Ellagic acid inhibits gastric cancer cells by modulating oxidative stress and inducing apoptosis

Objective:To evaluate the anticancer effect of ellagic acid on gastric cancer cells.Methods:MTT assay was used to evaluate the effect of ellagic acid at different concentrations(0.5-100μg/mL)on gastric cancer AGS cells.RT-qPCR and Western blot analyses were applied to assess apoptosis(BCL-2,CASP-3,and BAX)and autophagy(LC3,ATG5,and BECN1)in AGS cells treated with ellagic acid.The expression of invasion-related markers including TP53,CDKN2A,and PTEN was determined.In addition,cell cycle markers including cyclin A,B,D,and E were measured by ELISA.Oxidative stress markers were evaluated using spectrophotometry.Results:Ellagic acid inhibited the proliferation of AGS cells in a concentration-and time-dependent manner.The expression of BCL-2 was significantly decreased(P<0.05)and CASP-3 and BAX were markedly increased(P<0.01)in AGS cells treated with ellagic acid.However,this compound induced no significant changes in the expression levels of LC3,ATG5,and BECN1(P>0.05).Moreover,the oxidative stress markers including SOD,TAC,and MDA were increased by ellagic acid(P<0.01).Conclusions:Ellagic acid can inhibit cell proliferation,induce apoptosis,and modulate oxidative stress in AGS cells.However,further in vivo and molecular studies are needed to verify its anticancer efficacy.

Ellagic Acid Enhances Antioxidant System Activity and Maintains the Quality of Strawberry Fruit during Storage

Ellagic acid(EA)is a natural antioxidant,widely present in a lot of forms’soft fruits,nuts,and other plant tissues,and helpful for promoting human health;however,its protective effect on postharvest fruit and improving the quality index of postharvest fruit have rarely been studied.In this experiment,the strawberries were soaked in 0,100,200,300,400,and 500 mg L^(−1) EA,respectively,and the influential EA on fruit quality and the antioxidant system of strawberries were studied.Compared with the control,EA treatment can reduce the browning degree and rotting rate of strawberry fruit during storage and augment the soluble solid content(SSC).EA treatment can also increase the content of related stuff and enzyme activity in antioxidant systems;the gene expression level of polyphenol oxidase(PPO)in strawberries treated with EA was always down-regulated,correspondingly,the expression of other antioxidant enzyme genes was enhanced.Among the strawberry fruits treated with EA of different concentrations,300 mg L^(−1) EA had the best effect in the process of strawberry preservation.The results suggested that the proper concentration of exogenous EA at 300 mg L−1 could maintain strawberries’quality and enhance the antioxidant system by improving the activities of antioxidative enzymes and the ascorbateglutathione(AsA-GSH)cycle during storage.

Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling

De spite cisplatin has been widely used in the treatment of various cancers,the noteworthy nephrotoxicity greatly constrained its clinical value.For this reason,finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant.Our previous study found that histone deacetylase sirtuin 6(SIRT6)could be an ideal target for the treatment of cisplatin-induced acute kidney injury.In this study,we explored the protective effects of ellagic acid,a natural polyphenol compound that activates SIRT6,on cisplatin-induced nephrotoxicity.Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells.Moreover,ellagic acid ameliorated renal dysfunction,apoptosis and fibrosis induced by cisplatin in mice.Furthermore,ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin(IL)-1βand IL-6 expression both in vitro and in vivo.Mechanistically,ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor(TNF)-αexpression.And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis,indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation.Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury,and support ellagic acid as a potential adjunctive therapy for future cancer treatment.

In vitro and in vivo antioxidant activities of three major polyphenolic compounds in pomegranate peel: Ellagic acid, punicalin, and punicalagin

Pomegranates is abundant in polyphenols and is well-known for its antioxidant activity. Punicalagin （PG） is a major poly- phenolic compound in the pomegranate peel. In certain conditions, PG can be hydrolyzed to punicallin （PL） and ellagic acid （EA）, and PL can be further hydrolyzed to EA. PG, PL, and EA all play important roles in the antioxidant activity of pomegranate peels. This study was conducted to compare the in vitro antioxidant activity and in vivo anti-oxidative stress effects of PG, PL, and EA. For the in vitro test, 2,2-diphenyl-l-picrylhydrazyl radical （DPPH.） and superoxide anion （O2~） scavenging capacities, ferric-reducing antioxidant power （FRAP）, and lipid peroxidation （LPO） inhibition capacities of PG, PL, and EA were tested. For the in vivo test, oxidatively stressed mice, which were induced by oxidized fish oil, were administrated PG, PL or EA （10 mg kg-1 d-1） for 21 days. The results showed that the in vitro antioxidant activity trends were EA〉PG〉PL〉Trolox in scavenging DPPH., PG〉PL〉EA=Trolox in scavenging O2~, EA〉PG=PL〉Trolox in FRAP, and Trolox〉PG〉EA〉PL in LPO inhibition. In the in vivo test, the EAt＇reatment increased the average daily weight gain and total antioxidant capacity （T-AOC） in the plasma （P〈0.05）, liver （P〈0.05）, and intestine （P〈0.05） in oxidatively stressed mice. It increased the superoxide dismutase （SOD） activity in the liver （P〈0.05） and intestine （P〈0.05）. It increased the glutathi- one peroxidase （GSH-Px） activity in the intestine （P〈0.05） and the intestinal villus height to crypt depth ratio （P〈0.05）. EA treatment decreased the malondialdehyde （MDA） content in the plasma （P〈0.05）, liver （P〈0.05）, and intestine （P〈0.05） and the mRNA expressions of the pro-inflammatory factors, TNF-a （P〈0.05）, IFN-y （P〈0.05） and IL-6 （P〈0.05）. PL increased the SOD （P〈0.05） and GSH-Px activities （P〈0.05） in the intestine and decreased the MDA content （P〈0.05） and the mRNA expressions of TNF-a （P〈0.05） and IL-6 （P〈0.05） in the intestine. PG increased the SOD activity （P〈0.05） and GSH-Px activity （P〈0.05） in the intestine and decreased the MDA content in the intestine （P〈0.05） and IL-6 mRNA expression in the intestine （P〈0.05）. In summary, EA, PL, and PG all had powerful in vitro antioxidant capacities, and they had different antioxidant advantages in acting against different types of radicals; EA was more effective than PL and PG in protecting against oxidative injury in vivo, especially for intestinal injury. These findings suggest that multiple polyphenol compounds in pomegranate peel may exert superior antioxidant activity than single purified polyphenols; when using pomegranate peels as health-promoting additive in animal feed, raising EA content by methods of hydrolysis or fermentation in advance could achieve better effects.

Aceclofenac-induced hepatotoxicity:An ameliorative effect of Terminalia bellirica fruit and ellagic acid

BACKGROUND Aceclofenac(ACF),a widely used nonsteroidal anti-inflammatory drug,has been associated with a number of severe cases of clinical hepatotoxicity.Terminalia bellirica,an evergreen tree,is known to have several ethnomedicinal uses including antioxidant and hepatoprotective effects.Hence T.bellirica fruit extracts and its phytoconstituent ellagic acid(EA)are expected to provide protection against oxidative stress and liver damage produced by long-term use of ACF.AIM To evaluate the antioxidant and hepatoprotective activities of T.bellirica fruit extracts and EA against ACF-induced toxicity in albino Wistar rats.METHODS The in vitro antioxidant activities of T.bellirica fruit ethyl acetate and aqueous extracts were measured by metal ion chelation and nitric oxide radical scavenging assays.The in vivo antioxidant and hepatoprotective effects of T.bellirica extracts(200 mg/kg)and EA(40 mg/kg)in ACF-induced hepatotoxic rats were assessed in serum and liver tissue after oral administration for 21 d.Silymarin(40 mg/kg)was used as a standard control.Oxidative stress markers in the blood(ferric reducing ability of plasma and lipid peroxidation inhibition)and liver tissues(superoxide dismutase,catalase and malondialdehyde)were analyzed using standard protocols.Liver function markers such as alkaline phosphatase,glutamic pyruvic transaminase,glutamic oxaloacetic transaminase,lactate dehydrogenase,γ-glutamyl transferase,creatinine,total protein,and uric acid were evaluated in rat serum.RESULTS The T.bellirica fruit ethyl acetate extract exhibited superior metal ion chelating and nitric oxide radical scavenging abilities during in vitro antioxidant assays as compared to aqueous extracts.Oral administration of ACF in rats(15 mg/kg)for 21 d produced oxidative stress and adversely affected liver function suggesting liver injury.Treatment with extracts(ethyl acetate and aqueous),EA and silymarin accounted for a significant reduction in the adverse effects of ACF on oxidative stress and liver function markers in serum and hepatic tissue in rats.Histopathological evaluation of the liver indicated that the extracts and EA significantly decreased the degree of liver damage.The in vivo efficacy of EA was higher than T.bellirica fruit extracts.Of these extracts,ethyl acetate extract revealed comparatively better antioxidant and hepatoprotective activity.CONCLUSION Ellagic acid and T.bellirica fruit extracts exhibited considerable hepatoprotective and antioxidant activities in long-term ACF-treated rats.

Dietary ellagic acid ameliorated Clostridium perfringens-induced subclinical necrotic enteritis in broilers via regulating inflammation and cecal microbiota

Background: Subclinical necrotic enteritis(SNE), a common intestinal disease of broiler caused by Clostridium perfringens, could reduce production performance of broilers by chronic intestinal damage and poor absorption of nutrients. Ellagic acid(EA) has been reported to present antioxidant and anti-inflammatory properties on human and animals in many aspects. This study was conducted to evaluate the effect and mechanism of EA in relieving SNE in broilers induced by C. perfringens.Results: C. perfringens challenge decreased body weight(BW), average daily gain(ADG), jejunal villi height/crypt depth(V/C) ratio, the activity of catalase(CAT) and the mRNA expression of zonula occludens 1(ZO-1) in jejunal mucosa of broilers. While feed conversion ratios(FCR), jejunal crypt depth(CD), the activities of myeloperoxidase(MPO) and diamine oxidase(DAO), as well as the concentrations of interleukin 6(IL-6), C-reactive protein(CRP) and procalcitonin(PCT) in serum, the activities of inducible nitric oxide synthase(iNOS) and lysozyme(LZM), the concentration of malondialdehyde(MDA), and the mRNA expressions of claudin-2, TNF-α, IL-1β, TLR-4, TLR-2, NF-κB,JAK3, STAT6 and iNOS in jejunal mucosa of broilers were increased by C. perfringens challenge. Dietary EA supplement relieved these adverse effects, and heightened jejunal villi height(VH), the concentration of D-xylose in plasma, activity of superoxide dismutase(SOD), and the mRNA expression of occludin in jejunal mucosa of broilers.The alpha diversity of cecal microbiota indicated that dietary EA supplement increased observed species and Shannon index. C. perfringens challenge increased the relative abundance of Firmicutes and decreased the relative abundance of Desulfobacterota in cecal microbiota. EA increased the relative abundance of Firmicutes in cecal microbiota. LEfSe analysis showed that C. perfringens challenge triggered the imbalance of cecal microbiota in broilers, dietary EA supplementation led to a small beneficial effect on microbiota, while the simultaneous effect of them seemed to stimulate the immune function of broilers by improving the microbiota balance.Conclusions: Dietary EA ameliorated C. perfringens-induced SNE in broilers via regulating jejunal inflammation signaling pathways TLR/NF-κB and JAK3/STAT6, relieving jejunal oxidative stress and balancing cecal microbiota to inhibit intestinal barrier damage, prevent systemic inflammatory response and improve nutrient absorption capacity,finally protect and enhance growth performance of broilers.

Comparison of the impact of epigallocatechin gallate and ellagic acid in an experimental cataract model induced by sodium selenite

AIM：To compare the potential protective effects of epigallocatechin gallate（EGCG） and ellagic acid（EA） in an experimental cataract model.●METHODS：Twenty-eight Spraque-Dawley rat pups were assigned into four groups.All the rats,except for those in the control group,were injected subcutaneously sodium selenite to induce experimental cataract on the postpartum ninth day,and between 10 th and 14 th days.Rats in the sham,EGCG,and EA groups were intraperitoneally administered 50 mg/（kg·d） saline solution,50 mg/（kg·d） EGCG and 200 mg/（kg·d） EA,respectively.The reduced glutathione（GSH） and malondialdehyde（MDA） levels,total antioxidant status（TAS） and total oxidant status（TOS） in lens supernatants were measured.RESULTS：The mean cataract gradings in EGCG and EA groups were found to be significantly lower than that in sham group（P〈0.001）.The mean GSH levels and TASs in EGCG and EA groups were significantly higher than that in sham group while mean MDA levels and TOSs in EGCG and EA groups were significantly lower than that in the sham group（P〈0.001）.CONCLUSION：EGCG and EA have protective effects on cataract development via the inhibition of oxidative stress.

Influence of chemical penetration enhancers on skin permeability of ellagic acid-loaded niosomes

This study aimed to develop niosomes of ellagic acid(EA),a potent antioxidant phytochemical substance,for dermal delivery and to investigate the influence of chemical penetration enhancers on the physicochemical properties of EA-loaded niosomes.The EA niosomes were prepared by reverse phase evaporation method using Span 60,Tween 60 and cholesterol as vesicle forming agents and Solulan C24 as a steric stabilizer.Polyethylene glycol 400(PEG)was used as a solubilizer while dimethylsulfoxide(DMSO)or Nmethyl-2-pyrrolidone(NMP)was used as a skin penetration enhancer.It was found that the mean particle sizes of EA-loaded niosomes were in the range of 312e402 nm with PI values of lower than 0.4.The niosomes were determined to be spherical multilamellar vesicles as observed by transmission electron microscope and optical microscopy.All niosomes were stable after 4 months storage at 4
C.In vitro skin permeation through human epidermis revealed that the skin enhancers affected the penetration of EA from the niosomes at 24 h.The DMSO niosomes showed the highest EA amount in epidermis;whereas the NMP niosomes had the highest EA amount in the acceptor medium.Concomitantly,the skin distribution by confocal laser scanning microscopy showed the high fluorescence intensity of the DMSO niosomes and NMP niosomes at a penetration depth of between 30e90 mm(the epidermis layer)and 90e120 mm(the dermis layer)under the skin,respectively.From the results,it can be concluded that the DMSO niosomes are suitable for epidermis delivery of EA while the NMP niosomes can be used for dermis delivery of EA.

Development and validation of a RP-HPLC method for the simultaneous determination of Embelin,Rottlerin and Ellagic acid in Vidangadi churna

Vidangadi churna is a popular Ayurvedic formulation described in the chapter Krimicikitsa of the Ayurvedic literature Cakradatta for the treatment of Krimiroga. The preparation is a composite mixture of the fine powder of fruits of Vidang （Embelia ribs）, glandular trichomes of the fruits of Kamala （Mallotus philippensis）, mature fruits of Harde （Terminalia chehula）, Saindhava and Yavakshara. The use of reversed phase C18 column eluted with gradient mobile phase of acetonitrile and water enabled the efficient separation of the chemical markers in 22 rain. Validation of the method was performed in order to demonstrate its selectivity, accuracy, precision, repeatability and recovery. All calibration curves showed good linear correlation coefficients （r2〉0.995） within the tested ranges. Three markers in Vidangadi churna were quantitied with respect to Embelin （0.647%, w/w）, Rottlerin （4.419%, w/w）, and Ellagic acid （0.459%, w/w）. lntraand inter-day RSDs of retention times and peak areas were less than 3.12%. The recoveries were between 99.66% and 102.33%. In conclusion, a method has been developed for the simultaneous quantification of three markers in Vidangadi churna. The RP-HPLC method was simple, precise and accurate and can be used for the quality control of the raw materials as well as formulations.

Effects of Season, Variety, and Processing Method on Ellagic Acid Content in Pomegranate Leaves

Ellagic acid （EA） has aroused great interest worldwide owing to its antioxidant, anti-inflammatory, and anticarcinogenetic properties. The EA content in pomegranate leaf was measured in this study using high performance liquid chromatography to investigate the effects of season, variety, and processing method on the EA level. The results show that the EA content in 11 varieties of pomegranate from the Zaozhuang region in China range from 1.30 mg · g^-1 to 6.46 mg · g^-1 of dry weight in five consecutive seasons from June to October. An analysis of variance （ANOVA） shows that the EA content is significantly dependent on the season （p〈0.05）. The EA content increases significantly during the growing season to the highest level in September and October. The effect of the leaf variety on the EA content is less significant than the season. The processing methods have different effects on the EA content. Soaking for 24 hours slightly increases the EA content （p〈0.05）. Heating at 80℃ or 100℃ for 1 h after soaking has little influence on the EA content, while slow-fired cooking at high temperature significantly elevates the EA content （p〈0.05）. To improve quality and stability, several parameters such as leaf collection time, slow-fired cooking, and cooking time should be strictly controlled during the processing of pomegranate leaf tea and its extract.

Dietary ellagic acid supplementation attenuates intestinal damage and oxidative stress by regulating gut microbiota in weanling piglets

Intestinal oxidative stress triggers gut microbiota dysbiosis,which is involved in the etiology of postweaning diarrhea and enteric infections.Ellagic acid(EA)can potentially serve as an antioxidant supplement to facilitate weaning transition by improving intestinal oxidative stress and gut microbiota dysbiosis.Therefore,we aimed to investigate the effects of dietary EA supplementation on the attenuation of intestinal damage,oxidative stress,and dysbiosis of gut microbiota in weanling piglets.A total of126 piglets were randomly assigned into 3 groups and treated with a basal diet and 2 m L saline orally(Ctrl group),or the basal diet supplemented with 0.1%EA and 2 m L saline orally(EA group),or the basal diet and 2 m L fecal microbiota suspension from the EA group orally(FEA group),respectively,for 14 d.Compared with the Ctrl group,EA group improved growth performance by increasing average daily feed intake and average daily weight gain(P<0.05)and decreasing fecal scores(P<0.05).EA group also alleviated intestinal damage by increasing the tight junction protein occludin(P<0.05),villus height,and villus height-to-crypt depth ratio(P<0.05),while decreasing intestinal epithelial apoptosis(P<0.05).Additionally,EA group enhanced the jejunum antioxidant capacity by increasing the total antioxidant capacity(P<0.01),catalase(P<0.05),and glutathione/oxidized glutathione(P<0.05),but decreased the oxidative metabolite malondialdehyde(P<0.05)compared to the Ctrl group.Compared with the Ctrl group,EA and FEA groups increased alpha diversity(P<0.05),enriched beneficial bacteria(Ruminococcaceae and Clostridium ramosum),and increased metabolites short-chain fatty acids(P<0.05).Correspondingly,FEA group gained effects comparable to those of EA group on growth performance,intestinal damage,and intestinal antioxidant capacity.In addition,the relative abundance of bacteria shifted in EA and FEA groups was significantly related to the examined indices(P<0.05).Overall,dietary EA supplementation could improve growth performance and attenuate intestinal damage and oxidative stress by regulating the gut microbiota in weanling piglets.

Ellagic acid in strawberry(Fragaria spp.):Biological,technological,stability,and human health aspects

Ellagic acid(EA)is one of the plant phenolics associated with human health benefits.It derives from ellagitannins found in some nuts,seeds,and fruits,especially berries.Strawberries are considered a functional food and nutraceutical source,mainly because of their high concentration of EA and its precursors.This review presents the current state of knowledge regarding EA,focusing on its content in strawberry plants,stability during processing and storage of strawberry-based foods,production methods,and relevance to human health.As alternatives to acid-solvent extraction,fermentation-enzymatic bioprocesses hold great promises for more eco-efficient production of EA from plant materials.Strawberry fruits are generally rich in EA,with large variations depending on cultivar,growth conditions and maturity at harvest.High EA contents are also reported in strawberry achenes and leaves,and in wild strawberries.Strawberry postharvest storage,processing and subsequent storage can influence EA content.EA low concentration in strawberry juice and wine can be increased by incorporating pre-treated achenes.Widespread recognition of strawberries as functional foods is substantiated by evidence of EA biological effects,including antioxidant,antiinflammatory,antidiabetic,cardioprotective,neuroprotective,and prebiotic effects.The health benefits attributed to EA-rich foods are thought to involve various protective mechanisms at the cellular level.Dietary EA is converted by the intestinal microbiota to urolithins,which are better absorbed than EA and may contribute significantly to the health effects attributed to EA-rich foods.Based on the evidence available,strawberry EA shows strong promises for functional,nutraceutical,and pharmaceutical applications.Future research should be directed at quantifying EA in different parts of the strawberry plant and in their byproducts;optimizing EA production from byproducts;understanding the biological actions of EA-derived metabolites in vivo,including the interactions between EA metabolites,other substances and food/biological matrices;characterizing the conditions and microorganisms involved in urolithin production;and developing delivery systems that enhance EA functionality and bioactivity.

Serum albumin complexed with ellagic acid from pomegranate peel and its metabolite urolithin B

As one of fruit waste by-products,the pomegranate peel is rich in bioactive compounds such as ellagic acid.Ellagic acid and its main gut microbial metabolite urolithin B have been reported to exhibit numerous biological activities and widely used as dietary supplements in the past decades.Interaction of these two compounds to serum albumin(SA)might affect their metabolism,efficacy,and body distribution.The interaction of ellagic acid and urolithin B with SA was investigated and BSA interference on the anti-cancer activity of these two compounds was also evaluated.Results of spectra experiments showed that ellagic acid and urolithin B could form complexes with bovine serum albumin(BSA)and urolithin B has a higher binding force and number of binding sites than ellagic acid when forming a complex with BSA.The results of molecular docking and molecular dynamics simulations suggested that ellagic acid and urolithin B tended to bind in site I rather than site II.The MTT assay results indicated that the IC_(50) value of ellagic acid decreased from 123.58μM to 55.91μM,while the IC_(50) value of urolithin B decreased from 83.67μM to 47.40μM.Ellagic acid and urolithin B can form complexes with serum albumin and the anti-cancer activity of ellagic acid and urolithin B was enhanced when combined with BSA.

Muscadine or amla extracts standardized to ellagic acid content ameliorate glucolipotoxicity associatedβ-cell dysfunction via inhibition of IL-1βand improved insulin secretion

Glucolipotocixity induces IL-1βsecretion which impairs pancreaticβ-cell insulin secretion.Ellagic acid and urolithin A have strong anti-inflammatory effect on cells.Muscadine and amla are very good sources of ellagic acid.The present study examined the effect of ellagic acid,ellagic acid-rich muscadine or amla extract,or urolothin A on inflammation inβcells under glucolipotoxic conditions.Rat NIT-1βcells were incubated in glucolipotoxic conditions(33.3 mM glucose,250μM palmitic acid or 33.3 mM glucose+250μM palmitic acid with or without ellagic acid,ellagic acid-rich muscadine or amla extracts standardized to its ellagic acid content,or urolithin A).Inflammatory status was evidenced by ELISA analysis of insulin and IL-1βsecretion.Ellagic acid-rich muscadine or amla extracts dose-dependently stimulated insulin secretion and down-regulated IL-1βbetter than pure ellagic acid,or urolithin A.Urolithin A did not statistically stimulate insulin secretion and did not inhibit IL-1β.

Pomegranate peel extract lessens histopathologic changes and restores antioxidant homeostasis in the hippocampus of rats with aluminium chloride-induced Alzheimer’s disease

Objective:To investigate the neuroprotective efficacy of pomegranate and ellagic acid on the histopathological changes in the hippocampus of an aluminium chloride(AlCl<sub>3)induced rat model of Alzheimer’s disease.Methods:Sprague Dawley rats were divided into 4 groups(n=10each):GroupⅠ:serving as negative control;GroupⅡ,Alzheimer model,induced by administration of 17 mg/kg bw AlCl3;GroupⅢ,administered the same dose of AlCl3 with 50 mg/kg of pomegranate peel extract and GroupⅣ:administered ellagic acid(50 mg/kg)in addition to the same dose of AlCl3.The medication given to all groups continued for 28 days.All were given the compounds by gastric gavage.Radial arm maze test,hippocampus antioxidant markers,histopathology of the dentate gyrus,and CA3 of the hippocampus were evaluated.Results:Rats treated with pomegranate peel extract exposed to radial arm maze test showed less number of errors and reduced time needed to reach the criterion.There was an increase in the levels of glutathione,catalase,and total antioxidant capacity and decreased lipid peroxidation products.Histopathological features in dentate gyrus and CA3 as apoptosis and chromatolysis of pyramidal cells and granular layer,respectively,were decreased.Alzheimer characteristic neurofibrillary tangles and senile plaques were reduced.Treatment with ellagic acid ameliorated the pathological results but to a statistically lower level.Conclusions:Pomegranate peel extract alleviates memory deficit and restores antioxidant homeostasis following degenerative changes in the hippocampus induced by aluminium chloride in rats.

A New Polyphenolic Compound from Rubus aleaefolius and Its Inhibitory Activity on Mammalian Cell Cycle at G_0/G_1 Phase

Rubuphenol (1), a new polyphenolic compound, was isolated together with the known ellagic acid (2) as new cell cycle inhibitors from Rubus aleaefolius Poir. through a bioassay-guided separation procedure and the structure of 1 was elucidated by spectroscopic method. Compounds 1 and 2 inhibited the cell cycle of tsFT210 cells at the G0/G1 phase respectively with the MIC values of 14.6 mM and 10.3 mM.

Overexpressed SIRT6 ameliorates doxorubicin-induced cardiotoxicity and potentiates the therapeutic efficacy through metabolic remodeling

Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore,overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment.Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicininduced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice.These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.

Punica granatum果实皮甲醇提取物化学成分的分离和标准化(英文)

AIM:The present study was undertaken to isolate and standardize the various active phytochemical constituents present in the fruit rinds of Punica granatum.METHODS:Fruit rinds of Punica granatum were dried and extracted with methanol in a static extractor;the percentage yield of the methanolic extract (MEPG) was found to be 26%;the methanolic extract was partitioned using n-butanol,ethyl acetate and water;the percentage yield of the fractions were found to be 17.16%,26.88% and 47.72% respectively.HPLC was carried out for all the fractions and the markers corresponding to the major peaks in HPLC were isolated using column chromatography.The isolated markers were characterized using UV,IR,Mass and NMR spectroscopy.RESULTS & CONCLUSION:Totally four compounds were isolated and identified as punicalin,punicalagin,gallic acid and ellagic acid based on UV,IR,Mass and NMR data,they were standardized by HPLC.

Effect of raspberry extract on wound healing

The main purpose of this study was to investigate the effect of raspberry extract on wound healing and compare it with that of ellagic acid.The elimination of excess free radicals was the key to preventing wound inflammation;cellular antioxidation activity was evaluated using an oxidative stress damage cell model.Cell proliferation ability was measured using the WST1 assay,and the migration capacity was determined using the wound scratch assay.A mouse wound model was used to verify the effect of raspberry extract on wound healing.The cellular antioxidant activity of the extract((50.31±3.17)pg/mL)was slightly lower than that of ellagic acid((44.59±2.38)pg/mL).The results of a cell proliferation assay showed that both raspberry extract and ellagic acid at 5μg/mL could significantly(P<0.01)promote the proliferation of HaCaT cells.After culturing for 24 h and 48 h,the cell healing rates of the extract were(41.11±0.38)per cent and(68.88±2.51)per cent,respectively,whereas the corresponding rates of ellagic acid were(39.01±2.40)per cent and(70.33±0.89)per cent;hence,there were no significant differences between them(P>0.05).The wound areas of mice fed low,medium,and high doses of raspberry extract for 14 days were 1.66,1.41,and 1.24 mm2,respectively,which were sign讦icantly lower than that of the blank control group,2.18 mm2(F<0.05).These findings indicate that raspberry extract and ellagic acid exhibit similar antioxidant capacities and equivalent cell proliferation-promoting capabilities.In the mouse test,raspberry extract effectively promoted a reduction in wound area.This work demonstrates the potential of raspberry extract in wound healing,suggesting a promising application of raspberry resources in the fields of functional foods,cosmetics,and medicine.