Punicalagin increases follicular activation, development and activity of superoxide dismutase 1, catalase, and glutathione peroxidase 1 in cultured bovine ovarian tissues.

Context The overproduction of reactive oxygen species (ROS) during in vitro culture of ovarian tissues impairs follicular development and survival. Aims To evaluate the effects of punicalagin on the development and survival of primordial follicles, stromal cell and collagen fibres, as well as on the levels of mRNA for nuclear factor erythroid 2-related factor 2 (NRF2 ), superoxide dismutase 1 (SOD1 ), catalase (CAT ), glutathione peroxidase 1 (GPX1 ) and perirredoxin 6 (PRDX6 ), and activity of antioxidant enzymes in cultured bovine ovarian tissues. Methods Bovine ovarian cortical tissues were cultured for 6days in α-MEM+ alone or with 1.0, 10.0, or 100.0µM punicalagin at 38.5°C with 5% CO2 . Follicle morphology and growth, stromal cell density, and collagen fibres were evaluated by classical histology, while the expression of mRNA was evaluated by real-time PCR. The activity of enzymes was analysed by the Bradford method. Key results Punicalagin improved follicle survival and development, reduced mRNA expression for SOD1 and CAT , but did not influence stromal cells or collagen fibres. Punicalagin (10.0µM) increased the levels of thiol and activity of SOD1, CAT , and GPX1 enzymes. Conclusions Punicalagin (10.0µM) promotes follicle survival and development and activates SOD1, CAT , and GPX1 enzymes in bovine ovarian tissues. Implications Punicalagin improves follicle development and survival in cultured ovarian tissues.

Pentagalloyl glucose induces anti-inflammatory macrophage polarization - suppressing macrophage mediated vascular cell dysfunction and TGF-ß secretion.

Background: Pentagalloyl glucose (PGG) is a polyphenol with vasoprotective properties. Targeted delivery of PGG reversed aortic aneurysm growth in several rodent models associated with decreased number of macrophages and transforming growth factor-ß (TGF-ß) expression. Thus, we sought to determine cellular mechanisms by which PGG reduces macrophage-induced aortic pathogenicity and its relationship to TGF-ß. Methods: Using THP-1 cells, primary human aortic cells, and explanted rat aortas, we assessed the anti-inflammatory effect of PGG. Expression of pro/anti-inflammatory macrophage markers was analyzed. Adhesion of monocytes as well as oxidative stress status, viability, and TGF-ß expression after primary aortic cell exposure to macrophage-conditioned medium with and without PGG were assessed. The release of TGF-ß was also examined in elastase-treated cultured rat aortas. Results: PGG pre-treatment of human aortic cell monolayers reduced the adhesion of THP-1 monocytes. PGG enhanced the expression of anti-inflammatory markers in THP-1-derived macrophages, and increased mitochondrial reactive oxygen species as well as mitochondrial polarization. Conditioned medium from THP-1-derived macrophages induced reactive oxygen species, cell death, and TGF-ß release from human aortic cells, which was suppressed by PGG. In explanted rat aortas, PGG reduced elastase mediated TGF-ß release. Conclusions: Combining anti-inflammatory, cytotoxic, and oxidative effects, PGG has high cardiovascular therapeutic potential. We confirmed previous in vivo observations whereby PGG suppressed TGF-ß response associated with disease resolution.

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

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

Pentagalloyl Glucose (PGG) Exhibits Anti-Cancer Activity against Aggressive Prostate Cancer by Modulating the ROR1 Mediated AKT-GSK3ß Pathway.

Androgen-receptor-negative, androgen-independent (ARneg-AI) prostate cancer aggressively proliferates and metastasizes, which makes treatment difficult. Hence, it is necessary to continue exploring cancer-associated markers, such as oncofetal Receptor Tyrosine Kinase like Orphan Receptor 1 (ROR1), which may serve as a form of targeted prostate cancer therapy. In this study, we identify that Penta-O-galloyl-ß-D-glucose (PGG), a plant-derived gallotannin small molecule inhibitor, modulates ROR1-mediated oncogenic signaling and mitigates prostate cancer phenotypes. Results indicate that ROR1 protein levels were elevated in the highly aggressive ARneg-AI PC3 cancer cell line. PGG was selectively cytotoxic to PC3 cells and induced apoptosis of PC3 (IC50 of 31.64 µM) in comparison to normal prostate epithelial RWPE-1 cells (IC50 of 74.55 µM). PGG was found to suppress ROR1 and downstream oncogenic pathways in PC3 cells. These molecular phenomena were corroborated by reduced migration, invasion, and cell cycle progression of PC3 cells. PGG minimally and moderately affected RWPE-1 and ARneg-AI DU145, respectively, which may be due to these cells having lower levels of ROR1 expression in comparison to PC3 cells. Additionally, PGG acted synergistically with the standard chemotherapeutic agent docetaxel to lower the IC50 of both compounds about five-fold (combination index = 0.402) in PC3 cells. These results suggest that ROR1 is a key oncogenic driver and a promising target in aggressive prostate cancers that lack a targetable androgen receptor. Furthermore, PGG may be a selective and potent anti-cancer agent capable of treating ROR1-expressing prostate cancers.

Geraniin: A dietary ellagitannin as a modulator of signalling pathways in cancer progression.

Cancer remains a global health challenge, necessitating the exploration of novel therapeutic agents. Current treatment options are unable to overwhelm and cure the cancer burden. Hence, identifying new bioactive molecular entities with potent anticancer activity is the need of the hour. Ellagitannin Geraniin (GN) is one such evidence-based novel bioactive molecular entity (BME) available from different natural sources that can effectively combat cancer. This narrative review attempts to investigate the potential of BME-GN from 2005 to 2023 as an efficient molecular anti-cancer therapeutic against diverse cancers. We provide information on GN's pharmacological advantages, metabolite profile, and capacity to modulate multiple molecular targets involved in the hallmarks of cancer. Using the search terms "Geraniin," "Gallic acid," "Ellagitannin," "pharmacological properties," "health," "antioxidant," "apoptosis," "disease management," "anti-proliferative," "in vitro," "anti-inflammatory," "anti-angiogenic," "in vivo," and "clinical trials," We searched the scientific literature using Scopus, Web of Science, Google Scholar, and PubMed. We removed publications that included overlap or equivalent content and used the most recent review on each issue as our primary reference. From an initial pool of 430 articles, 52 studies met the search criteria. These studies collectively provide substantial in vitro, in vivo, and clinical evidence of GN's potential to combat diverse cancers. Mechanistic insights revealed its involvement in fostering apoptosis, anti-inflammatory, and modulation of key signalling pathways implicated in the hallmarks of cancer. GN's pleiotropic pharmacological and molecular therapeutic properties strongly suggest its potential as a promising anticancer agent.

Integrating Cellulose Microfibrils and Ellagitannins from Rambutan Peel with Gelatin for Production of Synergistic Biobased Hydrogels.

The pursuit of renewable and eco-friendly raw materials for biobased materials is a growing field. This study utilized ellagitannin and cellulose microfibrils derived from rambutan peel waste alongside gelatin to develop eco-conscious hydrogels. The cellulose/gelatin hydrogels were formulated in two weight ratios (0.5:1 to 1:1), and the influence of gelatin on the chemical composition and rheology was studied. Composite hydrogels, functionalized with an ellagitannin-rich extract, exhibited a remarkable enhancement of up to 14-fold in compressive strength. The hydrogels also demonstrated antimicrobial properties, reducing the Staphylococcus aureus colony count within 24 h. The hydrogel, derived from rambutan peel waste, is biocompatible and could potentially be explored for biomedical applications such as drug delivery systems, and wound dressings. This suggests that it might offer significant value for sustainable materials science, although specific applications have yet to be tested.

Effects of Camellia oleifera seed shell polyphenols and 1,3,6-tri-O-galloylglucose on androgenic alopecia via inhibiting 5a-reductase and regulating Wnt/ß-catenin pathway.

Androgenetic alopecia (AGA) is the leading cause of hair loss in adults. Its pathogenesis remains unclear, but studies have shown that the androgen-mediated 5α-reductase-AR receptor pathway and the Wnt/ß-catenin signaling pathway play significant roles. Camellia oleifera is an oil plant, and its fruits have been documented in folklore as having a hair cleansing effect and preventing hair loss. In this study, we used UPLC-Q-TOF-MS/MS to identify the structure of the substances contained in the polyphenols of Camellia oleifera seed shell. These polyphenols are mainly used for shampooing and anti-hair loss purposes. Next, we used molecular docking technology to dock 41 polyphenols and steroidal 5 alpha reductase 2 (SRD5A2). We found that the docking scores and docking sites of 1,3,6-tri-O-galloylglucose (TGG) and finasteride were similar. We constructed a mouse model of DHT-induced AGA to evaluate the effects of Camellia oleifera seed shell polyphenols (CSSP) and TGG in vivo. Treatment with CSSP and TGG alleviated alopecia symptoms and reduced DHT levels. Additionally, CSSP and TGG were able to reduce androgen levels by inhibiting the SRD5A2-AR receptor signaling pathway. Furthermore, by regulating the secretion of growth factors and activating the Wnt/ß-catenin signaling pathway, CSSP and TGG were able to extend the duration of hair growth. In conclusion, our study showed that CSSP and TGG can improve AGA in C57BL/6 J mice and reduce the effect of androgen on hair follicle through the two signaling pathways mentioned above. This provides new insights into the material basis and mechanism of the treatment of AGA by CSSP.

A serine carboxypeptidase-like acyltransferase catalyzes consecutive four-step reactions of hydrolyzable tannin biosynthesis in Camellia oleifera.

Hydrolyzable tannins (HTs), a class of polyphenolic compounds found in dicotyledonous plants, are widely used in food and pharmaceutical industries because of their beneficial effects on human health. Although the biosynthesis of simple HTs has been verified at the enzymatic level, relevant genes have not yet been identified. Here, based on the parent ion-fragment ion pairs in the feature fragment data obtained using UPLC-Q-TOF-/MS/MS, galloyl phenolic compounds in the leaves of Camellia sinensis and C. oleifera were analyzed qualitatively and quantitatively. Correlation analysis between the transcript abundance of serine carboxypeptidase-like acyltransferases (SCPL-ATs) and the peak area of galloyl products in Camellia species showed that SCPL3 expression was highly correlated with HT biosynthesis. Enzymatic verification of the recombinant protein showed that CoSCPL3 from C. oleifera catalyzed the four consecutive steps involved in the conversion of digalloylglucose to pentagalloylglucose. We also identified the residues affecting the enzymatic activity of CoSCPL3 and determined that SCPL-AT catalyzes the synthesis of galloyl glycosides. The findings of this study provide a target gene for germplasm innovation of important cash crops that are rich in HTs, such as C. oleifera, strawberry, and walnut.

Recovery of Ellagic Acid from Pomegranate Peels with the Aid of Ultrasound-Assisted Alkaline Hydrolysis.

The pomegranate processing industry generates worldwide enormous amounts of by-products, such as pomegranate peels (PPs), which constitute a rich source of phenolic compounds. In this view, PPs could be exploited as a sustainable source of ellagic acid, which is a compound that possesses various biological actions. The present study aimed at the liberation of ellagic acid from its bound forms via ultrasound-assisted alkaline hydrolysis, which was optimized using response surface methodology. The effects of duration of sonication, solvent:solid ratio, and NaOH concentration on total phenol content (TPC), antioxidant activity, and punicalagin and ellagic acid content were investigated. Using the optimum hydrolysis conditions (i.e., 32 min, 1:48 v/w, 1.5 mol/L NaOH), the experimental responses were found to be TCP: 4230 ± 190 mg GAE/100 g dry PPs; AABTS: 32,398 ± 1817 µmol Trolox/100 g dry PPs; ACUPRAC: 29,816 ± 1955 µmol Trolox/100 g dry PPs; 59 ± 3 mg punicalagin/100 g dry PPs; and 1457 ± 71 mg ellagic acid/100 g dry PPs. LC-QTOF-MS and GC-MS analysis of the obtained PP extract revealed the presence of various phenolic compounds (e.g., ellagic acid), organic acids (e.g., citric acid), sugars (e.g., fructose) and amino acids (e.g., glycine). The proposed methodology could be of use for food, pharmaceutical, and cosmetics applications, thus reinforcing local economies.

Combination of Hydrolysable Tannins and Zinc Oxide on Enterocyte Functionality: In Vitro Insights.

The management of gastrointestinal disease in animals represents a significant challenge in veterinary and zootechnic practice. Traditionally, acute symptoms have been treated with antibiotics and high doses of zinc oxide (ZnO). However, concerns have been raised regarding the potential for microbial resistance and ecological detriment due to the excessive application of this compound. These concerns highlight the urgency of minimizing the use of ZnO and exploring sustainable nutritional solutions. Hydrolysable tannins (HTs), which are known for their role in traditional medicine for acute gastrointestinal issues, have emerged as a promising alternative. This study examined the combined effect of food-grade HTs and subtherapeutic ZnO concentration on relevant biological functions of Caco-2 cells, a widely used model of the intestinal epithelial barrier. We found that, when used together, ZnO and HTs (ZnO/HTs) enhanced tissue repair and improved epithelial barrier function, normalizing the expression and functional organization of tight junction proteins. Finally, the ZnO/HTs combination strengthened enterocytes' defense against oxidative stress induced by inflammation stimuli. In conclusion, combining ZnO and HTs may offer a suitable and practical approach for decreasing ZnO levels in veterinary nutritional applications.

Gut microbiota and D-ribose mediate the anti-colitic effect of punicalagin in DSS-treated mice.

Background: Inflammatory bowel disease (IBD) is an increasing health burden worldwide. Punicalagin, a bioactive component rich in pomegranate rind, has been shown to attenuate chemical or bacteria-induced experimental colitis in mice, but whether punicalagin exerts its function through modulating gut microbiota and metabolites remains unexplored. Results: Punicalagin (100 mg per kg per day) administered orally to mice alleviated dextran-sodium sulfate (DSS)-induced colitis. Gut microbiota analyzed by 16S rRNA sequencing showed that punicalagin altered gut microbiota by increasing the Lachnospiraceae_NK4A136_group and Bifidobacterium abundance. To evaluate the effect of punicalagin-modulated microbiota and its metabolites in colitis mice, we transplanted fecal microbiota and sterile fecal filtrate (SFF) to mice treated with oral antibiotics. The results of fecal microbiota transplantation (FMT) demonstrated that punicalagin's anti-colitic effect is transferable by transplanting punicalagin-modulated gut microbiota and its metabolites. Additionally, we discovered that punicalagin-modulated sterile fecal filtrate also exhibits anti-colitis effects, as evidenced by improved intestinal barrier integrity and decreased inflammation. Subsequently, fecal metabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). The analysis revealed that punicalagin significantly increased the level of D-ribose. In vitro experiments showed that D-ribose has both anti-inflammatory and antioxidant properties. Furthermore, D-ribose significantly mitigated DSS-induced colitis symptoms in mice. Conclusions: Overall, this study demonstrated that gut microbiota and its metabolites partly mediate the protective effect of punicalagin against DSS-induced colitis in mice. D-ribose is a key metabolite that contributes to the anti-colitic effect of punicalagin in mice.

Biotransformation of camu-camu galloylated ellagitannins by Lactiplantibacillus plantarum with extracellular tannase activity.

Some strains of Lactiplantibacillus plantarum produce specific tannases that could enable the metabolism of ellagitannins into more bioavailable phenolic metabolites, thereby promoting the health effects of these polyphenols. However, the metabolic ability of these strains remains poorly understood. In this study, we analyzed the ability of broad esterase-producing (Est_1092+) and extracellular tannase-producing (TanA+) strains to convert a wide assortment of ellagitannins from camu-camu (Myrciaria dubia) fruit. To this end, forty-three strains were screened to identify and sequence (WGS) those producing Est_1092. In addition, six previously reported TanA+ strains were included in the study. Each strain (Est_1092+ or TanA+) was inoculated into a minimal culture medium supplemented with an aqueous camu-camu extract. After fermentation, supernatants were collected for semi-quantification of ellagitannins and their metabolites by mass spectrometry. For analysis, the strains were grouped according to their enzyme type and compared with an Est_1092 and TanA-lacking strain. Out of the forty-three isolates, three showed Est_1092 activity. Of the Est_1092+ and TanA+ strains, only the latter hydrolyzed the tri-galloyl-HHDP-glucose and various isomers of HHDP-galloyl-glucose, releasing HHDP-glucose and gallic acid. TanA+ strains also transformed three isomers of di-HHDP-galloyl-glucose, liberating di-HHDP-glucose and gallic acid. Overall, TanA+ strains released 3.6-4.9 times more gallic acid than the lacking strain. In addition, those exhibiting gallate decarboxylase activity pursued gallic acid metabolism to release pyrogallol. Neither Est_1092+ nor TanA+ strains transformed ellagitannin-core structures. In summary, TanA+ L. plantarum strains have the unique ability to hydrolyze a wide range of galloylated ellagitannins, releasing phenolic metabolites with additional health benefits.

Pomegranate polyphenol punicalagin as a nutraceutical for mitigating mild cognitive impairment: An overview of beneficial properties.

Dementia treatment has become a global research priority, driven by the increase in the aging population. Punicalagin, the primary polyphenol found in pomegranate fruit, exhibits a variety of benefits. Today, a growing body of research is showing that punicalagin is a nutraceutical for the prevention of mild cognitive impairment (MCI). However, a comprehensive review is still lacking. The aim of this paper is to provide a comprehensive review of the physicochemical properties, origin and pharmacokinetics of punicalagin, while emphasizing the significance and mechanisms of its potential role in the prevention and treatment of MCI. Preclinical and clinical studies have demonstrated that Punicalagin possesses the potential to effectively target and enhance the treatment of MCI. Potential mechanisms by which punicalagin alleviates MCI include antioxidative damage, anti-neuroinflammation, promotion of neurogenesis, and modulation of neurotransmitter interactions. Overall, punicalagin is safer and shows potential as a therapeutic compound for the prevention and treatment of MCI, although more rigorous randomized controlled trials involving large populations are required.

Development of apple pectin/soy protein isolate-based edible films containing punicalagin for strawberry preservation.

In this study, we developed punicalagin-loaded antimicrobial films based on soy protein isolate (SPI) and apple pectin (AP). The AP was derived from apple pomace waste while the punicalagin was obtained from pomegranate peel. Punicalagin was identified to exist in both α- and ß-isomers, with the ß-type being predominant. The composite films were characterized using scanning electron microscopy, Fourier transformed infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. Our results demonstrated that the incorporation of AP significantly enhanced the mechanical strength, heat resistance, and barrier properties of the films. Moreover, the composite films integrated with punicalagin exhibited excellent antimicrobial activities against Staphylococcus aureus (with a minimum bactericidal concentration value of 0.25 %), Escherichia coli (with a minimum bactericidal concentration value of 0.50 %), and Aspergillus niger. Finally, these antimicrobial film solutions were tested as coatings on strawberries and found to have significantly better effects on reducing weight loss, improving shelf-life, and maintaining the freshness of strawberries compared to coatings without punicalagin. The results indicate that antimicrobial coatings loaded with punicalagin hold great promise as multifunctional active packaging materials for fruit preservation.

Synthesis and Biological Activities of Scleropentaside D.

We report the first total synthesis of scleropentaside D, a unique C-glycosidic ellagitannin, from the ketal derivative of scleropentaside A employing site-selective O4-protection of C-acyl glycoside and copper-catalyzed oxidative coupling reaction of galloyl groups as the key steps. Our study confirms the proposed structure of this natural product, scleropentaside D, and demonstrates its effectiveness as an inhibitor of α-glycosidase.

Corilagin relieves atherosclerosis via the toll-like receptor 4 signaling pathway in vascular smooth muscle cells.

INTRODUCTION: Corilagin possesses a diverse range of pharmacologic bioactivities. However, the specific protective effects and mechanisms of action of corilagin in the context of atherosclerosis remain unclear. In this study, we investigated the impact of corilagin on the toll-like receptor (TLR)4 signaling pathway in a mouse vascular smooth muscle cell line (MOVAS) stimulated by oxidized low-density lipoprotein (ox-LDL). Additionally, we examined the effects of corilagin in Sprague-Dawley rats experiencing atherosclerosis. METHODS: The cytotoxicity of corilagin was assessed using the CCK8 assay. MOVAS cells, pre-incubated with ox-LDL, underwent treatment with varying concentrations of corilagin. TLR4 expression was modulated by either downregulation through small interfering (si)RNA or upregulation via lentivirus transfection. Molecular expression within the TLR4 signaling pathway was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. The proliferation capacity of MOVAS cells was determined through cell counting. In a rat model, atherosclerosis was induced in femoral arteries using an improved guidewire injury method, and TLR4 expression in plaque areas was assessed using immunofluorescence. Pathological changes were examined through hematoxylin and eosin staining, as well as Oil-Red-O staining. RESULTS: Corilagin demonstrated inhibitory effects on the TLR4 signaling pathway in MOVAS cells pre-stimulated with ox-LDL, consequently impeding the proliferative impact of ox-LDL. The modulation of TLR4 expression, either through downregulation or upregulation, similarly influenced the expression of downstream molecules. In an in vivo context, corilagin exhibited the ability to suppress TLR4 and MyD88 expression in the plaque lesion areas of rat femoral arteries, thereby alleviating the formation of atherosclerotic plaques. CONCLUSION: Corilagin can inhibit the TLR4 signaling pathway in VSMCs, possibly by downregulating TLR4 expression and, consequently, relieving atherosclerosis.

Enhancing the Bioavailability of the Ellagitannin, Geraniin: Formulation, Characterization, and in vivo Evaluation.

Geraniin (GE), an ellagitannin (ET) renowned for its promising health advantages, faces challenges in its practical applications due to its limited bioavailability. This innovative and novel formulation of GE and soy-phosphatidylcholine (GE-PL) complex has the potential to increase oral bioavailability, exhibiting high entrapment efficiency of 100.2 ± 0.8 %, and complexation efficiency of 94.6 ± 1.1 %. The small particle size (1.04 ± 0.11 µm), low polydispersity index (0.26 ± 0.02), and adequate zeta potential (-26.1 ± 0.12 mV), indicate its uniformity and stability. Moreover, the formulation also demonstrates improved lipophilicity, reduced aqueous and buffer solubilities, and better partition coefficient. It has been validated by various analytical techniques, including Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studies. Oral bioavailability and pharmacokinetics of free GE and GE-PL complex investigated in rabbits demonstrated enhanced plasma concentration of ellagic acid (EA) compared to free GE. Significantly, GE, whether in its free form or as part of the GE-PL complex, was not found in the circulatory system. However, EA levels were observed at 0.5 h after administration, displaying two distinct peaks at 2 ± 0.03 h (T1max) and 24 ± 0.06 h (T2max). These peaks corresponded to peak plasma concentrations (C1max and C2max) of 588.82 ng/mL and 711.13 ng/mL respectively, signifying substantial 11-fold and 5-fold enhancements when compared to free GE. Additionally, it showed an increased area under the curve (AUC), the elimination half-life (t1/2, el) and the elimination rate constant (Kel). The formulation of the GE-PL complex prolonged the presence of EA in the bloodstream and improved its absorption, ultimately leading to a higher oral bioavailability. In summary, the study highlights the significance of the GE-PL complex in overcoming the bioavailability limitations of GE, paving the way for enhanced therapeutic outcomes and potential applications in drug delivery and healthcare.

Heterogeneity of transport and metabolism of Tormentillae rhizoma constituents across human intestinal epithelium cellular model.

Tormentilla erecta (L.) Raeusch is a widespread plant in Europe and Western Asia. Its rhizomes (Tormentilae rhizoma) are the main ingredient of herbal alcoholic beverages and can be used as a natural preservative in beer production. Apart from its unique taste qualities, therapeutic properties in gastrointestinal tract ailments are attributed to the tincture obtained from Tormentillae rhizoma. The presented research aimed to determine the mutual relationship between the components of Tormentillae tincture, present in popular alcoholic beverages, and intestinal epithelium (Caco-2 cell monolayers). A comprehensive qualitative and quantitative analysis of the tincture was performed, including the determination of condensed and hydrolyzable tannins as well as triterpenoids (UHPLC-DAD-MS/MS). Incubation of the tincture with Caco-2 monolayers has shown that only triterpenes pass through the monolayer, while condensed tannins are mainly bound to the monolayer surface. Ellagic acid derivatives were the only components of the Tormentillae tinctura being metabolized by cell monolayers to the compounds not previously described in the literature, which may be crucial in the treatment of intestinal diseases with inflammatory background.

Punicalagin Ameliorates Diabetic Liver Injury by Inhibiting Pyroptosis and Promoting Autophagy via Modulation of the FoxO1/TXNIP Signaling Pathway.

Diabetic liver injury (DLI) is one of the complications of diabetes mellitus, which seriously jeopardizes human health. Punicalagin (PU), a polyphenolic compound mainly found in pomegranate peel, has been shown to ameliorate metabolic diseases such as DLI, and the mechanism needs to be further explored. In this study, a HFD/STZ-induced diabetic mouse model is established to investigate the effect and mechanism of PU on DLI. The results show that PU intervention significantly improves liver histology and serum biochemical abnormalities in diabetic mice, significantly inhibits the expression of pyroptosis-related proteins such as NLRP3, Caspase1, IL-1ß, and GSDMD in the liver of diabetic mice, and up-regulated the expression of autophagy-related proteins. Meanwhile, PU treatment significantly increases FoxO1 protein expression and inhibits TXNIP protein expression in the liver of diabetic mice. The above results are further verified in the HepG2 cell injury model induced by high glucose. AS1842856 is a FoxO1 specific inhibitor. The intervention of AS1842856 combined with PU reverses the regulatory effects of PU on pyroptosis and autophagy in HepG2 cells. In conclusion, this study demonstrates that PU may inhibit pyroptosis and upregulate autophagy by regulating FoxO1/TXNIP signaling, thereby alleviating DLI.

Changes in phenolic compounds of Phyllanthus emblica juice during different storage temperature and pH conditions.

The aim of this experiment was to investigate the effect of storage temperature and pH on phenolic compounds of Phyllanthus emblica juice. Juice was stored at different temperatures and pH for 15 days and sampled on 2-day intervals. The browning index (BI, ABS420 nm), pH, centrifugal precipitation rate (CPR), and phenolic compounds were evaluated. The results showed 4°C and pH 2.5 could effectively inhibit browning and slow down pH drop of P. emblica juice. The result of orthogonal partial least square-discriminant analysis showed P. emblica juice stored at 4°C and pH 2.5 still had a similar phenolic composition, but at 20°C, 37°C, and pH 3.5, the score plots were concentrated only in the first 3 days. Additionally, gallic acid (GA) and ellagic acid (EA) were screened out to be the differential compounds for browning of P. emblica juice. The contents of GA, epigallocatechin (EGC), corilagin (CL), gallocatechin gallate (GCG), chebulagic acid (CA), 1,2,3,4,6-O-galloyl-d-glucose (PGG), and EA were more stable at 4°C and pH 2.5. Overall, during storage at 4°C and pH 2.5, it could inhibit the increase of GA and EA and decrease of CL, GCG, CA, and PGG, whereas EGC did not show significant difference between storage conditions. The CPR was higher at 4°C, while pH 2.5 could reduce the CPR. In conclusion, in order to maintain stability of phenolic compounds and extended storage period, the P. emblica juice could be stored at low temperature and adjust the pH to increase the stability of juice system.