Flavonoids Hesperidin Research Articles

Flavonoid hesperidin protects neural crest cells from death caused by aflatoxin B1

The neural crest (NC) corresponds to a collection of multipotent and oligopotent progenitors endowed with both neural and mesenchymal potentials. The derivatives of the NC at trunk level include neurons and glial cells of the peripheral nervous system. Despite the well-known influence of aflatoxins on the development of cancer, the issue of whether they also influence NC cells has not been yet addressed. In the present work, we have investigated the effects of aflatoxin B(1) on quail NC cells and the concomitant effects of the flavonoid hesperidin associated with this mycotoxin. We show for the first time that aflatoxin B(1) decreases the viability and the total number of glial and neuronal cells/field, although their proportions in relation to the total number of cells were not altered. Therefore, aflatoxin has no effect on NC differentiation. However, this compound was able to reduce NC proliferation and NC survival. Furthermore, the co-administration of hesperidin, a well-known polyphenolic protector of cell death, partially prevented the effect of aflatoxin B(1) . Taken together, our results demonstrate that aflatoxin B(1) is toxic to NC cells, an effect partially prevented by the flavonoid hesperidin. This study may contribute to the understanding of the effects of these compounds during early embryonic development and offer potentially more assertive diets and treatments for pregnant animals.

The flavonoids hesperidin and rutin promote neural crest cell survival

The neural crest (NC) corresponds to a collection of multipotent and oligopotent progenitors endowed with both neural and mesenchymal potentials. The derivatives of the NC at trunk level include neurons and glial cells of the peripheral nervous system in addition to melanocytes, smooth muscle cells and some endocrine cells. Environmental factors control the fate decisions of NC cells. Despite the well-known influence of flavonoids on the central nervous system, the issue of whether they also influence NC cells has not been yet addressed. Flavonoids are polyphenolic compounds that are integral components of the human diet. The biological activities of these compounds cover a very broad spectrum, from anticancer and antibacterial activities to inhibition of bone reabsorption and modulation of inflammatory response. In the present work, we have investigated the actions of the flavonoids hesperidin, rutin and quercetin on NC cells of quail, in vitro. We show for the first time, that hesperidin and rutin increase the viability of trunk NC cells in culture, without affecting cell differentiation and proliferation. The molecular mechanism of this action is dependent on ERK2 and PI3K pathways. Quercetin had no effect on NC progenitors. Taken together, these results suggest that flavonoids hesperidin and rutin increase NC cell survival, which may be useful against the toxicity of some chemicals during embryonic development.

Effects of the flavonoid hesperidin in cerebral cortical progenitors in vitro: indirect action through astrocytes

Flavonoids are polyphenolic compounds that are integral components of the human diet, universally present as constituents of fruits and vegetables as well as plant-derived foods and beverages such as oil, tea, and red wine. The biological activities of flavonoids cover a very broad spectrum, from anticancer and antibacterial activities to inhibition of bone reabsorption and modulation of inflammatory response. Although emerging evidence has suggested that flavonoids might have an impact on brain pathology and aging, their role as a mediator in interactions between neurons and glial cells has been poorly explored. In the present work, we have performed a screening of flavonoid actions by analyzing the effects of hesperidin, quercetin and rutin on murine cerebral cortex astrocytes and neural progenitors. Treatment of astrocytes with flavonoids did not interfere with cell viability and proliferation. However a culture of neural progenitors with conditioned medium from hesperidin treated-astrocyte (H-CM) yielded produced a 41% and 25% increase in the number of neural progenitors and post-mitotic neurons, respectively. The H-CM effect was mainly due to modulation of neuronal progenitor survival. Pools of astrocyte and oligodendrocyte progenitors were not affected by H-CM (hesperidin), Q-CM (quercetin) and R-CM (rutin). Q-CM and R-CM did not increase neuronal population. These results suggest that H-CM might be composed by a new factor that could modulate neuroglial interactions during central nervous system development and opens the possibility for using flavonoids as new therapeutic strategies for neurodegenerative diseases.

Flavonoids inhibit high glucose-induced up-regulation of ICAM-1 via the p38 MAPK pathway in human vein endothelial cells

Recently, several flavonoids have been shown to have cardioprotective, cancer preventive, or anti-inflammatory properties. However, the specific mechanisms underlying their protective effects remain unclear. We aimed to investigate the different effects of three representative flavonoids—hesperidin, naringin, and resveratrol—on intracellular adhesion molecule-1 (ICAM-1) induction in human umbilical vein endothelial cells (HUVECs) by using high-glucose (HG) concentrations and the possible underlying molecular mechanisms. In HG-induced HUVEC cultures, the effects of three different flavonoids on ICAM-1 production and p38 phosphorylation were examined in the presence or absence of inhibitors targeting the mitogen-activated protein kinase (MAPK) signal transduction pathway. HG stimulation of HUVECs increased the levels of the adhesion molecules ICAM-1 and endothelial selectin (E-selectin). Pretreatment with all the three flavonoids drastically inhibited ICAM-1 expression in a time-dependent manner, but did not alter VCAM-1 and E-selectin expressions. Moreover, we investigated the effects of flavonoids on the MAPK signal transduction pathway, because MAPK families are associated with vascular inflammation under stress. These flavonoids did not block HG-induced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but completely inhibited the HG-induced phosphorylation of p38 MAPK. SB202190, an inhibitor of p38 MAPK, also inhibited the HG-induced enrichment of ICAM-1. This study demonstrated that hesperidin, naringin, and resveratrol reduced the HG-induced ICAM-1 expression via the p38 MAPK signaling pathway, contributing to the inhibition of monocyte adhesion to endothelial cells.

Therapeutic effect of hesperidin with reference to biotransformation, lysosomal and mitochondrial TCA cycle enzymes against 7,12-dimethylbenz(a)anthracene-induced experimental mammary cellular carcinoma

The present study was aimed to investigate the therapeutic effect of hesperidin with reference to hepatic biotransformation, lysosomal and mitochondrial TCA cycle enzymes against 7,12-dimethylbenz(a)anthracene (DMBA)-induced experimental breast cancer. DMBA is a major class of chemical carcinogen present in the environment and it may increase breast cancer risk. In the present investigation, 7,12-DMBA was used as a carcinogen to induce breast cancer in rats. Hesperidin, a natural flavanoglycoside has demonstrated a wide variety of biological activities which make it a good candidate for the treatment of many oxidative stress-mediated diseases. In this study the hepatic biotransformation (Phase I, Phase II) enzymes were analyzed both in breast and liver. The lysosomal enzymes were analyzed in breast tissues and the key mitochondrial TCA cycle enzymes were analyzed in liver. The results revealed that treatment with hesperidin (30 mg/kg body weight) significantly restored all the altered biochemical parameters. The ultra structural analysis of breast and histology of liver tissues inevitably supports the biochemical alterations and this was attributed due to the interaction of flavonoid hesperidin through the induction or inhibition of metabolism and also the modulating property in the lysosomal and TCA cycle compartments.

Hesperidin, a Flavone Glycoside, as Mediator of Neuronal Survival

Flavonoids comprise the most common group of plant polyphenols and provide much of the flavor and color to fruits and vegetables. More than 5,000 different flavonoids have been described. The biological activities of flavonoids cover a very broad spectrum, from anticancer and antibacterial activities to inhibition of bone reabsorption and neuroprotection effect. Although emerging evidence suggests that flavonoids have an important role on brain development, little is known about their mechanisms of action. In the present work, we performed a screening of flavonoid actions by analyzing the effects of these substances (hesperidin and rutin) on neural progenitors and neuronal morphogenesis in vitro. We demonstrated that treatment of neural progenitors with the flavonoid hesperidin enhanced neuronal population as revealed by an 80% increase in the number of β-tubulin III cells. This effect was mainly due to modulation of neuronal progenitor survival. Pools of astrocyte and oligodendrocyte progenitors were not affected by hesperidin whereas rutin had no effect on neuronal population. We also demonstrated that the flavonoid hesperidin modulates neuronal cell death by activating MAPK and PI3K pathways. This opens the possibility of using flavonoids for potential new therapeutic strategies for neurodegenerative diseases.

The citrus flavonoid hesperidin induces p53 and inhibits NF-κB activation in order to trigger apoptosis in NALM-6 cells: involvement of PPARγ-dependent mechanism

Hesperidin, a flavanone present in citrus fruits, has been identified as a potent anticancer agent because of its proapoptotic and antiproliferative characteristics in some tumor cells. However, the precise mechanisms of action are not entirely understood. The main purpose of this study is to investigate the involvement of peroxisome proliferator-activated receptor-gamma (PPARγ) in hesperidin's anticancer actions in human pre-B NALM-6 cells, which expresses wild-type p53. The effects of hesperidin on cell-cycle distribution, proliferation, and caspase-mediated apoptosis were examined in NALM-6 cells in the presence or absence of GW9662. The expression of peroxisome proliferator-activated receptor-gamma (PPARγ), p53, phospho-IκB, Bcl-2, Bax, and XIAP proteins were focused on using the immunoblotting assay. The transcriptional activities of PPARγ and nuclear factor-kappaB (NF-κB) were analyzed by the transcription factor assay kits. The expression of PPARγ and p53 was analyzed using the RT-PCR method. Hesperidin induced the expression and transcriptional activity of PPARγ and promoted p53 accumulation and downregulated constitutive NF-κB activity in a PPARγ-dependent and PPARγ-independent manner. The growth-inhibitory effect of hesperidin was partially reduced when the cells preincubated with PPARγ antagonist prior to the exposure to hesperidin. The findings of this study clearly demonstrate that hesperidin-mediated proapoptotic and antiproliferative actions are regulated via both PPARγ-dependent and PPARγ-independent pathways in NALM-6 cells. These data provide the first evidence that hesperidin could be developed as an agent against hematopoietic malignancies.

Analysis of flavonoids by capillary zone electrophoresis with electrokinetic supercharging

On-line concentration via Electrokinetic Supercharging (EKS) was used to enhance the sensitivity of the capillary electrophoretic separation of the four flavonoids naringenin, hesperetin, naringin and hesperidin. Separation conditions, including the background electrolyte pH and concentration, the length and choice of terminator and the electrokinetic injection time were optimized. The optimum conditions were: a background electrolyte of 30 mM sodium tetraborate (pH 9.5) containing 5% (v/v) of methanol, electrokinetic injection of the sample (130 s, -10 kV) followed by hydrodynamic injecting of 100 mM 2-(cyclohexylamino)ethanesulfonic acid (CHES) (17 s, 0.5 psi) as terminator, and separation with -20 kV. Under these conditions the four flavonoids could be separated with a sample-to-sample time of 15 min and detection limits from 2.0 to 6.8 ng mL(-1). When compared to a conventional hydrodynamic injection the sensitivity was enhanced between 824 and 1515 times which is 7.6-16 times higher than other CE methods for the on-line concentration of flavonoids. The applicability of the developed method was demonstrated by the detection of the four flavonoids in an aqueous extract of Clematis hexapetala pall.

The Citrus Flavonoids Hesperidin and Naringin Do Not Affect Serum Cholesterol in Moderately Hypercholesterolemic Men and Women1–3

The citrus flavonoids hesperidin and naringin have been suggested to lower blood total (TC) and LDL-cholesterol (LDL-C) both in animal models and humans. However, the evidence from previous studies in humans is not convincing. This study evaluated the LDL-C–lowering efficacy of pure hesperidin and naringin in moderately hypercholesterolemic individuals. A total of 204 healthy men and women with a serum TC concentration of 5.0–8.0 mmol/L participated in a randomized, placebo-controlled, parallel trial with 3 groups. A 4-wk preintervention period during which participants refrained from consuming hesperidin and naringin sources preceded the intervention. During the 4-wk intervention, the participants applied the same dietary restrictions and consumed 4 capsules/d providing either placebo (cellulose) or a daily dose of 800 mg hesperidin or 500 mg naringin. Blood samples to measure serum lipids were taken on 2 consecutive days at the beginning and end of the intervention phase. One hundred ninety-four participants completed the study. They maintained their prestudy body weights (mean changes lt 0.2 kg in all groups). In all groups, the mean consumption of scheduled capsules was gt 99%. Hesperidin and naringin did not affect TC or LDL-C, with endpoint LDL-C concentrations (adjusted for baseline) of 4.00 ± 0.04, 3.99 ± 0.04, and 3.99 ± 0.04 mmol/L for control, hesperidin, and naringin groups, respectively. These citrus flavonoids also did not affect serum HDL-cholesterol and triglyceride concentrations. In conclusion, pure hesperidin and naringin consumed in capsules at mealtime do not lower serum TC and LDL-C concentrations in moderately hypercholesterolemic men and women.

Introduction of Distillate Rosemary Leaves into the Diet of the Murciano-Granadina Goat: Transfer of Polyphenolic Compounds to Goats' Milk and the Plasma of Suckling Goat Kids

The effect of the introduction of distilled rosemary leaves into the diet of the Murciano-Granadina goat on the polyphenolic profile of the goats' milk during the physiological stages of gestation and lactation was studied. The inclusion of rosemary leaves into the animal diet modified neither animal productivity (milk yield) nor milk quality. The following components were found in increased concentration (P < 0.05) in the goats' milk after the introduction of rosemary leaves into their diet: flavonoids hesperidin, naringin, and genkwanin; gallic acid; and phenolic diterpenes carnosol and carnosic acid. With regard to the transfer of polyphenols to the plasma of the suckling goat kid, a statistically significant increase (P < 0.05) in rosmarinic acid, carnosic acid, and carnosol concentrations was detected. From this point of view, distillate rosemary leaves can be proposed as an ingredient in ruminant feed because they both alter neither the yield nor the quality of Murciano-Granadina goats' milk and allow for an increased concentration of polyphenolic components in the goats' milk and in the plasma of the suckling goat kid.

Extracellular monoenzyme deglycosylation system of 7-O-linked flavonoid β-rutinosides and its disaccharide transglycosylation activity from Stilbella fimetaria

We screened for microorganisms able to use flavonoids as a carbon source; and one isolate, nominated Stilbella fimetaria SES201, was found to possess a disaccharide-specific hydrolase. It was a cell-bound ectoenzyme that was released to the medium during conidiogenesis. The enzyme was shown to cleave the flavonoid hesperidin (hesperetin 7-O-alpha-rhamnopyranosyl-beta-glucopyranoside) into rutinose (alpha-rhamnopyranosyl-beta-glucopyranose) and hesperetin. Since only intracellular traces of monoglycosidase activities (beta-glucosidase, alpha-rhamnosidase) were produced, the disaccharidase alpha-rhamnosyl-beta-glucosidase was the main system utilized by the microorganism for hesperidin hydrolysis. The enzyme was a glycoprotein with a molecular weight of 42224 Da and isoelectric point of 5.7. Even when maximum activity was found at 70 degrees C, it was active at temperatures as low as 5 degrees C, consistent with the psychrotolerant character of S. fimetaria. Substrate preference studies indicated that the enzyme exhibits high specificity toward 7-O-linked flavonoid beta-rutinosides. It did not act on flavonoid 3-O-beta-rutinoside and 7-O-beta-neohesperidosides, neither monoglycosylated substrates. In an aqueous medium, the alpha-rhamnosyl-beta-glucosidase was also able to transfer rutinose to other acceptors besides water, indicating its potential as biocatalyst for organic synthesis. The monoenzyme strategy of Acremonium sp. SES201 = DSM 24697, [corrected] as well as the enzyme substrate preference for 7-O-beta-flavonoid rutinosides, is unique characteristics among the microbial flavonoid deglycosylation systems reported.

Suppression of adjuvant arthritis by hesperidin in rats and its mechanisms

The citrus flavonoid hesperidin has been reported to possess a wide range of pharmacological properties. We have investigated the preventive and therapeutic effects of hesperidin on the development of adjuvant arthritis (AA), a rat model of rheumatoid arthritis (RA). Freund's complete adjuvant was used to induce AA in rats. Secondary paw swelling, polyarthritis index and histopathological assessment of ankle joints were used to evaluate the effects of hesperidin on AA rats. Concanavalin-A-induced T-lymphocyte proliferation and interleukin (IL)-2 production by splenocytes were measured using the MTT assay. Levels of IL-1, IL-6 and tumour necrosis factor (TNF)-alpha secreted by peritoneal macrophages (PM) were measured by RIA. Intragastric administration of hesperidin significantly attenuated secondary paw swelling and reduced the polyarthritis index of AA rats in a dose-dependent manner. In addition, hesperidin clearly ameliorated the pathological changes in AA rats. Hesperidin also restored the suppression of T-lymphocyte proliferation and IL-2 production, and downregulated production of IL-1, IL-6 and TNF-alpha by PM in AA rats. Our results suggest that hesperidin improves AA by downregulating the function of over-active macrophages and by up-regulating the activities of dysfunctional T lymphocytes. Hesperidin may therefore have therapeutic value for the clinical treatment of RA. Further research is required to clarify the detailed mechanisms of the protective effects of hesperidin on AA.

Effect of adding citrus waste water, thyme and oregano essential oil on the chemical, physical and sensory characteristics of a bologna sausage

Abstract The industrial transformation of citrus fruits generates large quantities of co-products rich in bioactive compounds that may well be suitable for other purposes. One such co-product is the water used in the process of obtaining fibre from orange. It was found that the addition of citrus waste water (5–10%) obtained as co-product during the extraction of dietary fibre and oregano or thyme essential oils (0.02%) to the bologna samples reduced the residual nitrite levels and the degree of lipid oxidation. The flavonoids hesperidin and narirutin were detected in all the samples, while those prepared with 5% of citrus waste water and 0.02% of either essential oil were the most highly valued from a sensory point of view. Industrial relevance The object of the present work was to study the effect of adding different concentrations (5–10%) of orange juice waste water obtained as co-product during the extraction of dietary fibre, and oregano or thyme essential oils (0.02%), on the chemical, physicochemical and sensory characteristics of a bologna-type sausage, to extend its shelf life. Addition of orange juice waste water and spices essential oil had a significant effect on shelf-life extension because of a reduction of the lipid oxidation degree.

Effects of pressure homogenization on particle size and the functional properties of citrus juices

Homogenization is useful in the citrus industry to improve the quality of citrus juices. The aim of this work was to study the effect of the homogenization pressures 0, 5, 10, 15, 20, 25 and 30 MPa on the particle size distribution, colour, cloudiness, and flavonoid content of fresh citrus juices to determine the ideal conditions of juices to be used in the development of functional fresh fruit. The results showed that homogenization pressure affected the particle size distribution and colour of the citrus juices, which made it possible to define different sample groups on the basis of the applied pressure. In fresh juice the contents of the flavonoids were not affected by homogenization pressure but after five months stored juice the content of the flavonoid hesperidin was affected..

10.1007/s11828-008-1008-x

A comparative kinetic study of ortho-phenylenediamine (PDA) oxidation in the "pseudoperoxidase" system Methemalbumin-H2O2 in the presence of 2-amino-4-tret-butylphenol (ATBP), 2-amino-4,6-di-tret-butylphenol (ADTBP) and its four N-acyl derivates, as well as flavonoids (quercetin, morin, silibin, hesperidin and naringin) has been carried out under standart conditions at 20 degrees C in phosphate buffered saline, pH 7.4, containing 5.25% ethanol and DMFA. ATBP, ADTBP and two its N-acyl-derivatives as well as all five flavonoids inhibited with different efficiency the PDA oxidation characterized in terms of the inhibition constants, K(i), M, or the percent of inhibition degree at the maximal taking concentrations of these inhibitors. Most effective antioxidants were quercetin (K(i) = 7.7x10(-5) M) and ATBP (K(i) = 1.26x10(-4) M). Using these characteristics and other necessary criteria, the pairs PDA-quercetin and PDA-ATBP were proposed for a practical application in the test-systems for total antioxidant activity of biological objects.

Antioxidant effects of the VO(IV) hesperidin complex and its role in cancer chemoprevention

Vanadium compounds are known for a variety of pharmacological properties. Many of them display antitumoral and osteogenic effects in several cell lines. Free radicals induce the development of tumoral processes. Natural polyphenols such as flavonoids have antioxidant properties since they scavenge different free radicals. For these reasons it is interesting to investigate the effects of a new complex generated between the vanadyl(IV) cation and the flavonoid hesperidin. The complex has been synthesized and characterized by physicochemical methods. Spectroscopic analysis revealed a 1:1 stoichiometry of ligand:VO and coordination by deprotonated cis-hydroxyl groups to the disaccharide moiety of the ligand. The complex improves the superoxide dismutase (SOD)-like activity of the ligand, but the scavenging of other radicals tested does not change upon complexation. When tested on two tumoral cell lines in culture (one of them derived from a rat osteosarcoma UMR106 and the other from human colon adenocarcinoma Caco-2), the complex enhanced the antiproliferative effects of the free ligand, and this effect correlated with the morphological alterations toward apoptosis. Also, on the osteoblastic cell line the complex stimulated cell proliferation and collagen type I production at low concentrations. At higher doses the complex behaved as a cytotoxic compound for the osteoblasts.

Interaction of the flavonoid hesperidin with bovine serum albumin: A fluorescence quenching study

Abstract The interaction between the flavonoid hesperidin and bovine serum albumin (BSA) was investigated by fluorescence and UV/Vis absorption spectroscopy. The results revealed that hesperidin caused the fluorescence quenching of BSA through a static quenching procedure. The hydrophobic and electrostatic interactions play a major role in stabilizing the complex. The binding site number n , and apparent binding constant K A , corresponding thermodynamic parameters Δ G o , Δ H o , Δ S o at different temperatures were calculated. The distance r between donor (BSA) and acceptor (hesperidin) was obtained according to fluorescence resonance energy transfer. The effect of Cu 2+ , Zn 2+ , Ni 2+ , Co 2+ , and Mn 2+ on the binding constants between hesperidin and BSA were studied. The effect of hesperidin on the conformation of BSA was analyzed using synchronous fluorescence spectroscopy and UV/Vis absorption spectroscopy.

Suppression of Collagen-Induced Arthritis by Oral Administration of theCitrusFlavonoid Hesperidin

The preventive and therapeutic effects of the Citrus flavonoid hesperidin (HES) on the development of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA), were investigated. Mice were administered orally HES three times a week starting from either the onset (day 21) of secondary immunization or on day 31, when the CIA development had reached a plateau. In both cases, treatment with HES resulted in a significant suppression of clinical scores and improvement of histological features. These results suggest that oral administration of HES could be effective for treating human RA patients.

Bioavailability Is Improved by Enzymatic Modification of the Citrus Flavonoid Hesperidin in Humans: A Randomized, Double-Blind, Crossover Trial

Hesperidin is the predominant polyphenol consumed from citrus fruits and juices. However, hesperidin is proposed to have limited bioavailability due to the rutinoside moiety attached to the flavonoid. The aim of this study was to demonstrate in human subjects that the removal of the rhamnose group to yield the corresponding flavonoid glucoside (i.e., hesperetin-7-glucoside) will improve the bioavailability of the aglycone hesperetin. Healthy volunteers (n=16) completed the double-blind, randomized, crossover study. Subjects randomly consumed hesperetin equivalents supplied as orange juice with natural hesperidin ("low dose"), orange juice treated with hesperidinase enzyme to yield hesperetin-7-glucoside, and orange juice fortified to obtain 3 times more hesperidin than naturally present ("high dose"). The area under the curve (AUC) for total plasma hesperetin of subjects consuming hesperetin-7-glucoside juice was 2-fold higher than that of subjects consuming the "low" dose hesperidin juice [3.45+/-1.27 vs. 1.16+/-0.52 mmol/(L.h), respectively, P>0.0001]. The AUC for hesperetin after consuming the hesperetin-7-glucoside juice was improved to the level of the "high" dose hesperidin juice [4.16+/-1.50 mmol/(L.h)]. The peak plasma concentrations (C(max)) of hesperetin were 4-fold higher (2.60+/-1.07 mmol/L, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with those consuming "low" dose hesperidin juice (0.48 +/- 0.27 mmol/L), and 1.5-fold higher than those consuming "high" dose hesperidin juice (1.05+/-0.25 mmol/L). The corresponding T(max) was much faster (0.6+/-0.1 h, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with "low" dose (7.0+/-3.0 h) and "high" dose (7.4+/-2.0 h) hesperidin juices. The results of this study demonstrated that the bioavailability of hesperidin was modulated by enzymatic conversion to hesperetin-7-glucoside, thus changing the absorption site from the colon to the small intestine. This may affect future interventions concerning the health benefits of citrus flavonoids.

Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice

Flavonoids have been identified as the antidiabetic components in a number of traditional ethnic remedies. However, the mechanisms whereby these compounds exert their hypoglycemic and hypolipidemic action in type-2 diabetes have rarely been investigated. Therefore, this study investigated the effect of the flavonoids hesperidin and naringin on glucose and lipid regulation in C57BL/KsJ-db/db mice. Hesperidin and naringin both significantly increased the glucokinase mRNA level, while naringin also lowered the mRNA expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver. In addition, the hepatic glucose transporter 2 protein expression was significantly reduced, while the expression of adipocyte glucose transporter 4 and hepatic and adipocyte peroxisome proliferator-activated receptor γ were elevated in the hesperidin and naringin groups when compared with the control group. Furthermore, hesperidin and naringin effectively lowered the plasma free fatty acid and plasma and hepatic triglyceride levels, and simultaneously reduced the hepatic fatty acid oxidation and carnitine palmitoyl transferase activity. These changes were seemingly attributable to a suppression of the hepatic fatty acid synthase, glucose-6-phosphate dehydrogenase, and phosphatidate phosphohydrolase activities and an increase in the fecal triglycerides. The two flavonoids also led to a decrease in the plasma and hepatic cholesterol levels that may have been partly due to the decreased hepatic 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase and acyl CoA: cholesterol acyltransferase (ACAT) activities and increased fecal cholesterol. Consequently, the current results suggest that hesperidin and naringin are beneficial for improving hyperlipidemia and hyperglycemia in type-2 diabetic animals by partly regulating the fatty acid and cholesterol metabolism and affecting the gene expression of glucose-regulating enzymes.