitochondrial complex activities and mitochondrial DNA copy number by promoting the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis pathway. Moreover, the decreased mitochondrial fusion-related proteins were also restored by PU treatment. In vitro, PU effectively decreased triglycerides and total cholesterol levels, up-regulated Nrf2 and mitochondrial biogenesis pathways and partially restored the mitochondrial morphology in palmitic acid-treated HepG2 cells. These results suggest that PU could improve acute hyperlipidemia-induced hepatic lipid metabolic abnormalities via decreasing oxidative stress and improving mitochondrial function both in vivo and in vitro, indicating that PU might be a potential intervention for hyperlipidemia-related liver diseases.

Lung cancer is the most common cause of cancer-related deaths worldwide. Punicalagin is an ellagitannin mostly found in pomegranate husk and shows very strong antitumoral activity. The purpose of this study was to investigate the mechanism in which punicalagin acts as an antiproliferative agent on A549 cell line (adenocarcinomic human alveolar basal epithelial cells) and MRC-5 cell line (normal lung fibroblast cells). The cultured cells were treated with punicalagin at concentrations of 1-100 mu M for 24 h. For this aim, cell growth inhibition, percentage of apoptotic cells, cell cycle distribution, morphological changes, cellular and mitochondrial reactive oxygen species (ROS) production, and expression of apoptotic proteins were evaluated. Cell viability test and morphological examinations showed that punicalagin at 50 and 75 mu M concentrations exhibited toxic effect against lung cancer cells but not toxic against normal lung cells. Cytoplasmic ROS production decreased with the application of punicalagin, while the level of ROS released from mitochondria increased due to mitochondrial dysfunction. Studies of apoptosis indicated that both punicalagin concentrations induced apoptotic process in A549 cells. However, cell cycle was arrested in the G(1)/S phase after punicalagin treatment. These findings suggest that punicalagin has antiproliferative and apoptotic properties in these concentrations.

Type 2 diabetes has a series of metabolic aberrations accompanied by chronic hyperglycemia, along with various comorbidities. In recent reports, punicalagin from pomegranate has been reported to exert hypoglycemic effects against diabetes. The goal of the current research was to investigate the therapeutic effectiveness and elucidate the mechanisms of punicalagin underlying type 2 diabetes. Type 2 diabetes was induced by a high-fat diet (HFD) combined with streptozotocin (STZ) injection in C57BL/6J mice. Punicalagin was administered daily by oral gavage for 4 weeks. The results indicated that high FBG (fasting blood glucose), dyslipidemia and associated islet, liver and kidney injury were observed in the model group mice. Through metabolomics analysis, it was found that the administration of punicalagin could regulate 24 potential biomarkers and their related metabolic pathways. Moreover, the pathological changes in the liver and kidney were mainly mediated by reducing gluconeogenesis and increasing glycogenesis via stimulation of the PI3K/AKT signaling pathway and regulation of the HMGB-1/TLR4/NF-κB signaling pathway, which simultaneously interrelated to ten main pathological pathways. In addition, we confirmed the positive role of punicalagin in glucosamine-induced HepG2 cells and HG-induced HK-2 cells through related mechanistic studies in vitro. In conclusion, these findings suggested that the multi-effect and multi-target action mode of punicalagin had a significant hypoglycemic effect and a protective effect on diabetes mellitus. Punicalagin might serve as an alternative functional food or as a clinical supplemental therapy for the diabetic population to ameliorate metabolic syndrome.