Valoneic Acid Dilactone Research Articles

Antiplasmodial Activity of Hydroalcoholic Extract from Jucá (Libidibia ferrea) Pods.

Malaria is an infectious and parasitic disease caused by protozoa of the genus Plasmodium, which affects millions of people in tropical and subtropical areas. Recently, there have been multiple reports of drug resistance in Plasmodium populations, leading to the search for potential new active compounds against the parasite. Thus, we aimed to evaluate the in vitro antiplasmodial activity and cytotoxicity of the hydroalcoholic extract of Jucá (Libidibia ferrea) in serial concentrations. Jucá was used in the form of a freeze-dried hydroalcoholic extract. For the cytotoxicity assay, the(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method with the WI-26VA4 human cell line was used. For the antiplasmodial activity, Plasmodium falciparum synchronized cultures were treated with serial concentrations (0.2 to 50 μg/mL) of the Jucá extract. In terms of the chemical composition of the Jucá extract, gas chromatography coupled to mass spectrometry measurements revealed the main compounds as ellagic acid, valoneic acid dilactone, gallotannin, and gallic acid. The Jucá hydroalcoholic extract did not show cytotoxic activity per MTT, with an IC50 value greater than 100 µg/mL. Regarding the antiplasmodial activity, the Jucá extract presented an IC50 of 11.10 µg/mL with a selective index of nine. Because of its antiplasmodial activity at the tested concentrations and low toxicity, the Jucá extract is presented as a candidate for herbal medicine in the treatment of malaria. To the best of our knowledge, this is the first report of antiplasmodial activity in Jucá.

In vitro and in vivo glycemic responses and antioxidant potency of acorn and chickpea fortified gluten-free breads

Gluten-free (GF) breads, based on rice flour and corn starch (50:50), were fortified with a mixture of acorn flour (ACF) - chickpea flour (CPF) at 30% substitution level of corn starch (i.e., rice flour:corn starch:ACF-CPF 50:20:30) using different flour blends of ACF:CPF at weight ratios of 5:25, 7.5:22.5, 12.5:17.5, and 20:10 in order to improve the nutritional quality and antioxidant potential as well as the glycemic responses of the GF breads; a control GF bread with rice flour:corn starch 50:50 ratio was also prepared. ACF was richer in total phenolic content than CPF, whereas CPF was characterized by higher amounts of total tocopherols and lutein compared to ACF. For both ACF and CPF as well as the fortified breads, the most abundant phenolic compounds were gallic (GA) and ellagic (ELLA) acids as found by HPLC-DAD analysis, while a hydrolysable tannin, valoneic acid dilactone, was also identified and quantified by HPLC-DAD-ESI-MS in high amount in the ACF-GF bread having the highest level of ACF (ACF:CPF 20:10), even though it seemed to decompose during breadmaking, possibly into GA and ELLA. Therefore, the inclusion of these two raw materials as ingredients in GF bread formulations resulted in baked products with enhanced concentrations of such bioactive compounds and higher antioxidant activities, as indicated by three different assays (DPPH, ABTS and FRAP). The extent of glucose release, as evaluated by an in vitro enzymic assay, was negatively correlated (r = −0.96; p = 0.005) with the level of added ACF, and was significantly reduced for all ACF-CPF fortified products when compared with their non-fortified GF counterpart. Furthermore, the GF bread containing a flour mixture of ACP:CPF at a weight ratio of 7.5:22.5, was subjected to an in vivo intervention protocol to assess the glycemic response when consumed by 12 healthy volunteers; in this case, white wheat bread was used as reference food. The glycemic index (GI) of the fortified bread was significantly lower compared to the control GF bread (97.4 versus 159.2, respectively), which along with its lower amount of available carbohydrates and the higher level of dietary fibers, resulted in a significantly reduced glycemic load (7.8 versus 18.8 g per serving of 30 g). The present findings underlined the effectiveness of acorn and chickpea flours in improving the nutritional quality and glycemic responses of fortified GF breads with these flours.

Gastroprotective effect methanol extract of Caesalpinia coriaria pods against indomethacin- and ethanol-induced gastric lesions in Wistar rats

Ethnopharmacological relevanceCaesalpinia coriaria (Jacq.) Willd is widely used as a traditional medinal plant in Mexico for protective and healing purposes and the treatment of gastrointestinal diseases. Aim of the studyTo investigate the gastroprotective effect of extract of Caesalpinia coriaria pods against ethanol-induced and indomethacin-induced gastric lesion models, its anti-inflammatory and antioxidative activities, and its main compounds through LC-MS analysis. Materials and methodsMale Wistar rats were orally administered a methanol extract obtained from the pods of C. coriaria at doses of 10, 30, 100, and 300 mg/kg prior to inducing gastric lesions with ethanol or indomethacin. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations. Determination of prostaglandin E2 (PGE2), alpha tumor necrosis factor (TNF-α), leukotriene B4 (LTB4), nitrites/nitrates, superoxide dismutase (SOD), and H2S gastric levels were investigated. Its main compounds of the active extract through LC-MS analysis. ResultsPhenolic compounds were identified as major components of methanol extract. LC-MS analysis identified 15 constituents, and the significant compounds were gallic acid, 3-O-galloylquinic acid, digalloylglucose, tetragalloylglucose, valoneic acid dilactone, pentagalloylglucose, digalloylshikimic acid, and ellagic acid. Pretreatment with the extract at doses of 100 and 300 mg/kg significantly reduced gastric ulcer lesions in both models. Compared with the reference drugs (omeprazole or ranitidine, respectively), no significant difference was found (p < 0.05). The extract's gastroprotective effect was accompanied by significant decreases in leukocyte recruitment, and gastric levels of TNF-α and LTB4 by two to fourfold (p < 0.05). Also, gastric levels of PGE2 gastric levels were maintained and the antioxidant enzyme activities of SOD and nitrate/nitrite in the gastric tissue were improved (p < 0.05). The LC-MS analysis indicated the presence of hydrolyzable tannins (mainly gallic acid derivatives). ConclusionThe results suggest that the gastroprotective effect of the methanol extract of C. coriaria pods occurs through anti-inflammatory, antioxidant, and NO modulation properties, and gallic acid derivatives may be the main possible compounds responsible for its actions.

Study of the antioxidant activity of Pistacia atlantica Desf. Gall extracts and evaluation of the responsible compounds

Defensive gall traits against natural enemies, such as predators and parasitoids, attracted much attention of ecologists and evolutionary biologists. To our knowledge, naturally occurring antioxidant compounds present in Pistacia atlantica Desf. Galls have not yet been reported and characterized. The objective of this study is to evaluate the effects of the harvest period and plant gender on these antioxidant activities. Furthermore, peaks present in chromatographic fingerprints, probably showing significant antioxidant activities, were identified. Three antioxidant assays, 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2 azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging besides the ferric reducing antioxidant power (FRAP), were applied to determine the total antioxidant activity in galls from both genders of Pistacia atlantica. Fingerprints of ten P. atlantica gall extracts were obtained by Ultra Performance Liquid Chromatography (UPLC). Extensive pre-treatment of the data and a linear multivariate calibration technique, Partial Least Squares (PLS), were used for model construction. Our findings highlighted that gender and harvest period affected the antioxidant activities. Major peaks, potentially influencing the antioxidant activity of the samples, were indicated by studying the regression coefficients of the PLS models. Individual antioxidant compounds of P. atlantica galls were identified by UPLC coupled to a hybrid quadrupole orthogonal time-of-flight mass spectrometer (Q-TOF/MS). The phenolic compounds methyl gallate and valoneic acid dilactone were considered to be important antioxidants in the FRAP and scavenging ABTS assays, while quinic acid showed to be the main component influencing the antioxidant activity measured with the DPPH method. The findings of the present study suggest that P. atlantica gall might be used as an accessible source of natural antioxidants and for the treatment of diseases resulting from oxidative stress.

Pharmacological investigation of antioxidant and anti-inflammatory activities of leaves and branches extracts from Plinia cauliflora (Jaboticaba)

Ethnopharmacological relevanceAmong all native Brazilian plant species, Plinia cauliflora (DC.) Kausel (Jaboticaba), is well known for producing “superfruits”, due to their high phenolic content and antioxidant property. The fruit has astringent characteristics, and it is popularly known for the treatment of diarrhea, rash, and intestinal inflammation. However, there are only a few studies on the use of leaves and branches of this species in the literature, mainly to treat oxidative stress and inflammation. Aim of the studyThe present study aimed to investigate the antioxidant and anti-inflammatory potential of leaves and branches extracts from P. cauliflora. Material and methodsThe phytochemical analysis of P. cauliflora extracts was performed by the total phenolic, flavonoid, and tannin dosage method. Moreover, the compounds were identified by HPLC-MS-Q-TOF. Antioxidant capacity was determined by DPPH, β-carotene/linoleic acid system, MDA formation, and phosphomolybdenum assays. In vitro and in vivo anti-inflammatory activities of P. cauliflora were evaluated by the reduction of nitric oxide in the J774A.1 cell line and inhibition of ear edema in mice, respectively. ResultsThe ethanolic extract of the leaves exhibited greater flavonoid content whereas the ethanolic extract of the branches showed higher tannins content. Twenty-two and seventeen compounds were identified by HPLC-MS-Q-TOF in the leaves and branches, respectively, being tellimagrandin I, castalagin, and valoneic acid dilactone reported for the first time in P. cauliflora. The antioxidant potential of extracts was confirmed through different oxidation pathways from oxidizing radicals, which might be related to the presence of phenolic compounds. For the anti-inflammatory assay, the leaves and branches extracts showed promising results, with a reduction of nitric oxide ear edema inhibition around 95% and 80%, respectively. ConclusionsHerein, the great biological potential of leaves and branches extracts from P. cauliflora was highlighted. These parts of the plant are underused and poorly reported in the literature, especially for the antioxidant and anti-inflammatory activities.

Two new C-glycosidic ellagitannins and accompanying tannins from Lawsonia inermis leaves and their cytotoxic effects

Investigation on tannins having antitumor properties led to the isolation of two new C-glycosidic ellagitannins (1 and 2) along with seven known ellagitannins (3–9) and a related polyphenolic constituent (10) from Lawsonia inermis leaves. Our intensive HRESIMS, 1D and 2D NMR, and ECD spectroscopic studies of new tannins have shown that one (1) has a monomer structure of C-glycosidic tannin, and the other (2) has a dimeric structure of 2,3-O-hexahydroxydiphenoyl glucopyranose and a C-glycosidic tannin. Among the known compounds, one (3) is a C-glycosidic tannin that was isolated first of all from nature, five were C-glycosidic tannins, vescalagin (4), 1-O-methylvescalagin (5), castalagin (6), stachyurin (7), and casuarinin (8), and one was an O-glycosidic ellagitannin, tellimagrandin II (9). The remaining phenolic constituent from the leaves was identified as valoneic acid dilactone (10). The ellagitannins 1, and 3–9 demonstrated noticeable cytotoxicity on human oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9–22), and lower effects on human oral normal cells (HGF, HPC, and HPLF). Tellimagrandin II (9) had the highest tumor-specific cytotoxicity, and also cleaved poly (ADP-ribose) polymerase 1 in HSC-2 cells. These findings showed that L. inermis ellagitannins may be a candidate for the production of anti-oral cancer materials.

Advanced characterization of polyphenols from Myrciaria jaboticaba peel and lipid protection in in vitro gastrointestinal digestion

Ultrasound-assisted and solvent extractions resulted in similar levels of hydrolyzable tannins (10.3–6.0 mg/g), anthocyanins (7.8–10.2 mg/g) and flavonols (0.24–0.32 mg/g) for dried Myrciaria jaboticaba peel (DJP). Ultrasound was efficient for the extraction of poorly soluble hydrolyzable tannins but affected the stability of anthocyanins and flavonols. UPLC-DAD-MSn allowed the identification of 44 hydrolyzable tannins as single and mixed hexosides bearing galloyl, HHDP and tergalloyl units. Twelve mixed HHDP-galloylgluconic acids and tergalloylated hexosides were newly discovered in this work. Acid hydrolysis of both ultrasonic extract and DJP yielded five major compounds, i.e. gallic acid, ellagic acid, gallic acid-C-hexoside, valoneic acid dilactone and sanguisorbic acid dilactone and pointed to higher contents in hydrolyzable tannins than by summing individual polyphenols after UPLC. Last, cyanidin-3-O-glucoside and hydrolyzable tannins from the ultrasonic extract inhibited lipid peroxidation of a Western type meal in in vitro digestion, suggesting a health benefit for these jabuticaba polyphenols.

Barricyclin D1-a dimeric ellagitannin with a macrocyclic structure-and accompanying tannins from Barringtonia racemosa.

Our examination of high molecular weight polyphenolic constituents in the leaves of Barringtonia racemosa of the family Lecythidaceae uncovered 5 previously undescribed ellagitannins. One, barringtin M1 (1), among them was a hydrolysable tannin monomer, while remaining 4, barringtins D1 (2), D2 (3), D3 (4), and barricyclin D1 (5), were all dimers. Barricyclin D1 had a first macrocyclic structure formed from casuarictin (6) and tellimagrandin I (7), and the other ellagitannins had structures related to 5. Two additional known phenolics, valoneic acid dilactone (8) and schimawalin A (9), were also isolated from the leaves. These results suggested that the leaves of B. racemosa are a natural resource rich in hydrolysable tannin oligomers.

The determination of the phytochemical composition of the Altabor substance

The development of medicines based on alder cone extracts led to the introduction of Altan and Altabormedicines into medical practice. The technology of extraction cake from cones has made it possible to obtain extracts with different therapeutic properties.Aim. To develop an effective method for studying the qualitative composition of the Altabor substance anddetermine the quantitative content of its components.Results and discussion. The Altabor substance is a complex mixture of ellagitannins containing more than 70 components. The main components of the extract (or their isomers) were determined by mass spectrometry and by comparing the retention times with the literature data. Gallic, ellagic, valoneic acids dilactone were conclusively determined by adding reference standards of these acids to the extract. The substance contains the following compounds: 2,3-hexahydroxydiphenoyl-(α/β)-glucose tr1 = 0.55 min, tr2 = 0.89 min (α and β isomers), 4,6-O-[(S)-valeonyl]-D-glucose (isomer) tr = 0.64 min, gallic acid tr = 1.198 min, pedunculagin tr1 = 3.63 min, tr2 = 4.62 min(α and β isomers), proecoxin A (isomer) tr = 4.78 min, valoneic acid dilactone tr = 6.19 min, ellagic acid pentoside (isomer) tr = 7.07 min, ellagic acid tr = 7.335 min.Experimental part. The composition analysis was performed using an Agilent 1200 chromatograph with a UV detector, a G6140 mass detector, an Alltech 3300 light scattering detector (ELSD), as well as the Agilent ChemStation Rev.B.04.03 software. The molecular weights of the compounds in the extract were determined using the method of mass spectrometry of ESI-electrospray ionization. The determination of the components was performed using an ultraviolet detector at a wavelength of 280 nm. The column was Rapid Resolution HT Cartige, 4.6 × 30 mm, 1.8 μm, Zorbax SB-C18.Conclusions. A new effective method of analysis of the Altabor substance has been developed; it allowsdetermining the qualitative and quantitative content of its structural components. The method gives the possibility to control the process of obtaining the Altabor substance, study the dependence of its composition on the conditions of its obtaining, batch number, place, time of the natural raw material collection, and study the composition of other pharmaceutical substances, the plant raw material containing tannins. The advantage of the method isthe short time (up to 10 min) of analysis using high-performance liquid chromatography at high resolution.Key words: gallotannins; ellagitannins; Altabor; chemical composition; structure; HPLC (high-performance liquid chromatography)

Combined in silico and in vitro studies to identify novel antidiabetic flavonoids targeting glycogen phosphorylase

Novel pharmacological strategies for the treatment of diabetic patients are now focusing on inhibiting glycogenolysis steps. In this regard, glycogen phosphorylase (GP) is a validated target for the discovery of innovative antihyperglycemic molecules. Natural products, and in particular flavonoids, have been reported as potent inhibitors of GP at the cellular level. Herein, free-energy calculations and microscale thermophoresis approaches were performed to get an in-depth assessment of the binding affinities and elucidate intermolecular interactions of several flavonoids at the inhibitor site of GP. To our knowledge, this is the first study indicating genistein, 8-prenylgenistein, apigenin, 8-prenylapigenin, 8-prenylnaringenin, galangin and valoneic acid dilactone as natural molecules with high inhibitory potency toward GP. We identified: i) the residues Phe285, Tyr613, Glu382 and/or Arg770 as the most relevant for the binding of the best flavonoids to the inhibitor site of GP, and ii) the 5-OH, 7-OH, 8-prenyl substitutions in ring A and the 4′-OH insertion in ring B to favor flavonoid binding at this site.Our results are invaluable to plan further structural modifications through organic synthesis approaches and develop more effective pharmaceuticals for Type 2 Diabetes treatment, and serve as the starting point for the exploration of food products for therapeutic usage, as well as for the development of novel bio-functional food and dietary supplements/herbal medicines.

A phenolic small molecule inhibitor of RNase L prevents cell death from ADAR1 deficiency

The oligoadenylate synthetase (OAS)-RNase L system is an IFN-inducible antiviral pathway activated by viral infection. Viral double-stranded (ds) RNA activates OAS isoforms that synthesize the second messenger 2-5A, which binds and activates the pseudokinase-endoribonuclease RNase L. In cells, OAS activation is tamped down by ADAR1, an adenosine deaminase that destabilizes dsRNA. Mutation of ADAR1 is one cause of Aicardi-Goutières syndrome (AGS), an interferonopathy in children. ADAR1 deficiency in human cells can lead to RNase L activation and subsequent cell death. To evaluate RNase L as a possible therapeutic target for AGS, we sought to identify small-molecule inhibitors of RNase L. A 500-compound library of protein kinase inhibitors was screened for modulators of RNase L activity in vitro. We identified ellagic acid (EA) as a hit with 10-fold higher selectivity against RNase L compared with its nearest paralog, IRE1. SAR analysis identified valoneic acid dilactone (VAL) as a superior inhibitor of RNase L, with 100-fold selectivity over IRE1. Mechanism-of-action analysis indicated that EA and VAL do not bind to the pseudokinase domain of RNase L despite acting as ATP competitive inhibitors of the protein kinase CK2. VAL is nontoxic and functional in cells, although with a 1,000-fold decrease in potency, as measured by RNA cleavage activity in response to treatment with dsRNA activator or by rescue of cell lethality resulting from self dsRNA induced by ADAR1 deficiency. These studies lay the foundation for understanding novel modes of regulating RNase L function using small-molecule inhibitors and avenues of therapeutic potential.

A mass spectrometry and 1H NMR study of hypoglycemic and antioxidant principles from a Castanea sativa tannin employed in oenology

The ethanol extract of the commercial tannin Tan’Activ C, (from Castanea sativa wood), employed in oenology, was subjected to chromatography on XAD-16 affording fractions X1–X5, evaluated for total phenols content (GAE), antioxidant activity (DPPH, ORAC), and hypoglycemic activity (α-glucosidase inhibition). Fraction X3 showed GAE, radical scavenging activity, and α-glucosidase inhibition higher than those of the Castanea sativa extract, and was subjected to chromatography on Sephadex LH-20 to obtain fractions S1–S7, analyzed by HPLC/ESI-MS/MS and 1H NMR to identify the main active constituents. In fractions with higher antioxidant activity, gallic acid (4), grandinin (5), valoneic acid dilactone (9), 1,2,3-tri-O-galloyl-β-glucose (14), 3,4,6-tri-O-galloyl-β-glucose (15) and galloyl derivative of valoneic acid dilactone (21) were identified as the major constituents. The highest hypoglycemic activity was found in fractions S6 and especially S7; the major constituents of these fractions are valoneic acid dilactone (9), three tetragalloyl glucose isomers (16–18) and 1,2,3,4,6-penta-O-galloyl-β-glucose (23), previously reported as α-glucosidase inhibitors.

Effects of two different drying methods (freeze-drying and hot air-drying) on the phenolic and carotenoid profile of ‘Ataulfo’ mango by-products

The agro-industrial processing of mango generates high amounts of by-products, like peels and paste, that are commonly discarded. These are potential sources of bioactive ingredients, such as phenolic compounds and carotenoids, that can be used to supplement other edible products to increase their nutritional value. In order to be successful in this regard, the processing methods used must avoid losses of the compounds of interest. The objective of this study was to identify the effects of freeze-drying (frozen 24 h at − 80 °C, freeze dried 48 h at − 50 °C, 4.00 Pa) and hot air-drying (convective hot air at 60 °C) on the profile and concentration of phenolic compounds and carotenoids, using sensitive chromatographic analyses. Our data showed that the total phenolic concentration, and that of the most abundant compounds (mangiferin and valoneic acid dilactone), were unaffected by drying method. Conversely, freeze-dried paste had greater carotenoid concentration than peel, while hot air-dried peel had greater carotenoid concentration than paste (main carotenoids: all-trans-β-carotene, 9-cis-β-carotene, all-trans-lutein, and 13-cis-β-cryptoxanthin). We concluded that carotenoids from mango peel and paste were more sensitive to drying method than phenolic compounds, and the effects on each by-product were in function of the food matrix and method used. By choosing the most adequate drying method, mango by-products can be sources of bioactive compounds to produce functional foods or beverages.

Integrative Analysis Based on HPLC-DAD-MS/MS and NMR of Bertholletia excelsa Bark Biomass Residues: Determination of Ellagic Acid Derivatives

Bertholletia excelsa Bonpl. (Lecythidaceae) is a South American tree worldwide known for providing the Brazil nuts. In the Amazon Region, B. excelsa is found in monocultures, integrating agroforestries and providing raw materials for food and timber industries. Through the application of an integrative analysis based on high-performance liquid chromatography coupled with diode array detector and tandem mass spectrometry (HPLC-DAD-MS/MS) and nuclear magnetic resonance (NMR) techniques, the present study showed that B. excelsa bark biomass residues contain large quantities of ellagic acid (EA) and its derivatives. Qualitatively, five compounds were characterized for the first time in this species. Quantitations were carried out to determine the total amount of these compounds in outer and inner bark tissues. A total of 4.96 and 44.09 g of EA derivatives per kg of dry residues was determined for the outer and inner barks, respectively. Among the EA derivatives, eschweilenol C, ellagic acid and valoneic acid dilactone were the main compounds. These results pointed B. excelsa barks as a valuable biomass residue with potential to be source of health-promoting compounds. Therefore, a potential raw material as source of valuable bioactive phenolic compounds is described herein.

Punica granatum peel extracts: HPLC fractionation and LC MS analysis to quest compounds having activity against multidrug resistant bacteria

BackgroundMedicinal plants are rich source of traditional herbal medicine around the globe. Most of the plant’s therapeutic properties are due to the presence of secondary bioactive compounds.MethodsThe present study analyzed the High Pressure Liquid Chromatography (HPLC) fractions of Puncia granatum (peel) extracts (aqueous, chloroform, ethanol and hexane) against multidrug resistant bacterial pathogens (Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus). All the fractions having antibacterial activity was processed for bioactive compounds identification using LC MS/MS analysis.ResultsAmong total HPLC fractions (n = 30), 4 HPLC fractions of P. granatum (peel) showed potential activity against MDR pathogens. Fraction 1 (F1) and fraction 4 (F4) collected from aqueous extract showed maximum activity against P. aeruginosa. Fraction 2 (F2) of hexane showed antibacterial activity against three pathogens, while ethanol F4 exhibited antibacterial activity against A. baumannii. The active fractions were processed for LC MS/MS analysis to identify bioactive compounds. Valoneic acid dilactone (aqueous F1 and F4), Hexoside (ethanol F4) and Coumaric acid (hexane F2) were identified as bioactive compounds in HPLC fractions.ConclusionPuncia granatum peel extracts HPLC fractions exhibited potential inhibitory activity against MDR bacterial human pathogens. Several bioactive compounds were identified from the HPLC fractions. Further characterization of these compounds may be helpful to conclude it as therapeutic lead molecules against MDR pathogens.

Walnut Polyphenol Extract Attenuates Immunotoxicity Induced by 4-Pentylphenol and 3-methyl-4-nitrophenol in Murine Splenic Lymphocyte.

4-pentylphenol (PP) and 3-methyl-4-nitrophenol (PNMC), two important components of vehicle emissions, have been shown to confer toxicity in splenocytes. Certain natural products, such as those derived from walnuts, exhibit a range of antioxidative, antitumor, and anti-inflammatory properties. Here, we investigated the effects of walnut polyphenol extract (WPE) on immunotoxicity induced by PP and PNMC in murine splenic lymphocytes. Treatment with WPE was shown to significantly enhance proliferation of splenocytes exposed to PP or PNMC, characterized by increases in the percentages of splenic T lymphocytes (CD3+ T cells) and T cell subsets (CD4+ and CD8+ T cells), as well as the production of T cell-related cytokines and granzymes (interleukin-2, interleukin-4, and granzyme-B) in cells exposed to PP or PNMC. These effects were associated with a decrease in oxidative stress, as evidenced by changes in OH, SOD, GSH-Px, and MDA levels. The total phenolic content of WPE was 34,800 ± 200 mg gallic acid equivalents/100 g, consisting of at least 16 unique phenols, including ellagitannins, quercetin, valoneic acid dilactone, and gallic acid. Taken together, these results suggest that walnut polyphenols significantly attenuated PP and PNMC-mediated immunotoxicity and improved immune function by inhibiting oxidative stress.

Antihypertensive Effect of Valoneic Acid Dilactone on Fludrocortisone Induced Hypertensive Rats

Antihypertensive Effect of Valoneic Acid Dilactone on Fludrocortisone Induced Hypertensive Rats

Validated Method for the Characterization and Quantification of Extractable and Nonextractable Ellagitannins after Acid Hydrolysis in Pomegranate Fruits, Juices, and Extracts.

Pomegranates are one of the main highly valuable sources of ellagitannins. Despite the potential health benefits of these compounds, reliable data on their content in pomegranates and derived extracts and food products is lacking, as it is usually underestimated due to their complexity, diversity, and lack of commercially available standards. This study describes a new method for the analysis of the extractable and nonextractable ellagitannins based on the quantification of the acid hydrolysis products that include ellagic acid, gallic acid, sanguisorbic acid dilactone, valoneic acid dilactone, and gallagic acid dilactone in pomegranate samples. The study also shows the occurrence of ellagitannin C-glycosides in pomegranates. The method was optimized using a pomegranate peel extract. To quantify nonextractable ellagitannins, freeze-dried pomegranate fruit samples were directly hydrolyzed with 4 M HCl in water at 90 °C for 24 h followed by extraction of the pellet with dimethyl sulfoxide/methanol (50:50, v/v). The method was validated and reproducibility was assessed by means of an interlaboratory trial, showing high reproducibility across six laboratories with relative standard deviations below 15%. Their applicability was demonstrated in several pomegranate extracts, different parts of pomegranate fruit (husk, peels, and mesocarp), and commercial juices. A large variability has been found in the ellagitannin content (150-750 mg of hydrolysis products/g) and type (gallagic acid/ellagic acid ratios between 4 and 0.15) of the 11 pomegranate extracts studied.

Aldose reductase and protein tyrosine phosphatase 1B inhibitory active compounds from Syzygium cumini seeds

Context: Syzygium cumini (L.) Skeels (Myrtaceae), commonly known as jamun, is an Indian plant, traditionally well known for its medicinal properties including antidiabetic activity.Objective: To isolate the antidiabetic compounds from Syzygium cumini seeds and evaluate their activity using aldose reductase (AR) and protein-tyrosine phosphatase 1B (PTP1B) inhibition assays.Materials and methods: The dried seeds were extracted with methanol and partitioned with ethyl acetate, butanol, and water. The extracts were screened for antidiabetic activity at a concentration of 100 µg/mL using in vitro AR and PTP 1B inhibition assays.Results and discussion: The highly enriched fractions obtained from broad ethyl acetate fraction yielded maslinic acid (1), 5-(hydroxymethyl) furfural (2), gallic acid (3), valoneic acid dilactone (4), rubuphenol (5), and ellagic acid (6). Structures were elucidated by 1H-NMR and 13C-NMR. The initial ethyl acetate fraction showed AR inhibitory activity with the IC50 value of 2.50 μg/mL and PTP1B enzyme inhibition with the IC50 value of 26.36 μg/mL. Compounds 3, 4, 5, and 6 were found to inhibit AR with IC50 values of 0.77, 0.075, 0.165, and 0.12 μg/mL while the compounds 4, 5, and 6 inhibited PTP1B with IC50 values of 9.37, 28.14, and 25.96 μg/mL, respectively.Conclusion: The results of this study demonstrate that the isolated constituents show promising in vitro antidiabetic activity and, therefore, can be candidates for in vivo biological screening using relevant models to ascertain their antidiabetic activity.

Isolation of Antidiabetic Principle from Fruit Rinds ofPunica granatum

Present study was aimed to isolate and evaluate the antidiabetic activity of phytoconstituents from fruit rinds of Punica granatum. With the above objectives Valoneic acid dilactone (VAD) was isolated from methanolic fruit rind extracts of Punica granatum (MEPG) and confirmed by 1H-NMR, 13C-NMR, and mass spectral data. Antidiabetic activity was evaluated by Aldose reductase, α-amylase and PTP1B inhibition assays in in vitro and Alloxan-induced diabetes in rats was used as an in vivo model. In bioactivity studies, MEPG and VAD have showed potent antidiabetic activity in α-amylase, aldose reductase, and PTP1B inhibition assays with IC50 values of 1.02, 2.050, 26.25 μg/mL and 0.284, 0.788, 12.41 μg/mL, respectively. Furthermore, in alloxan-induced diabetes model MEPG (200 and 400 mg/kg, p.o.) and VAD (10, 25, and 50 mg/kg, p.o.) have showed significant and dose dependent antidiabetic activity by maintaining the blood glucose levels within the normal limits. Inline with the biochemical findings histopathology of MEPG (200 and 400 mg/kg, p.o.), VAD (10, 25, and 50 mg/kg, p.o.), and glibenclamide (10 mg/kg, p.o.) treated animals showed significant protection against alloxan-induced pancreatic tissue damage. These findings suggest that MEPG and VAD possess significant antidiabetic activity in both in vitro and in vivo models.