The aim of this study was to investigate the protective effect of naringenin on oxidative stress, on proinflammatory cytokines like TGF-beta1, IL-1beta and on programmed cell death in the testicular damage resulting from streptozotocin (STZ) induced diabetes in rats. Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg), and the rats were treated with naringenin (5 mg/kg and 10 mg/kg) administered once a day orally for 10 weeks, starting 3 days after the STZ injection. At the end of the study, all animals were sacrificed. Testis tissue and blood samples were collected for the assessment of sperm parameters, and for biochemical and histopathological analysis. Naringenin treatment significantly decreased the levels of elevated tissue TBARS (thio-barbituric acid) and increased the superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) enzyme activities in the testis tissues. The naringenin-treated rats in the diabetic group showed an improved histological appearance, sperm parameters, and serum testosterone levels, along with a decrement of terminal dUTP nick end-labeling (TUNEL) detected program cell death and a reduced over expression of TGF-beta1, IL-1beta in Sertoli cells and Leydig cells. These results suggest that naringenin is a food supplement potentially beneficial in reducing testicular damage in diabetic rats by decreasing the oxidative stress related to programmed cell death.
- MeSH
- Estrogen Antagonists administration & dosage pharmacology MeSH
- Apoptosis drug effects MeSH
- Diabetes Mellitus, Experimental * drug therapy blood MeSH
- Flavanones * administration & dosage pharmacology MeSH
- Immunohistochemistry MeSH
- Interleukin-1beta MeSH
- Sperm Motility drug effects MeSH
- Oxidative Stress drug effects MeSH
- Sperm Count statistics & numerical data MeSH
- Rats, Wistar MeSH
- Microscopy, Scanning Tunneling MeSH
- Statistics as Topic MeSH
- Case-Control Studies MeSH
- Testis * enzymology immunology pathology MeSH
- Testosterone blood MeSH
- Transforming Growth Factor beta1 MeSH
- Germ Cells drug effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
Phytochemicals are widely present in fruits, vegetables and other plants and have great health benefits owing to their antioxidant properties. They are naturally found in the aquatic environment as well as discharged from sewage treatment plants after their large consumption. Little is known about their impact on fish; particularly in light of their interactions with pharmaceuticals. Therefore, this study was designed to determine the effects of diosmin, naringenin, quercetin and idole-3-carbinol on CYP1A-dependent 7-ethoxyresorufin-O-deethylase (EROD) activity on rainbow trout hepatic microsomes in the presence of two pharmaceuticals: clotrimazole and dexamethasone. The interactions between the phytochemicals and pharmaceuticals used in this study were determined using a combination index. Hepatic microsomes were exposed to two concentrations (1-or 50 μM) of phytochemicals and pharmaceuticals separately and in combinations. Singly, clotrimazole inhibited EROD activity 40% and 90% of control, while dexamethasone did not. Naringenin and diosmin inhibited EROD activity alone up to 90% and 55% respectively, but activities were further inhibited in the presence of either pharmaceutical. The preliminary study of combinations of clotrimazole with phytochemicals primarily showed synergistic effects. While EROD activity was not inhibited in the presence of quercetin or indole-3-carbinol, significant and synergistic inhibition was detected when either of these was combined with clotrimazole or dexamethasone.
- MeSH
- Cytochrome P-450 CYP1A1 chemistry metabolism MeSH
- Dexamethasone chemistry pharmacology MeSH
- Diosmin chemistry pharmacology MeSH
- Flavanones chemistry pharmacology MeSH
- Indoles chemistry pharmacology MeSH
- Enzyme Inhibitors chemistry pharmacology MeSH
- Microsomes, Liver drug effects enzymology MeSH
- Liver drug effects enzymology MeSH
- Kinetics MeSH
- Clotrimazole chemistry pharmacology MeSH
- Oncorhynchus mykiss metabolism MeSH
- Quercetin chemistry pharmacology MeSH
- Fish Proteins chemistry metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
Flavonoids are known to have effects on cytochrome P450 enzymatic activity. However, little effort has been made to examine species differences and the relevance of studies on mammalian and fish microsomes so that extrapolations can be made to humans. Therefore, the effects of several naturally occurring flavonoids on the activity of CYP3A-dependent 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD) were evaluated in human, pig, mouse, and juvenile rainbow trout sources of hepatic microsomes. Each was exposed to three concentrations (1, 10, and 100μM) of diosmin, naringin, and naringenin. Naringenin competitively inhibited BFCOD activity (Ki values were 24.6μM in human, 15.6μM in pig, and 19.6μM in mouse microsomes). In fish, BFCOD activity was inhibited in a noncompetitive manner (Ki=7μM). Neither diosmin nor naringenin affected BFCOD activity in hepatic microsomes from the studied model organisms. These results suggest that dietary flavonoids potentially inhibit the metabolism of clinical drugs.
- MeSH
- Citrus chemistry MeSH
- Cytochrome P-450 CYP3A genetics metabolism MeSH
- Diosmin pharmacology MeSH
- Species Specificity MeSH
- Gene Expression MeSH
- Flavanones pharmacology MeSH
- Hydrolysis MeSH
- Enzyme Inhibitors pharmacology MeSH
- Microsomes, Liver drug effects enzymology MeSH
- Liver drug effects enzymology MeSH
- Kinetics MeSH
- Coumarins metabolism MeSH
- Humans MeSH
- Mice, Inbred ICR MeSH
- Mice MeSH
- Oncorhynchus mykiss MeSH
- Swine MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Luteolin and naringenin are flavonoids found in various foods/beverages and present in certain dietary supplements. After a high intake of these flavonoids, their sulfate and glucuronide conjugates reach micromolar concentrations in the bloodstream. Some pharmacokinetic interactions of luteolin and naringenin have been investigated in previous studies; however, only limited data are available in regard to their metabolites. In this study, we aimed to investigate the interactions of the sulfate and glucuronic acid conjugates of luteolin and naringenin with human serum albumin, cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes, and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters. Our main findings are as follows: (1) Sulfate conjugates formed more stable complexes with albumin than the parent flavonoids. (2) Luteolin and naringenin conjugates showed no or only weak inhibitory action on the CYP enzymes examined. (3) Certain conjugates of luteolin and naringenin are potent inhibitors of OATP1B1 and/or OATP2B1 enzymes. (4) Conjugated metabolites of luteolin and naringenin may play an important role in the pharmacokinetic interactions of these flavonoids.
- MeSH
- Cytochrome P-450 CYP3A * metabolism MeSH
- Cytochrome P-450 CYP2C19 metabolism MeSH
- Cytochrome P-450 CYP2C9 metabolism MeSH
- Flavonoids pharmacology MeSH
- Glucuronides MeSH
- Humans MeSH
- Serum Albumin, Human metabolism MeSH
- Luteolin pharmacology MeSH
- Organic Anion Transporters * metabolism MeSH
- Sulfates metabolism MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The aim of the present study was to evaluate in vitro effects of dietary phytochemicals naringenin, quercetin, and sesamin on the activities of ethoxy- (EROD; CYP1A) and benzyloxy- (BROD; CYP3A) resorufin O-dealkylases after the exposure to the cocktail of persistent organic pollutants (POPs). CD-1 mice were exposed from weaning, through gestation and lactation to a defined mixture of POPs. Hepatic microsomes were prepared from their female offspring at postnatal day 42. Hepatic EROD and BROD activity were evaluated in the presence of quercetin, naringenin, and sesamin at nine concentrations from 5 to 100000 nM. EROD activity was strongly inhibited by quercetin withKivalues from 1.7 to 2.6 μM. BROD activity was inhibited by quercetin withKivalues from 64.9 to 75.3 μM and naringenin withKivalues from 39.3 to 45.8 μM. The IC50andKivalues did not differ between the groups of mice with different levels of POPs exposure in any of the experimental sets. Sesamin did not inhibit either EROD or BROD. We concluded that the interactions of quercetin and naringenin with CYP1A and CYP3A in mice liver were not affected by the levels of POPs exposure.
- MeSH
- Dioxoles pharmacology MeSH
- Flavanones pharmacology MeSH
- Microsomes, Liver enzymology pathology MeSH
- Air Pollutants toxicity MeSH
- Lignans pharmacology MeSH
- Maternal Exposure adverse effects MeSH
- Mice MeSH
- Quercetin pharmacology MeSH
- Cytochrome P450 Family 1 metabolism MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Pregnancy MeSH
- Prenatal Exposure Delayed Effects chemically induced enzymology pathology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
As a common complication of diabetes mellitus (DM), diabetic cardiomyopathy (DCM) is considered to be one of the major causes of mortality and morbidity. The therapeutic effects of naringenin have been verified in the treatment of various human diseases. However, the application of naringenin in the treatment of DCM still has not been reported. In this study, human AC16 cardiac cells were treated with normal d-glucose and high d-glucose (HG). After transfection with miR-30d-5p inhibitor, Cell Counting Kit-8 (CCK-8) method was used to measure cell viability. Hoechst 33258 staining was performed to observe the morphological changes of nucleus. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the activity of caspase-3. Cell apoptosis was detected by Annexin V-FITC/propidium iodide (PI) staining. Levels of light chain 3 (LC3) including LC3-I and LC3-II as well as nucleoporin p62 (P62) were detected by Western blot. We found that Naringenin treatment increased the reduced cell variability caused by HG treatment. Naringenin also increased expression level of miR-30d-5p in human AC16 cardiac cells after HG treatment. Treatment with miR-30d-5p inhibitor reduced the effect of miR-30d-5p in increasing cell variability and reducing cell apoptosis. Naringenin treatment reduced the increased levels of LC-I, LC-II and P62, but miR-30d-5p inhibitor reduced those changes. Therefore we concluded that naringenin could alleviate HG-induced injuries through the upregulation of microRNA-30d-5p level in human AC16 cardiac cells.
- MeSH
- Annexins analysis MeSH
- Apoptosis drug effects MeSH
- Diabetic Cardiomyopathies * drug therapy chemically induced MeSH
- Flavanones administration & dosage pharmacology MeSH
- Myocytes, Cardiac drug effects MeSH
- Cardiotonic Agents MeSH
- Caspase 3 analysis metabolism drug effects MeSH
- Cells, Cultured drug effects MeSH
- MicroRNAs analysis drug effects MeSH
Nonhealed wounds are one of the most dangerous side effects of type-2 diabetes, which is linked to a high frequency of bacterial infections around the globe that eventually results in amputation of limbs. The present investigation aimed to explore the drug-loaded (naringenin) hydrogel system for chronic wound healing. The hydrogel membranes comprising Na-alginate with F-127 and poly(vinyl alcohol) were developed to treat chronic wounds using the quality-by-design (QbD) approach. The optimized formulation was tested for various parameters, such as swelling, gel fraction, water vapor transition rate (WVTR), etc. In vitro evaluation indicated that a drug-loaded hydrogel displayed better tissue adhesiveness and can release drugs for a prolonged duration of 12 h. Scratch assay performed on L929 cell lines demonstrated good cell migration. The diabetic wound healing potential of the hydrogel membrane was assessed in streptozotocin-induced male Wistar rats (50 mg/kg). Higher rates of wound closure, re-epithelialization, and accumulation of collagen were seen in in vivo experiments. Histopathologic investigation correspondingly implied that the drug-loaded hydrogel could enhance dermal wound repair. The improved antimicrobial and antioxidant properties with expedited healing indicated that the drug-loaded hydrogel is a perfect dressing for chronic wounds.
- Publication type
- Journal Article MeSH
The root exudates of alfalfa (Medicago sativa) and mungbean (Vigna radiata) induced the Tsr (thick and short roots) factor production in Rhizobium meliloti. The factor caused a 30-40% reduction of root length in alfalfa seedlings. Pea root exudate had no Tsr induction activity. The flavonoid naringenin could replace the roots in inducing Tsr production. Naringenin-induced Tsr factor caused 70% shortening of main roots. The Tsr inducing property of naringenin was specific since quercetin and syringaldehyde had no such effect.
- MeSH
- Bacterial Proteins biosynthesis MeSH
- Flavanones * MeSH
- Flavonoids pharmacology MeSH
- Medicago sativa metabolism microbiology MeSH
- Membrane Proteins biosynthesis MeSH
- Sinorhizobium meliloti drug effects growth & development metabolism MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
This study shows the effects of spices, and their phenolic and flavonoid compounds, on prostate cell lines (PNT1A, 22RV1 and PC3). The results of an MTT assay on extracts from eight spices revealed the strongest inhibitory effects were from black pepper and caraway seed extracts. The strongest inhibitory effect on prostatic cells was observed after the application of extracts of spices in concentration of 12.5 mg·mL-1. An LC/MS analysis identified that the most abundant phenolic and flavonoid compounds in black pepper are 3,4-dihydroxybenzaldehyde and naringenin chalcone, while the most abundant phenolic and flavonoid compounds in caraway seeds are neochlorogenic acid and apigenin. Using an MTT assay for the phenolic and flavonoid compounds from spices, we identified the IC50 value of ~1 mmol·L-1 PNT1A. The scratch test demonstrated that the most potent inhibitory effect on PNT1A, 22RV1 and PC3 cells is from the naringenin chalcone contained in black pepper. From the spectrum of compounds assessed, the naringenin chalcone contained in black pepper was identified as the most potent inhibitor of the growth of prostate cells.
- MeSH
- Anticarcinogenic Agents chemistry pharmacology MeSH
- Cell Line MeSH
- Chromatography, Liquid MeSH
- Phenols chemistry pharmacology MeSH
- Flavonoids chemistry pharmacology MeSH
- Mass Spectrometry MeSH
- Wound Healing drug effects MeSH
- Spices analysis MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation drug effects MeSH
- Prostate MeSH
- Plant Extracts chemistry pharmacology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
Nowadays, much research attention is focused on underutilized berry crops due to the high antioxidant activity of fruits. Black crowberry (Empetrum nigrum L.) represents an important source of flavonols (quercetin, rutin, myricetin, naringenin, naringin, morin, and kaempferol) and anthocyanins. The fruit components could be utilised as natural colourants or as a part of functional foods and, because of the high antioxidant activity, the berries of black crowberry can be used in the treatment of diseases accompanied with inflammation, or as an effective antibacterial and antifungal remedy. Moreover, the reduction of lipid accumulation and total cholesterol as well as an improvement of postprandial hyperglycaemia have been proven. This review summarizes for the first time the main antioxidants (flavonoids) of black crowberry fruits, with a focus on their health promoting activity.
- MeSH
- Ericaceae chemistry MeSH
- Flavonoids pharmacology MeSH
- Humans MeSH
- Fruit chemistry MeSH
- Health Promotion MeSH
- Plant Extracts pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
