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Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24‐month‐old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for 4 weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total ‐SH groups and malonaldehyde; MDA), liver enzymes in serum and in silico analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate–cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old‐aged liver. [ABSTRACT FROM AUTHOR]

Eriocitrin is a flavonoid glycoside with strong antioxidant capacity that has a variety of pharmacological activities, such as hypolipidemic, anticancer and anti-inflammatory effects. We found that the gut microbiota could rapidly metabolize eriocitrin. By using LC/MSn-IT-TOF, we identified three metabolites of eriocitrin metabolized in the intestinal microbiota: eriodictyol-7-O-glucoside, eriodictyol, and dihydrocaffeic acid. By comparing these two metabolic pathways of eriocitrin (the gut microbiota and liver microsomes), the intestinal microbiota may be the primary metabolic site of eriocitrin metabolism. These findings provide a theoretical foundation for the study of pharmacologically active substances. [ABSTRACT FROM AUTHOR]

Eriocitrin, a flavanone found in peppermint and citrus fruits, is known to possess many physiological activities. However, the anti-angiogenic effects of eriocitrin are yet to be fully elucidated. Therefore, the objective of this research was to explore the anti-angiogenic effects of eriocitrin both in vitro and in vivo as well as its underlying mechanism. Anti-angiogenic effects of eriocitrin were evaluated utilizing in vitro models of angiogenesis, including inhibition of tube formation, and induction of apoptosis in human umbilical vein endothelial cells (HUVECs). A chorioallantoic membrane (CAM) assay in chick embryos was also performed to evaluate the in vivo effects of eriocitrin on angiogenesis. Results showed significant eriocitrin effects on proliferation, tube formation, migration, and apoptosis in HUVECs. Furthermore, in vivo analysis revealed that eriocitrin significantly suppressed the formation of new blood vessels. In particular, it regulated MAPK/ERK signaling pathway and VEGFR2, inhibited the downstream PI3K/AKT/mTOR signaling pathway, and activated apoptosis signals such as caspase cascades. In HUVECs, the expression of matrix metalloproteinases (MMP-2 and MMP-9) exhibited an inhibitory effect on angiogenesis through the suppression of the signaling pathway. Therefore, eriocitrin presents potential for development into an antiangiogenic therapeutic agent. [ABSTRACT FROM AUTHOR]

Background: Hemolysis and eryptosis result in the premature elimination of circulating erythrocytes and thus contribute to chemotherapy-related anemia, which is extremely prevalent in cancer patients. Eriocitrin (ERN), a flavanone glycoside in citrus fruits, has shown great promise as an anticancer agent, but the potential toxicity of ERN to human erythrocytes remains unstudied. Methods: Erythrocytes were exposed to anticancer concentrations of ERN (10–100 μM) for 24 h at 37 °C, and hemolysis and associated markers were quantified using colorimetric assays. Eryptosis was assessed by flow cytometric analysis to detect phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca2+ using Fluo4/AM, and oxidative stress with 2-,7-dichlorodihydrofluorescin diacetate (H2DCFDA). ERN was also tested against specific signaling inhibitors and anti-hemolytic agents. Results: ERN caused significant, concentration-dependent hemolysis at 20–100 μM. ERN also significantly increased the percentage of eryptotic cells characterized by Ca2+ elevation and oxidative stress. Furthermore, the hemolytic activity of ERN was significantly ameliorated in the presence of D4476, NSC23766, isosmotic urea and sucrose, and polyethylene glycol 8000 (PEG). In whole blood, ERN significantly elevated MCV and ESR, with no appreciable effects on other peripheral blood cells. Conclusions: ERN promotes premature erythrocyte death through hemolysis and eryptosis characterized by PS externalization, Ca2+ accumulation, membrane blebbing, loss of cellular volume, and oxidative stress. These toxic effects, mediated through casein kinase 1α and Rac1 GTPase, can be ameliorated by urea, sucrose, and PEG. Altogether, these novel findings are relevant to the further development of ERN as an anticancer therapeutic. [ABSTRACT FROM AUTHOR]

Eriocitrin, a flavanone found in peppermint and citrus fruits, is known to possess many physiological activities. However, the anti-angiogenic effects of eriocitrin are yet to be fully elucidated. Therefore, the objective of this research was to explore the anti-angiogenic effects of eriocitrin both in vitro and in vivo as well as its underlying mechanism. Anti-angiogenic effects of eriocitrin were evaluated utilizing in vitro models of angiogenesis, including inhibition of tube formation, and induction of apoptosis in human umbilical vein endothelial cells (HUVECs). A chorioallantoic membrane (CAM) assay in chick embryos was also performed to evaluate the in vivo effects of eriocitrin on angiogenesis. Results showed significant eriocitrin effects on proliferation, tube formation, migration, and apoptosis in HUVECs. Furthermore, in vivo analysis revealed that eriocitrin significantly suppressed the formation of new blood vessels. In particular, it regulated MAPK/ERK signaling pathway and VEGFR2, inhibited the downstream PI3K/AKT/mTOR signaling pathway, and activated apoptosis signals such as caspase cascades. In HUVECs, the expression of matrix metalloproteinases (MMP-2 and MMP-9) exhibited an inhibitory effect on angiogenesis through the suppression of the signaling pathway. Therefore, eriocitrin presents potential for development into an antiangiogenic therapeutic agent.

Summary: In this study, the extraction of bioactive compounds from lemon peel, a by‐product of the food industry, was investigated using pressurised hot water extraction (PHWE) at different extraction temperatures (40–200 °C) and times (5–30 min) under 10.34 MPa pressure. The selectivity of the PHWE process on eriocitrin and hesperidin extraction was also tested. The highest total phenolic content (TPC) (59.57 mg gallic acid equivalents g−1), total flavonoid content (TFC) (8.22 mg catechin equivalents g−1) and antioxidant capacity by DPPH (42.59 mg Trolox equivalents (TE) g−1) were obtained at 160 °C for 30 min. The maximum eriocitrin (30.41 mg g−1) and hesperidin (25.90 mg g−1) contents were achieved at 160 °C for 5 min with a 5‐hydroxymethyl furfural content of 0.07 mg g−1. PHWE provided better results for individual compounds and antioxidant capacities than conventional extraction. The results indicated the potentiality of PHWE in the selective extraction of eriocitrin and hesperidin from lemon peel by controlling the extraction temperature and time. [ABSTRACT FROM AUTHOR]

The most significant reactive α-dicarbonyl RCS involved in the pathomechanism of glycation and related diseases is methylglyoxal (MGO). Hyperglycemia promotes the generation of MGO and leads to the formation of advanced glycation end products (AGEs). Therefore, MGO trapping and glycation inhibition appear to be important therapeutic targets in prediabetes, diabetes, and in the early prevention of hyperglycemic complications. Peppermint leaf is commonly used as herbal tea, rich in polyphenols. Eriocitrin, its predominant component, in a double-blind, randomized controlled study reversed the prediabetic condition in patients. However, the antiglycation activity of this plant material and its polyphenols has not been characterized to date. Therefore, the aim of this study was to evaluate the ability of a peppermint leaf dry extract and its polyphenols to inhibit non-enzymatic protein glycation in a model with bovine serum albumin (BSA) and MGO as a glycation agent. Peppermint polyphenols were also evaluated for their potential to trap MGO in vitro, and the resulting adducts were analyzed by UHPLC-ESI-MS. To relate chemical composition to glycation inhibitory activity, the obtained peppermint extract was subjected to qualitative and quantitative analysis. The capability of peppermint leaf polyphenols to inhibit glycation (27.3–77.2%) and form adducts with MGO was confirmed. In the case of flavone aglycones, mono- and di-adducts with MGO were observed, while eriodictyol and eriocitrin effectively produced only mono-adducts. Rosmarinic acid and luteolin-7-O-glycosides did not reveal this action. IC50 of the peppermint leaf dry extract was calculated at 2 mg/mL, equivalent to a concentration of 1.8 μM/mL of polyphenols, including ~1.4 μM/mL of flavonoids and ~0.4 μM/mL of phenolic acids. The contribution of the four major components to the anti-AGE activity of the extract was estimated at 86%, including eriocitrin 35.4%, rosmarinic acid 25.6%, luteolin-7-O-rutinoside 16.9%, luteolin-7-O-β-glucuronoside 8.1%, and others 14%. The effect of peppermint dry extract and polyphenols in inhibiting MGO-induced glycation in vitro was comparable to that of metformin used as a positive control. [ABSTRACT FROM AUTHOR]

Background: Hemolysis and eryptosis result in the premature elimination of circulating erythrocytes and thus contribute to chemotherapy-related anemia, which is extremely prevalent in cancer patients. Eriocitrin (ERN), a flavanone glycoside in citrus fruits, has shown great promise as an anticancer agent, but the potential toxicity of ERN to human erythrocytes remains unstudied. Methods: Erythrocytes were exposed to anticancer concentrations of ERN (10–100 μM) for 24 h at 37 °C, and hemolysis and associated markers were quantified using colorimetric assays. Eryptosis was assessed by flow cytometric analysis to detect phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca2+ using Fluo4/AM, and oxidative stress with 2-,7-dichlorodihydrofluorescin diacetate (H2DCFDA). ERN was also tested against specific signaling inhibitors and anti-hemolytic agents. Results: ERN caused significant, concentration-dependent hemolysis at 20–100 μM. ERN also significantly increased the percentage of eryptotic cells characterized by Ca2+ elevation and oxidative stress. Furthermore, the hemolytic activity of ERN was significantly ameliorated in the presence of D4476, NSC23766, isosmotic urea and sucrose, and polyethylene glycol 8000 (PEG). In whole blood, ERN significantly elevated MCV and ESR, with no appreciable effects on other peripheral blood cells. Conclusions: ERN promotes premature erythrocyte death through hemolysis and eryptosis characterized by PS externalization, Ca2+ accumulation, membrane blebbing, loss of cellular volume, and oxidative stress. These toxic effects, mediated through casein kinase 1α and Rac1 GTPase, can be ameliorated by urea, sucrose, and PEG. Altogether, these novel findings are relevant to the further development of ERN as an anticancer therapeutic.

Introduction: Eriocitrin, found in lemon fruit, has shown a wide range of biological properties. Herein, we investigated the intestinal metabolic profile of eriocitrin in colon, and the regulation of dietary intervention of eriocitrin on gut microbiota. Methods: We performed ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS), 16S rDNA gene sequencing and gas chromatography-mass (GC-MS) on colon contents from the eriocitrin group (n=6), and compared them with control participants (n=6). Results: A total of 136 flavonoids were found in colon contents, including eriocitrin and its six metabolites (eriodictyol, homoeriodictyol, hesperetin, eriodictyol-3'-O-glucoside, hesperetin-7-O-glucoside and eriodictyol-7-O-(6"-O-galloyl) glucoside). Moreover, dietary intervention of eriocitrin significantly alters the beta diversity of the gut microbiota, the probiotics such as Lachnospiraceae_UCG_006 were significantly enriched, and the production of butyrate, valerate and hexanoate in the colon pool of short-chain fatty acids were significant increased. The spearman's association analysis performed some intestinal bacteria may be involved in the metabolism of eriocitrin. Discussion: Collectively, our results preliminarily suggest the metabolism of eriocitrin in the gut, demonstrating alterations of eriocitrin in gut microbiota, which warrants further investigation to determine its potential use in food and biomedical applications. [ABSTRACT FROM AUTHOR]

This double-blind, randomized, placebo/controlled, crossover study evaluated the efficacy of Eriomin® in reducing hyperglycemia and improving diabetes-related biomarkers in individuals with hyperglycemia above 110 mg/dL (mean 123 ± 18 mg/dL). Subjects (n = 30), divided into two groups (Eriomin or Placebo), who received a dose of 200 mg/d of the designated supplement for 12 weeks and, after a washout period of 2 weeks, switched to the other supplement in the following 12 weeks. Assessments of biochemical, metabolic, inflammatory, blood pressure, anthropometry, and dietary parameters were performed at the beginning and end of each intervention. Treatment with 200 mg/d of Eriomin significantly decreased blood glucose (−5%), homeostasis model assessment of insulin resistance (−11%), glucagon (−13%), interleukin-6 (−14%), tumor necrosis factor alpha (−20%), and alkaline phosphatase (−13%); but increased glucagon-like peptide 1 (GLP-1) by (17%) (P ≤ .05). At the end of the placebo period, there was a 13% increase in triglycerides (P ≤ .05). Other parameters evaluated did not change with Eriomin or placebo. In conclusion, intervention with Eriomin benefited the glycemic control of prediabetic and diabetic patients, with higher blood glucose levels, by increasing GLP-1 and decreasing systemic inflammation. [ABSTRACT FROM AUTHOR]

The present study aimed to recognize the recent literature to highlight the pharmacological impacts and highlight the therapeutic potential of the active molecule eriocitrin. Citrus limon are a good resource of the flavanone eriocitrin (eriodictyol 7-O-β-D-rutinoside). Eriocitrin has potent biological actions due to its strong antioxidant, antitumor, anti-allergic, antidiabetic and anti-inflammatory activities. Eriocitrin is more potent in suppressing oxidative stress in diabetes mellitus (DM) and other chronic diseases incurred by excessive oxidative stress. During metabolism, eriocitrin is metabolized by gut microbiota, and a chain of molecules such as eriodictyol, methy-eriodictyol, 3,4-dihydroxyhydrocinnamic acid (DHCA), and much more conjugated molecules. More in-depth studies are recommended to explore this drug for clinical trials.

Background: Inflammation is a natural reaction that the body has when exposed to physical damage. Inflammation in numerous organs implies atherosclerosis, diabetes, dermatitis, arthritis, obesity, and cancer. The review's objective was to summarize the currently known eriocitrin's anti-inflammatory effects. Methods: A review was conducted on a study of the anti-inflammatory effects of eriocitrin conducted from January 2010 to April 2021. Results: Based on eligibility criteria, six studies were included in this study consisting of in vitro and in vivo studies. Some pharmacological studies have suggested that eriocitrin has the potential to treat diseases involving inflammatory responses. Nitric Oxide (NO), IL-1β, IL-6, IL-8, TNF-α, NF-κB, MPO, MAPK, and MMP-9 secretion were reduced by eriocitrin, inhibiting cell apoptosis, and the production of pro-inflammatory cytokines, but increases the content of IL-10, Nrf2, DUSP14, HO-1, and NQ01. Conclusions: Eriocitrin has been shown to have anti-inflammatory effects in both in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a hazardous heavy metal that adversely affects the vital body organs particularly liver. Eriocitrin (ERCN) is a plant-based flavonoid that is well-known for its wide range of pharmacological potential. This research trial was aimed to determine the ameliorative potential of ERCN against Cd provoked hepatotoxicity in rats. Twenty-four rats (Rattus norvegicus) were apportioned into control, Cd treated (5 mg/kg), Cd (5 mg/kg) + ERCN (25 mg/kg) and only ERCN (25 mg/kg) administrated group. Expressions of Nrf2/Keap1 pathway and apoptotic markers were assessed through qRT-PCR. The levels of inflammatory and liver function markers were evaluated by using standard ELISA kits. Cd exposure reduced the expression of Nrf2 and anti-oxidant genes as well as the activity of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione (GSH) contents while escalating the expression of Keap1. Furthermore, Cd intoxication augmented malondialdehyde (MDA) and reactive oxygen species (ROS) levels in hepatic tissues. Exposure to Cd resulted in a notable elevation in the levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST). Cd administration upregulated nuclear factor-kappa B (NF-κB), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels as well as cyclooxygenase-2 (COX-2) activity. Furthermore, Cd administration upsurged Bax and Caspase-3 expression while reducing the expression of Bcl-2. Moreover, Cd intoxication disrupted the normal architecture of hepatic tissues. However, supplementation of ERCN significantly (p < 0.05) ameliorated the aforementioned disruptions induced by Cd intoxication. ERCN treatment remarkably ameliorated the hepatic tissues owing to its antioxidant, anti-inflammatory, and anti-apoptotic potentials. These findings underscore the therapeutic potential of ERCN to counteract the adverse effects of environmental pollutants on hepatic tissues. • Cadmium dysregulated Nrf2/keap1 pathway and activities of antioxidant enzymes. • Cadmium escalated levels of oxidative stress hepatic function markers. • Cadmium increased the levels inflammatory markers. • Cadmium instigated various hepatic histological alterations. • Eriocitrin protected hepatic tissues via regulating abovementioned damages. [ABSTRACT FROM AUTHOR]

The most significant reactive α-dicarbonyl RCS involved in the pathomechanism of glycation and related diseases is methylglyoxal (MGO). Hyperglycemia promotes the generation of MGO and leads to the formation of advanced glycation end products (AGEs). Therefore, MGO trapping and glycation inhibition appear to be important therapeutic targets in prediabetes, diabetes, and in the early prevention of hyperglycemic complications. Peppermint leaf is commonly used as herbal tea, rich in polyphenols. Eriocitrin, its predominant component, in a double-blind, randomized controlled study reversed the prediabetic condition in patients. However, the antiglycation activity of this plant material and its polyphenols has not been characterized to date. Therefore, the aim of this study was to evaluate the ability of a peppermint leaf dry extract and its polyphenols to inhibit non-enzymatic protein glycation in a model with bovine serum albumin (BSA) and MGO as a glycation agent. Peppermint polyphenols were also evaluated for their potential to trap MGO in vitro, and the resulting adducts were analyzed by UHPLC-ESI-MS. To relate chemical composition to glycation inhibitory activity, the obtained peppermint extract was subjected to qualitative and quantitative analysis. The capability of peppermint leaf polyphenols to inhibit glycation (27.3–77.2%) and form adducts with MGO was confirmed. In the case of flavone aglycones, mono- and di-adducts with MGO were observed, while eriodictyol and eriocitrin effectively produced only mono-adducts. Rosmarinic acid and luteolin-7-O-glycosides did not reveal this action. IC50 of the peppermint leaf dry extract was calculated at 2 mg/mL, equivalent to a concentration of 1.8 μM/mL of polyphenols, including ~1.4 μM/mL of flavonoids and ~0.4 μM/mL of phenolic acids. The contribution of the four major components to the anti-AGE activity of the extract was estimated at 86%, including eriocitrin 35.4%, rosmarinic acid 25.6%, luteolin-7-O-rutinoside 16.9%, luteolin-7-O-β-glucuronoside 8.1%, and others 14%. The effect of peppermint dry extract and polyphenols in inhibiting MGO-induced glycation in vitro was comparable to that of metformin used as a positive control.

Purpose: To investigate the effect of eriocitrin on sevoflurane-induced neurotoxicity in mice. Methods: Mouse hippocampal neurons (HT22) were exposed to different concentrations of sevoflurane for 6 h and then incubated with different concentrations of eriocitrin for another 24 h. Cell viability was determined by CCK8 assay, while fluorescence intensity of dichlorodihydrofluorescein was used to evaluate reactive oxygen species. Enzyme linked immunosorbent assay (ELISA) was used to determine oxidative stress, and cellular apoptosis was determined by flow cytometry. Results: Sevoflurane exposure decreased HT22 cell viability, whereas incubation with eriocitrin increased viability of sevoflurane-treated HT22 cells (p < 0.05). Sevoflurane-induced increase in dichlorodihydrofluorescein fluorescence intensity was reduced by eriocitrin, but eriocitrin attenuated sevoflurane-induced increase in malondialdehyde, superoxide dismutase, and glutathione peroxidase in HT22 cells. Cell apoptosis increased after sevoflurane exposure, and eriocitrin suppressed apoptosis in sevoflurane-treated HT22 cells through downregulation of cleaved caspase-3 and cleaved caspase-9 (p < 0.05). Eriocitrin incubation enhanced protein expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in sevoflurane-treated HT22 cells (p < 0.05). Conclusion: Eriocitrin ameliorates sevoflurane-induced oxidative stress and inflammatory response in HT22 cells via activation of Nrf2/HO-1/NQO1 signaling. Thus, agent may be useful in the treatment of sevoflurane-induced toxicity, but in vivo studies are required to buttress this. [ABSTRACT FROM AUTHOR]

Eriocitrin, a lemons flavanone, exhibits several biological properties, antiproliferative, and proapoptotic effects. However, its molecular mechanical action is not entirely clarified. Oxidative stress causes abnormal stimulation of signal transducer and activator of transcription 3 (STAT3) and c‐Jun NH2‐terminal kinase (JNK), p38 mitogen‐activated protein kinases (MAPKs) signaling has been strongly connected with the ruling of cell survival and apoptosis of cancer cells. Herein, we investigated an antiproliferative and proapoptotic effect that Eriocitrin modulates STAT3/MAPKs signaling activation in MCF‐7 cells. We noticed that Eriocitrin strongly enhances reactive oxygen species (ROS) generation, alteration of mitochondrial outer membrane potential, and enhances apoptotic morphological changes. Furthermore, Eriocitrin suppressed STAT3 phosphorylation via inhibiting an upstream molecule of JAK2 and Src kinase activation, thereby blocking STAT3 nuclear translocation. Similarly, Eriocitrin causes oxidative stress‐mediated JNK/p38 MAPK signaling activation. We confirmed that Eriocitrin induced ROS‐mediated apoptosis inhibited by the antioxidant substance of N‐acetylcysteine. Eriocitrin induced apoptosis via suppression of STAT3 signaling regulated proteins, activating proapoptotic factors Bax, caspase 7, 8, 9 and suppressing Bcl‐2, Bcl‐x expression in MCF‐7 cells. Overall, these results evidenced that Eriocitrin can affect multiple signaling events associated with tumorigenesis. From this evidence, Eriocitrin, a novel chemotherapeutic agent, can be used to treat breast cancer. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of an aqueous extract of Citrus limon (L.) Osbeck (lemon extract) when used as a sensory additive in feed for all animal species. The FEEDAP Panel concluded that the additive under assessment is safe for all animal species up to the maximum proposed use levels of 1,000 mg/kg complete feed and 250 mg/kg water for drinking. No concerns for consumers were identified following the use of lemon extract up to the highest safe level in feed. The additive should be considered a skin and eye irritant, and a potential corrosive. The use of the extract in animal feed under the proposed conditions was not expected to pose a risk for the environment. Lemon extract was recognised to flavour food. Since its function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary. [ABSTRACT FROM AUTHOR]

Distillation by-products of peppermint have not been considered for the valorization of bioactive compounds. In this study, by-products of peppermint after hydrodistillation, hydrosol and distilled leaves, were investigated followed by the most effective fraction was incorporated into ice cream formulations in order to improve the health promoting effects including antioxidant and α-glucosidase inhibition capacities of the ice creams. Distilled leaves of peppermint were subjected to sequential extraction by ethyl acetate and ethanol. HPLC analyses of eriocitrin and total phenolic analysis indicated that hydrosol contained significant amount of phenolics after 2 h hydrodistillation. Extending hydrodistillation from 1 to 2 h had insignificant effects on phenolic content. Distilled leaves of peppermint had extract yield of 7.39 and 7.19 g/100 mL in 1 and 2 h ethyl acetate extraction, respectively. The predominant phenolic of peppermint (eriocitrin) was 917.5 mg/L in hydrosol after 1 h distillation. Four h distillation of peppermint resulted in decrease in the amount of eriocitrin, however, hydrosol contained valuable amount of phenolics (840.1 mg/L). Hydrosols displayed higher antioxidant capacity in all tested methods than distilled leaves. Hydrosols, at equal amount of phenolics, had higher α-glucosidase inhibition capacity (5.92 µg/mL) than ethyl acetate extract (14.62 µg/mL) and ethanol extract (17.04 µg/mL) of deodorized leaves. Hydrosols were spray dried with the aid of maltodextrin in order to increase drying yield and incorporate the spray dried hydrosol (SDH) into ice cream formulations. Among others, ice cream incorporated with 0.5% of SDH was accepted by the panelists without damaging sensorial properties of ice cream. [ABSTRACT FROM AUTHOR]

Abstract Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of an aqueous extract of Citrus limon (L.) Osbeck (lemon extract) when used as a sensory additive in feed for all animal species. The FEEDAP Panel concluded that the additive under assessment is safe for all animal species up to the maximum proposed use levels of 1,000 mg/kg complete feed and 250 mg/kg water for drinking. No concerns for consumers were identified following the use of lemon extract up to the highest safe level in feed. The additive should be considered a skin and eye irritant, and a potential corrosive. The use of the extract in animal feed under the proposed conditions was not expected to pose a risk for the environment. Lemon extract was recognised to flavour food. Since its function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary.

Tendinopathy is a common disease in elite and recreational athletes, and Eriocitrin is a flavonoid compound, which has antioxidant properties. The present study was undertaken to investigate the effect of Eriocitrin on tendon stem cells in vitro. Different concentrations of Eriocitrin (0, 25, 50, 75 µM) were used to treat tendon stem cells, cell proliferation was determined by CCK8 assay, apoptosis was detected by propidium iodide (PI) staining assays and caspase-3 activity assessment, wound-healing assaywas selected to detect the migration, and RT-PCR was chosen to detect the expression levels of scar formation-related gene markers (COMP, Fibronectin, and Biglycan). Eriocitrin treatment promoted cell proliferation of tendon stem cells in dose-dependent manner, and it reduced the apoptotic activities and improved the migration of tendon stem cells. It inhibited COMP, Biglycan, and Fibronectin expression. In summary, eriocitrin promoted cell proliferation of tendon stem cells, improved the migration of tendon stem cells, and inhibited the expression levels of some scar formation-related gene markers. [ABSTRACT FROM AUTHOR]

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Eriocitrin is a flavonoid that is isolated from orange peel. Resveratrol is a polyphenol compound, which is present in various fruits, such as grapes. The aim of the present study was to investigate both in vitro and in vivo anti-inflammatory effects of eriocitrin combined with resveratrol using lipopolysaccharide (LPS)-induced RAW264.7 cells and a mouse model of ear edema. The results showed that eriocitrin combined with resveratrol strongly inhibited LPS-induced secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and Interleukin-1β (IL-1β). Moreover, Eriocitrin combined with resveratrol potently inhibited nuclear factor-κB (NF-κB), phosphor-STAT3, and phosphor-AKT, which was accompanied by inhibition of phosphorylation in mitogen-activated protein kinase (MAPK) signaling pathways. Treatment with eriocitrin combined with resveratrol alleviated edema and subcutaneous tissue inflammation caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) in vivo. This study also demonstrated that treatment with eriocitrin and resveratrol decreased the levels of the pro-inflammatory cytokines TNF-α and IL-1β. The results of the present study indicate that eriocitrin combined with resveratrol effectively inhibits inflammatory responses both in vitro and in vivo.

Background: Stroke is ranked on top of the persistent ailments associated with the brain. The incidence of ischemic stroke is rapidly rising along with intensified mortality as well as permanent disability conditions. However, tissue plasminogen activator (tissue-type plasminogen activator) is the only FDA-approved treatment for the treatment of stroke with decreased success rate. Eriocitrin, a flavonoid compound of Citrus limon with incredible therapeutic values, was active in the current investigation to explore the neuroprotective capability in arterial occlusion-provoked cerebral ischemic reperfusion injury (CIRI) in mouse replica. Materials and Methods: The neurological defects were considered through the standard scoring method and the expression status of apoptotic proteins, i.e., nuclear factor kappa B (NF-ƙB), caspase-3, and caspase-9, was examined via western blotting test. The expression of neuronal nitric oxide synthase (nNOS) was scrutinized through real-time polymerase chain reaction and standard ELISA kits were employed to examine the status of the proinflammatory markers. Results: The arterial occlusion provoked cerebral ischemic animals displayed the severely elevated status of inflammatory markers namely interleukin-6 (IL-6), IL-1β and tumor necrosis factor α, and the expression statuses of apoptotic proteins, as well as nNOS, were also uplifted while comparing to the sham subjected animals. Amazingly, eriocitrin (100 mg/kg) treatment revealed the declined inflammatory markers level, besides, the expression patterns of apoptotic proteins and nNOS were also reduced noticeably in the cerebral ischemic-reperfusion-operated animals. Conclusion: The novel findings of this investigation were demonstrated that the Eriocitrin delivered an astounding neuroprotection in the arterial occlusion-mediated CIRI in mouse replica, which possibly a promising neuroprotectant in cerebral ischemia. [ABSTRACT FROM AUTHOR]

Eriocitrin is a citrus flavonoid with a high capacity to reduce the oxidative stress related to metabolic disorders and obesity. We assessed the effects of low doses of eriocitrin on the oxidative stress, inflammation, and metabolism of glucose and lipids of high-fat diet (HFD)-fed obese mice. Fifty male C57BL/6J mice were randomly assigned into five groups (n 10). The mice were fed an HFD (45 % kcal from fat, i.e. lard) for 4 weeks for obesity induction. After this period, the mice continued receiving the same HFD, but supplemented with eriocitrin at 10, 25 or 100 mg/kg body weight (bw) for an additional 4 weeks. Control groups were fed with standard diet (10 % kcal of fat, i.e. soy oil) or with HFD without eriocitrin, for eight consecutive weeks. At the end of the study, mice supplemented with eriocitrin showed lower levels of blood serum glucose and blood and liver triacylglycerols (P < 0⋅05). There was also improved levels of insulin, HOMA-IR, total-cholesterol, resistin and lipid peroxidation in the supplemented mice. It was concluded that the 25 mg dose of eriocitrin improved all the parameters studied and had positive effects on oxidative stress, systemic inflammation and metabolism of lipids and glucose in general.

Background: Cisplatin, a common anti-neoplastic drug used in the medical industry for cancer treatment has shown adverse nephrotoxic effects. This research targets to demonstrate the protective measure of eriocitrin, a bioactive flavonoid, against cisptin-induced renal toxicity in rats. Materials and methods: Rats of normal control and model groups were treated with saline whereas experimental groups received oral administration of eriocitrin (25 and 50 mg/kg b.w.) for 10 days and a single intraperitoneal (i.p.) injection of cisplatin (8 mg/kg b.w.) was given on the 7th day for all except normal control group. Blood serum, urine, and kidney tissue samples were collected for analysis. Results: Cisptin-induced rats demonstrated significant renal toxicity and damage. Eriocitrin dose-dependently reversed the effects by decreasing the proteinuria in urine, and urea, creatinine, lipid peroxidation, nitric oxide (NO) and pro-inflammatory cytokine levels (TNF-a, IL-1ß) in serum. The tissue levels of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were increased, whereas the levels of tissue DNA fragmentation and serum PARP-1 and Caspase-3 were reduced against model group. Histopathological modulations were supporting the protective effect of eriocitrin. Conclusion: Eriocitrin has significant nephroprotective effects against cisptin-induced renal toxicity by alleviating oxidative stress, preventing apoptosis and DNA damage. [ABSTRACT FROM AUTHOR]

• Eriocitrin and eriodictyol could quench α-glucosidase intrinsic fluorescence. • Eriocitrin and eriodictyol induce α-glucosidase conformation changes. • The binding processes were mainly driven by hydrophobic interaction. • The inhibitory effect of eriocitrin was stronger than that of eriodictyol. The inhibition of α-glucosidase activity is a prospective approach to prevent postprandial hyperglycemia. As two flavonoids extracted from citrus fruits, eriocitrin and eriodictyol have similar structures and show multiple pharmacological activities. In order to investigate the effects of flavonoids structure on enzyme inhibition, spectroscopy and molecular docking analysis were used. Saccharomyces cerevisiae α-glucosidase (GH13) was used for studying the inhibitory mechanism by multi-spectroscopic analysis. Results indicated that they could quench the intrinsic fluorescence of α-glucosidase, the binding constants at 298 K were (7.02 ± 0.22) × 104 and (4.57 ± 0.16) × 104 L mol−1, respectively. The interaction between them with α-glucosidase were mainly driven by hydrophobic interaction, they induced conformational changes of α-glucosidase. The human α-glucosidase (C-terminal maltase-glucoamylase, GH31) was used in the molecular docking analysis to determine the interaction of eriocitrin and eriodictyol with the α-glucosidase. The results revealed that they could bind with α-glucosidase and might cause the decrease of α-glucosidase activity. The inhibitory effect of eriocitrin was stronger than that of eriodictyol, which might be due to the position and amount of hydroxyl groups. This work confirmed two novel α-glucosidase inhibitors and provided the structure-function relationship of flavonoids in inhibition of α-glucosidase activity. [ABSTRACT FROM AUTHOR]

Eriocitrin (EC) is an abundant flavonoid in lemons, which is known as a strong antioxidant agent. This study investigated the biological and molecular mechanisms underlying the anti-obesity effect of EC in high-fat diet (HFD)-fed obese mice. C57BL/6N mice were fed an HFD (40 kcal% fat) with or without 0.005% (w/w) EC for 16 weeks. Dietary EC improved adiposity by increasing adipocyte fatty acid (FA) oxidation, energy expenditure, and mRNA expression of thermogenesis-related genes in brown adipose tissue (BAT) and skeletal muscle, whereas it also decreased lipogenesis-related gene expression in white adipose tissue. In addition to adiposity, EC prevented hepatic steatosis by diminishing lipogenesis while enhancing FA oxidation in the liver and fecal lipid excretion, which was linked to attenuation of hyperlipidemia. Moreover, EC improved insulin sensitivity by decreasing hepatic gluconeogenesis and proinflammatory responses. These findings indicate that EC may protect against diet-induced adiposity and related metabolic disorders by controlling thermogenesis of BAT and skeletal muscle, FA oxidation, lipogenesis, fecal lipid excretion, glucose utilization, and gluconeogenesis. [ABSTRACT FROM AUTHOR]

The intake of hesperidin-rich sources, mostly found in orange juice, can decrease cardiometabolic risk, potentially linked to the gut microbial phase-II hesperetin derivatives. However, the low hesperidin solubility hampers its bioavailability and microbial metabolism, yielding a high inter-individual variability (high vs. low-producers) that prevents consistent health-related evidence. Contrarily, the human metabolism of (lemon) eriocitrin is hardly known. We hypothesize that the higher solubility of (lemon) eriocitrin vs. (orange) hesperidin might yield more bioavailable metabolites than hesperidin. A randomized-crossover human pharmacokinetic study (n = 16) compared the bioavailability and metabolism of flavanones from lemon and orange extracts and postprandial changes in oxidative, inflammatory, and metabolic markers after a high-fat-high-sugars meal. A total of 17 phase-II flavanone-derived metabolites were identified. No significant biomarker changes were observed. Plasma and urinary concentrations of all metabolites, including hesperetin metabolites, were higher after lemon extract intake. Total plasma metabolites showed significantly mean lower Tmax (6.0 ± 0.4 vs. 8.0 ± 0.5 h) and higher Cmax and AUC values after lemon extract intake. We provide new insights on hesperetin-eriodictyol interconversion and naringenin formation from hesperidin in humans. Our results suggest that regular consumption of a soluble and eco-friendly eriocitrin-rich lemon extract could provide a circulating concentration metabolites threshold to exert health benefits, even in the so-called low-producers.

Eriocitrin is a flavanone glycoside which exists in lemon or lime citrus fruits. It exhibits antioxidant, anti-cancer and anti-allergy activities. β-casein is important protein in bovine milk, under appropriate conditions, it can form stable micelle like structures in aqueous solution, which is beneficial to the nutritional ingredient transportation in body. In this work, the interaction mechanisms of eriocitrin with β-casein under physiological conditions (pH = 7.4) were investigated by utilizing multi-spectroscopic techniques and molecular docking methods. The endogenous fluorescence of β-casein was quenched by the interaction with eriocitrin and the quenching mode was static quenching. The interaction of eriocitrin with β-casein was a spontaneous reaction principally driven by hydrophobic interaction. At 310 K , the binding constant was equal to 6.68 × 105 L mol−1 and the number of binding sites was approximately equal to 1. The changes of β-casein conformation were confirmed by FTIR, circular dichroism spectroscopy and synchronous fluorescence spectroscopy. Moreover, molecular docking studies illustrated the most possible binding position of eriocitrin on β-casein. The binding interaction of eriocitrin with β-casein nanoparticles under physiological conditions (pH = 7.4) was studied by multi-spectroscopic and molecular docking methods. Image 1 • Eriocitrin binds to the hydrophobic core of β-casein. • Hydrophobic interaction are predominating in binding process. • β-casein might act as a as transporter for the delivery of eriocitrin. [ABSTRACT FROM AUTHOR]

Eriocitrin is a flavonoid that is isolated from orange peel. Resveratrol is a polyphenol compound, which is present in various fruits, such as grapes. The aim of the present study was to investigate both in vitro and in vivo anti-inflammatory effects of eriocitrin combined with resveratrol using lipopolysaccharide (LPS)-induced RAW264.7 cells and a mouse model of ear edema. The results showed that eriocitrin combined with resveratrol strongly inhibited LPS-induced secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and Interleukin-1β (IL-1β). Moreover, Eriocitrin combined with resveratrol potently inhibited nuclear factor-κB (NF-κB), phosphor-STAT3, and phosphor-AKT, which was accompanied by inhibition of phosphorylation in mitogen-activated protein kinase (MAPK) signaling pathways. Treatment with eriocitrin combined with resveratrol alleviated edema and subcutaneous tissue inflammation caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) in vivo. This study also demonstrated that treatment with eriocitrin and resveratrol decreased the levels of the pro-inflammatory cytokines TNF-α and IL-1β. The results of the present study indicate that eriocitrin combined with resveratrol effectively inhibits inflammatory responses both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Phenolics and essential oil of peppermint were obtained by pressurized hot water extraction (PHWE). The best extraction conditions were found to be 130 °C for temperature, 10 min for extraction time, and 3 cycles for extraction number. There were no statistically significant differences between 130 and 160 °C in terms of essential oil content. Total phenolic contents (TPC) of the extracts were higher at 160 °C than that of 130 °C. However, further HPLC analysis of the extracts revealed that hydrolysis and/or decomposition of phenolics were observed in the extracts obtained at 160 °C. The main phenolic of peppermint was determined as eriocitrin by HPLC-DAD, while menthol was the dominant component in essential oil fraction of peppermint by GC-FID. The present study demonstrated that PHWE was a suitable technique for simultaneous extraction of phenolics and essential oil from peppermint. The technique might be used as an analytical extraction tool for determination of phenolics and essential oil. Moreover, the extracts of PHWE could directly be evaluated for the enrichment of liquid food formulations or be transformed into solid form by suitable techniques such as spray drying for easy storage and subsequent enrichment of food products. [ABSTRACT FROM AUTHOR]

A novel electrochemically activated nanocomposite, CoS 2 Nanoparticles and MoS 2 Nanosheets decorated poly(diallyldimethylammonium chloride)-functionalized graphene (CoS 2 -MoS 2 -PDDA-GR), was successfully synthesized through a simple and low-cost method. X-ray diffraction (XRD), Transmission electron microscopy (TEM), Electrochemical impedance spectroscopy (EIS) and Cyclic voltammetry (CV) techniques were used to characterize the nanocomposites. Based on the CoS 2 -MoS 2 -PDDA-GR nanocomposite modified glassy carbon electrode, the electrochemical properties of eriocitrin were investigated in detail and a sensitive determinative method was established synchronously. Compared with others, this sensor exhibited larger effective surface area, more reactive site and excellent voltammetric response for eriocitrin. Under optimum conditions by DPV, the oxidation peak currents responded to eriocitrin linearly over a concentration range from 2.0 × 10 −9 to 1.0 × 10 −6 mol L −1 with a detection limit of 6.7 × 10 −10 mol L −1 (S/N = 3). In addition, this fabricated sensor was successfully applied to detect eriocitrin in real samples with satisfactory results. [ABSTRACT FROM AUTHOR]

Recently, several studies have highlighted the role of Citrus flavanones in counteracting oxidative stress and inflammatory response in bowel diseases. The aim of study was to identify the most promising Citrus flavanones by a preliminary antioxidant and anti-inflammatory screening by in vitro cell-free assays, and then to mix the most powerful ones in equimolar ratio in order to investigate a potential synergistic activity. The obtained flavanones mix (FM) was then subjected to in vitro simulated digestion to evaluate the availability of the parent compounds at the intestinal level. Finally, the anti-inflammatory activity was investigated on a Caco-2 cell-based model stimulated with interleukin (IL)-1β. FM showed stronger antioxidant and anti-inflammatory activity with respect to the single flavanones, demonstrating the occurrence of synergistic activity. The LC-DAD-ESI-MS/MS analysis of gastric and duodenal digested FM (DFM) showed that all compounds remained unchanged at the end of digestion. As proof, a superimposable behavior was observed between FM and DFM in the anti-inflammatory assay carried out on Caco-2 cells. Indeed, it was observed that both FM and DFM decreased the IL-6, IL-8, and nitric oxide (NO) release similarly to the reference anti-inflammatory drug dexamethasone.

Introduction: Lung adenocarcinoma (LUAD) is the most prevalent pathological subtype of non-small cell lung cancer (NSCLC), characterized by a high propensity for relapse and metastasis due to epithelial-mesenchymal transition (EMT) of cancer cells. Ferroptosis, a newly discovered regulated cell death modality, is interconnected with the EMT process in certain cancers. Eriocitrin, a natural flavonoid compound, exerts anti-inflammatory and anticancer effects., Objectives: The aim of this study is to investigate the potential inhibitory effect of eriocitrin on lung adenocarcinoma metastasis and explore whether its underlying mechanism involves ferroptosis induction in cancer cells., Methods: The CCK8 assay and wound healing assay and transwell were conducted to determine the cell viability and migration ability of A549 and H1299 cells, respectively. EMT process was assessed by western blot and RT-PCR to detect protein and mRNA levels of EMT markers. ROS and cell iron were measured to determine ferroptosis level., Results: Eriocitrin treatment significantly inhibited cell viability and migration ability in a concentration-dependent manner. Furthermore, eriocitrin administration for 24 hours resulted in enhanced expression of E-cadherin, while downregulating vimentin, N-cadherin and snail expression, indicating marked repression of the EMT process. Additionally, eriocitrin significantly induced ferroptosis in A549 and H1299 cells, as evidenced by increased ROS levels, downregulation of Nrf-2, SLC7A11 and GPX4 expression, and enhanced cellular iron accumulation. Moreover, pretreatment with the ferroptosis inhibitor ferrostatin-1 effectively abrogated the inhibitory effects of eriocitrin on EMT., Conclusions: Our findings further support the anti-cancer properties of eriocitrin, as evidenced by its ability to inhibit the EMT process in LUAD cells, which is partially mediated through induction of ferroptosis in cancer cells.

[Display omitted] • Eriocitrin can alleviate sepsis-induced acute lung injury in mice. • Eriocitrin can reduce oxidative stress and inflammation via inhibiting glycolysis in ALI mice and primary peritoneal macrophage. • Eriocitrin treated septic ALI through regulating MKP1/MAPK pathway mediated-glycolysis. • The study provides a potentially promising idea using native compound for clinical prophylaxis of sepsis-induced ALI. Metabolic reprogramming has been shown to aggravate sepsis-induced acute lung injury. In particular, enhanced glycolysis is closely associated with inflammation and oxidative stress. Eriocitrin (ERI) is a natural flavonoid found in citrus fruit that exhibits various pharmacological activities, with antioxidant, anti-inflammatory, anti-diabetic, and anti-tumor properties. However, the role of ERI in lung injury is not well understood. We established a septic mouse model of acute lung injury (ALI) using lipopolysaccharide (LPS) for induction. Primary peritoneal macrophages were isolated to verify the relevant molecular mechanism. Tissues were assessed for lung pathology, pro-inflammatory cytokines, markers of oxidative stress, and protein and mRNA expression levels. In vivo experiments showed that ERI effectively alleviated LPS-induced pathological injury, suppress the inflammatory response (TNF-α, IL-1β, IL-6 levels) and decreased oxidative stress (MDA, ROS) in murine lung tissue. In vitro, ERI increased the resistance of LPS-treated cells to excessive inflammation and oxidative stress by inhibiting the enhancement of glycolysis (indicated by expression levels of HIF-1α, HK2, LDHA, PFKFB3, and PKM2). Specifically, the beneficial effects of ERI following LPS-induced lung injury occurred through promoting the expression of MKP1, which mediates the inactivation of the MAPK pathway to inhibit enhanced glycolysis. These results demonstrate that ERI has a protective effect on sepsis-induced ALI by regulating MKP1/MAPK pathway mediated-glycolysis. Hence, ERI is a promising candidate against ALI via inhibiting glycolysis. [ABSTRACT FROM AUTHOR]

Lemon processing generates thousands of tons of residues that can be preserved as flours by thermal treatment to obtain phenolic compounds with beneficial bioactivities. In this study, the effect of different drying temperatures (40, 50, 60, 70, 80, 90, 100 and 110 °C) on the Total Phenolic Content (TPC), antioxidant and antimicrobial activities of phenolic compounds present in Citrus. lemon (L.) Burn f waste was determined. Identification and quantification of phenolic compounds were also performed by UPLC-PDA and UPLC-ESI-MS analysis. Eriocitrin (19.79−27.29 mg g−1 DW) and hesperidin (7.63−9.10 mg g−1 DW) were detected as the major phenolic compounds in the flours by UPLC-PDA and confirmed by UPLC-ESI-MS. Antimicrobial activity determined by Minimum Inhibitory Concentration (MIC) against Salmonella typhimurium, Escherichia coli and Staphylococcus aureus was observed. Accordingly, a stable functional flour as a source of bioactive phenolic compounds obtained from lemon residues at 50 °C may be produced as a value-added product useful in various industrial sectors.

A new graphene nanocomposite, CeO 2 -poly(diallyldimethylammonium chloride)-graphene (CeO 2 -PDDA-GR), was prepared by an easy and low-cost hydrothermal method. The images of transmission electron microscopy (TEM) showed that well-shaped CeO 2 nanoparticles distributed more uniformly on the GR sheets. Based on the CeO 2 -PDDA-GR composites modified glassy carbon electrode, the electrochemical properties of eriocitrin were investigated in detail and a sensitive determination method was established synchronously. Differential pulse voltammetry (DPV) measurement revealed that the oxidation peak current increased linearly with eriocitrin concentrations in range of 1.0 × 10 − 8 mol L − 1 –1.0 × 10 − 6 mol L − 1 with detection limit of 7.0 × 10 − 10 mol L − 1 (S/N = 3). Moreover, the proposed method was used in determination of eriocitrin in lemon sample with accurate results. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is a lethal cancer with high recurrence ratio and lacks effective therapeutics. In the past few years, it has been reported that increased intake of vegetables and fruits could reduce the cancer incidence, which suggests dietary agents might possess anticancer effects. Eriocitrin is a flavonoid isolated from lemon, which is known as a strong antioxidant agent. We here for the first time demonstrated that eriocitrin could inhibit the proliferation of hepatocellular carcinoma cell lines by arresting cell cycle in S phase through up-regulation of p53, cyclin A, cyclin D3 and CDK6. Furthermore, we found that eriocitrin could trigger apoptosis by activating mitochondria-involved intrinsic signaling pathway. Thus, eriocitrin might be regarded as a potential chemopreventive natural product to inhibit the early malignant transformation of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]