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Dan Liu, Jie Wu, Hongbo Xie, Mingyi Liu, Isaiah Takau, Hong Zhang, Yuqing Xiong, Chunhua Xia
Hesperetin (HET) and naringenin (NGR) are flavanones found in citrus (oranges and grapefruit) and Aurantii Fructus Immaturus. The present study aims to investigate the inhibition potential of HET and NGR derivatives towards one of the most important phase II drug-metabolizing enzymes-uridine diphosphate (UDP)-glucuronosyltransferases (UGTs). We used trifluoperazine as a probe substrate to test UGT1A4 activity, and recombinant UGT-catalyzed 4-methylumbelliferone glucuronidation was used as a probe reaction for other UGT isoforms...
2016: Biological & Pharmaceutical Bulletin
Adrian Oo, Pouya Hassandarvish, Sek Peng Chin, Vannajan Sanghiran Lee, Sazaly Abu Bakar, Keivan Zandi
BACKGROUND: The re-emerging, Aedes spp. transmitted Chikungunya virus (CHIKV) has recently caused large outbreaks in a wide geographical distribution of the world including countries in Europe and America. Though fatalities associated with this self-remitting disease were rarely reported, quality of patients' lives have been severely diminished by polyarthralgia recurrence. Neither effective antiviral treatment nor vaccines are available for CHIKV. Our previous in vitro screening showed that hesperetin, a bioflavonoid exhibits inhibitory effect on the virus intracellular replication...
2016: PeerJ
Kalist Shagirtha, Nazima Bashir, Selvaraj MiltonPrabu
The present study was designed to investigate the neuroprotective effect of hesperetin (Hp) against cadmium (Cd)-induced neurotoxicity in rats. Cadmium (3 mg/kg body weight (b.w.), subcutaneous) administration for 3 weeks demonstrated neurotoxicity in rats by the decreased activity of acetylcholinesterase in the brain. The oxidative stress markers (thiobarbituric acid reactive substances and protein carbonyls) were significantly increased with decreased enzymatic (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase) and non-enzymatic antioxidants (reduced glutathione, total sulphydryl groups and vitamin C)...
November 1, 2016: Toxicology and Industrial Health
Noriko Hiraishi, Takahiro Maruno, Naoya Tochio, Ryohei Sono, Masayuki Otsuki, Tsutomu Takatsuka, Junji Tagami, Yuji Kobayashi
OBJECTIVE: Dentin collagen can be modified by some plant-derived flavonoids to improve properties of dentin organic matrix. Hesperidin (HPN), a hesperetin-7-O-rutinoside flavonoid, has a potential of dentin modification for being based on evidence that a treatment with HPN may resist collagenase degradation and arrest demineralization of human dentin. In this study, biophysical and molecular-level information on the interaction of HPN and collagen was investigated. METHODS: HPN is extracted from citrus fruits...
October 19, 2016: Dental Materials: Official Publication of the Academy of Dental Materials
Gema Pereira-Caro, Begoña Fernández-Quirós, Iziar A Ludwig, Inmaculada Pradas, Alan Crozier, José Manuel Moreno-Rojas
PURPOSE: Orange juice (OJ) flavanones undergo limited absorption in the upper gastrointestinal tract and reach the colon where they are transformed by the microbiota prior to absorption. This study investigated the ability of two probiotic bacteria, Bifidobacterium longum R0175 and Lactobacillus rhamnosus subsp. Rhamnosus NCTC 10302 to catabolise OJ flavanones. METHODS: The bacteria were incubated with hesperetin-7-O-rutinoside, naringenin-7-O-rutinoside, hesperetin and naringenin, and the culture medium and intracellular cell extracts were collected at intervals over a 48 h of incubation period...
October 8, 2016: European Journal of Nutrition
Marta Mendel, Magdalena Chłopecka, Natalia Dziekan, Wojciech Karlik
Citrus flavonoids are acknowledged for numerous pharmacological activities, including the myorelaxant effect on various smooth muscles. However, there is no data on their effect on jejunum contractility. Therefore, the aim of the study at hand was to evaluate the impact of hesperetin and diosmetin along with their glycosides on the motoric activity of intestine and to verify the possible mechanism of hesperetin-induced effect. The experiments were performed on rat isolated jejunum strips and were conducted under isometric conditions...
October 6, 2016: European Journal of Pharmacology
Xueting Bai, Peixuan Yang, Qiaoling Zhou, Bozhi Cai, Manon Buist-Homan, He Cheng, Jiyang Jiang, Daifei Shen, Lijun Li, Xiajiong Luo, Klaas Nico Faber, Han Moshage, Ganggang Shi
BACKGROUND AND PURPOSE: Liver diseases are mostly accompanied by inflammation and hepatocyte death. Therapeutic approaches targeting both hepatocyte injury and inflammation are not available. Natural compounds are considered as potential treatment for inflammatory liver diseases. Hesperetin, a flavonoid component of citrus fruits has been reported to have anti-inflammatory properties. The aim of this study was to evaluate the cytoprotective and anti-inflammatory properties of hesperetin both in vitro and in models of fulminant hepatitis...
October 7, 2016: British Journal of Pharmacology
Huan Wang, Hong-Fei Wang, Hao Zhang, Chen Wang, Yu-Fang Chen, Rong Ma, Ji-Zhou Xiang, Xin-Ling Du, Qiang Tang
AIM: Voltage-gated sodium channels composed of a pore-forming α subunit and auxiliary β subunits are responsible for the upstroke of the action potential in cardiac myocytes. The pore-forming subunit of the cardiac sodium channel Nav1.5, which is encoded by SCN5A, is the main ion channel that conducts the voltage-gated cardiac sodium current (INa) in cardiac cells. The current study sought to investigate the inhibitory effects of hesperetin on human cardiac Nav1.5 channels stably expressed in human embryonic kidney 293 (HEK 293) cells and on the voltage-gated cardiac sodium current (INa) in human atrial myocytes...
December 2016: Acta Pharmacologica Sinica
André Lucio Franceschini Sarria, Adriana Ferreira Lopes Vilela, Bárbara Mammana Frugeri, João Batista Fernandes, Rose Maria Carlos, Maria Fátima das Graças Fernandes da Silva, Quezia Bezerra Cass, Carmen Lúcia Cardoso
Metal chelates strongly influence the nature and magnitude of pharmacological activities in flavonoids. In recent years, studies have shown that a promising class of flavanone-metal ion complexes can act as selective cholinesterase inhibitors (ChEIs), which has led our group to synthesize a new series of flavanone derivatives (hesperidin, hesperetin, naringin, and naringenin) complexed to either copper (II) or zinc (II) and to evaluate their potential use as selective ChEIs. Most of the synthesized complexes exhibited greater inhibitory activity against acetylcholinesterase (AChE) than against butyrylcholinesterase (BChE)...
September 17, 2016: Journal of Inorganic Biochemistry
Marko Miler, Jasmina Živanović, Vladimir Ajdžanović, Zorana Oreščanin-Dušić, Dragan Milenković, Aleksandra Konić-Ristić, Duško Blagojević, Verica Milošević, Branka Šošić-Jurjević
This study aimed to investigate effects of citrus flavanones naringenin (NAR) and hesperetin (HES) on liver antioxidant status and membrane phospholipid composition in 24-month-old rats. NAR and HES (15mg/kg) were administrated orally to male Wistar rats, once per day, for 4weeks. Control group received either vehicle (sunflower oil) or remained intact. The results showed decreased (p<0.05) activity of antioxidant enzymes (AOE), specifically catalase (CAT), superoxide dismutase (SOD) 1 and glutathione reductase (GR) in the liver of intact control old-aged rats in comparison to young intact controls...
November 2016: Experimental Gerontology
Ruonan Chen, Lan Li, Chenlin Shen, Cheng Huang, Taotao Ma, Xiaoming Meng, Zhengyue Qian, Yangyang Li, Jun Li
1. Hesperetin (HDND) possesses extensive bioactivities, however, its poor solubility and low bioavailability limit its application. HDND-7, a derivative of HDND, has better solubility and high bioavailability. In this study, we investigated the intestinal absorption mechanisms of HDND-7. 2. MDCK cells were used to examine the transport mechanisms of HDND-7 in vitro, and a rat in situ intestinal perfusion model was used to characterize the absorption of HDND-7. The concentration of HDND-7 was determined by HPLC...
August 18, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Luan Luong Chu, Ramesh Prasad Pandey, Narae Jung, Hye Jin Jung, Eun-Hee Kim, Jae Kyung Sohng
BACKGROUND: Cytochrome P450 monooxygenase constitutes a significant group of oxidative enzymes that can introduce an oxygen atom in a high regio- and stereo-selectivity mode. We used the Bacillus megaterium cytochrome P450 BM3 (CYP450 BM3) and its variants namely mutant 13 (M13) and mutant 15 (M15) for the hydroxylation of diverse class of flavonoids. RESULTS: Among 20 flavonoids, maximum seven flavonoids were hydroxylated by the variants while none of these molecules were accepted by CYP450 BM3 in in vitro reaction...
2016: Microbial Cell Factories
Katrin Sak, Kristi Kasemaa, Hele Everaus
Despite numerous studies chronic lymphocytic leukemia (CLL) still remains an incurable disease. Therefore, all new compounds and novel strategies which are able to eradicate CLL cells should be considered as valuable clues for a potential future remedy against this malignancy. In the present study, the cytotoxic profiles of natural flavonoids were described in two human CLL cell lines, HG-3 and EHEB, indicating the flavone luteolin as the most potent flavonoid with half-maximal inhibitory constants (IC50) of 37 μM and 26 μM, respectively...
September 14, 2016: Food & Function
Julian K Aschoff, Ken M Riedl, Jessica L Cooperstone, Josef Högel, Anja Bosy-Westphal, Steven J Schwartz, Reinhold Carle, Ralf M Schweiggert
SCOPE: Orange juice contains flavanones including hesperidin and narirutin, albeit at lower concentrations as compared to orange fruit. Therefore, we compared bioavailability and colonic catabolism of flavanones from orange juice to a 2.4-fold higher dose from fresh oranges. METHODS AND RESULTS: Following a randomized two-way cross-over design, 12 healthy subjects consumed a test meal comprising either fresh oranges or pasteurized orange juice, delivering 1774 and 751 μmol of total Citrus flavanones, respectively...
August 4, 2016: Molecular Nutrition & Food Research
Irena Baranowska, Judyta Hejniak, Sylwia Magiera
A quick and sensitive RP-UHPLC-ESI-MS/MS method for the separation of flavanone, naringenin and hesperetin enantiomers was developed. The separation of analytes was performed using a Chiralpak AD-3R column, and methanol was used as the mobile phase. Detection was carried out using a triple quadrupole tandem mass spectrometer with an electrospray ionisation source. Positive ionisation and multiple reaction monitoring (MRM) were used. The developed method showed satisfactory linearity with determination coefficients greater than 0...
October 1, 2016: Talanta
Bhavya Balan Chandrika, Mathew Steephan, T R Santhosh Kumar, A Sabu, M Haridas
AIM: Aberrant human epidermal growth factor receptor-2 (HER2) expression and constitutive mutant activation of its tyrosine kinase domain account for tumor aggression and therapy resistance in many types of cancers with major share in breast cancer cases. HER2 specific treatment modalities still face challenges owing to the side effects and acquired resistance of available therapeutics. Recently, the anti-proliferative and pro-apoptotic potential of phytochemicals, especially of flavonoids have become increasingly appreciated as powerful chemo preventive agents...
September 1, 2016: Life Sciences
Huan Wang, Hong-Fei Wang, Chen Wang, Yu-Fang Chen, Rong Ma, Ji-Zhou Xiang, Xin-Ling Du, Qiang Tang
In the present study, the inhibitory effects of hesperetin (HSP) on human cardiac Kv1.5 channels expressed in HEK 293 cells and the ultra-rapid delayed rectifier K(+) current (Ikur) in human atrial myocytes were examined by using the whole-cell configuration of the patch-clamp techniques. We found that hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition (IC50) of 23.15 μΜ with a Hill coefficient of 0.89. The current was maximally diminished about 71...
October 15, 2016: European Journal of Pharmacology
Orsolya Roza, Ana Martins, Judit Hohmann, Wan-Chun Lai, Jacobus Eloff, Fang-Rong Chang, Dezső Csupor
The present paper reports the chemical analysis of the methanolic extracts of fermented and non-fermented Cyclopia genistoides herbs and an investigation of the xanthine oxidase inhibitory activity of the isolated constituents. Chemical analysis of the leaves and stems of C. genistoides yielded the isolation and identification of two benzophenone glucosides, iriflophenone 2-O-β-glucopyranoside (1) and iriflophenone 3-C-β-glucopyranoside (2), two pterocarpans, (6aR,11aR)-(-)-2-methoxymaackiain (5) and (6aR,11aR)-(-)-maackiain (6), along with the flavanones liquiritigenin (9) and hesperetin (10), the flavone diosmetin (11), the isoflavones afrormosin (7) and formononetin (8), piceol (3), and 4-hydroxybenzaldehid (4)...
September 2016: Planta Medica
Blanca Escudero-López, Isabel Cerrillo, Ángel Gil-Izquierdo, Dámaso Hornero-Méndez, Griselda Herrero-Martín, Genoveva Berná, Sonia Medina, Federico Ferreres, Franz Martín, María-Soledad Fernández-Pachón
Previously, we reported that alcoholic fermentation enhanced flavanones and carotenoids content of orange juice. The aim of this work was to evaluate the influence of pasteurization on the qualitative and quantitative profile of bioactive compounds and the antioxidant capacity of fermented orange juice. Ascorbic acid (203 mg/L), total flavanones (647 mg/L), total carotenoids (7.07 mg/L) and provitamin A (90.06 RAEs/L) values of pasteurized orange beverage were lower than those of fermented juice. Total phenolic remained unchanged (585 mg/L) and was similar to that of original juice...
November 2016: International Journal of Food Sciences and Nutrition
Nora A Bawazeer, Hani Choudhry, Mazin A Zamzami, Wesam H Abdulaal, Bruce Middleton, Said S Moselhy
BACKGROUND: High plasma concentration of low-density lipoprotein cholesterol (LDL-c) plays a significant role in the incidence of atherosclerosis and coronary heart diseases. The aim of this study was to investigate the mechanism by which the citrus flavonoid, hesperetin, regulates the LDL receptor (LDLr) gene in the human liver using the human hepatoma cell line, HepG2. METHODS: Luciferase reporter gene assays were performed (in the absence of lipoprotein) to measure the activity of the LDLr promoter and the promoters of the sterol regulatory element binding protein (SREBP) transcription factors that control the LDLr promoter...
2016: BMC Complementary and Alternative Medicine
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