Investigation of the histopathological level of Ki-67, caspase-3 expressions of the effects of hesperidin on wound healing in the rat esophagus

Purpose: The effects of hesperidin application on the wound caused by esophageal burns were investigated in this study. Methods: Wistar albino rats were divided into three groups: Control group: only 1 mL of 0.09% NaCl was administered i.p. for 28 days; Burn group: An alkaline esophageal burn model was created with 0.2 mL of 25% NaOH orally by gavage­1 mL of 0.09% NaCl was administered i.p. for 28 days; Burn+Hesperidin group: 1 mL of 50 mL/kg of hesperidin was given i.p. for 28 days to rats after burn injury. Blood samples were collected for biochemical analysis. Esophagus samples were processed for histochemical staining and immunohistochemistry. Results: Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly increased in Burn group. Glutathione (GSH) content and histological scores of epithelialization, collagen formation, neovascularization was decreased. After hesperidin treatment, these values were significantly improved in the Burn+Hesperidin group. In the Burn group, epithelial cells and muscular layers were degenerated. Hesperidin treatment restored these pathologies in Burn+Hesperidin group. Ki-67 and caspase-3 expressions were mainly negative in control group; however, the expression was increased in the Burn group. In the Burn+Hesperidin group, Ki-67 and caspase-3 immune activities were reduced. Conclusion: Hesperidin dosage and application methods can be developed as an alternative treatment for burn healing and treatment.

Therapeutic effect of neohesperidin on TNF-α-stimulated human rheumatoid arthritis fibroblast-like synoviocytes / 中国天然药物

During the pathogensis of rheumatoid arthritis (RA), activated RA fibroblast-like synoviocytes (RA-FLSs) combines similar proliferative features as tumor and inflammatory features as osteoarthritis, which eventually leads to joint erosion. Therefore, it is imperative to research and develop new compounds, which can effectively inhibit abnormal activation of RA-FLSs and retard RA progression. Neohesperidin (Neo) is a major active component of flavonoid compounds with anti-inflammation and anti-oxidant properties. In this study, the anti-inflammation, anti-migration, anti-invasion, anti-oxidant and apoptosis-induced effects of Neo on RA-FLSs were explored to investigate the underlying mechanism. The results suggested that Neo decreased the levels of interleukin IL-1β, IL-6, IL-8, TNF-α, MMP-3, MMP-9 and MMP-13 in FLSs. Moreover, Neo blocked the activation of the MAPK signaling pathway. Furthermore, treatment with Neo induced the apoptosis of FLSs, and inhibited the migration of FLSs. It was also found that Neo reduced the accumulation of reactive oxygen species (ROS) induced by TNF-α. Taken together, our results highlighted that Neo may act as a potential and promising therapeutic drug for the management of RA.

Optimized Chitosan-Coated Gliadin Nanoparticles Improved the Hesperidin Cytotoxicity over Tumor Cells

Abstract Hesperidin is a natural compound which is found in citric fruits and presents antitumor and antimicrobial activities. However, the in vivo efficacy of Hesperidin is reduced due to its low oral bioavailability. Protein-based nanoparticles have been applied to improve biological parameters of drugs and natural compounds. Gliadin is a monomeric protein present in wheat. In this study, gliadin-based nanoparticles containing hesperidin were obtained by desolvation technique and a Taguchi orthogonal array design was employed to optimize the formulation. The independent variables were set as concentration of CaCl2 (0.5; 1 or 2%) and stabilizing agent (Pluronic F68, Tween 80 or sodium caseinate). The dependent variables consisted of mean diameter, polydispersity index, zeta potential, and encapsulation efficiency. The results showed significant effects on the dependent variables when 1% CaCl2 and Pluronic F68 were used. The optimized formulation was coated with chitosan to increase the physical stability of the nanoparticles. The final nanoparticles presented a mean diameter of 321 nm and polydispersity index of 0.217, and spherical shape. After coating, the Zeta potential was +21 mV, and the encapsulation efficiency was 73 %. The in vitro release assay showed that about 98% of the drug was released from the nanoparticles after 48 h. Moreover, the nanoparticles reduced hesperidin cytotoxicity on healthy cells (Vero cells) and improved the cytotoxicity on tumor cells (HeLa, PC-3 and Caco-2 cells). Results showed that the chitosan-coated gliadin nanoparticles are potential carriers for hesperidin delivery for cancer treatment.

Principales plantas medicinales disponibles en Guatemala con actividad contra virus respiratorios que infectan al ser humano ­ Revisión narrativa / Main medicinal plants available in Guatemala with activity against respiratory virus that infects the human being ­ Narrative review

Las infecciones respiratorias constituyen una importante causa de morbilidad y mortalidad a nivel mundial, incrementándose su relevancia ante la reciente infección por SARS-CoV-2, causante de la pandemia de COVID-19. Las opciones terapéuticas para esta infección respiratoria son escasas y sin eficacia comprobada. El objetivo de esta revisión fue buscar la información sobre plantas con actividad antiviral o viricida publicada en los últimos 10 años, en las bases de datos de Google Scholar, Scopus y PubMed. La búsqueda priorizó aquellas especies disponibles en Guatemala, la cual se complementó con la búsqueda de moléculas con actividad antiviral para finalmente postular aquellas que puedan prevenir la infección o aminorar la patogénesis del SARS-CoV-2. Se detectaron más de 170 especies con actividad antiviral y se organizó la información por país o región y tipo de actividad antiviral contra virus específicos. De las especies de mayor disponibilidad en Guatemala se seleccionaron 20. La revisión culmina con 15 artículos que proponen plantas o moléculas con potencial actividad específica en el manejo de la pandemia por SARS-CoV-2. Se concluye que existen especies vegetales (Curcuma longa, Echinacea purpurea, Psidium guajava, Allium sativum, Salvia officinalis y Eucalyptus globulus) y fitocompuestos vegetales (hesperidina, rutina, diosmina, apiina, aloe-emodina, piperina, capsaicina, curcumina, oleuropeina, rhamnetina y gallato de epicatequina) que podrían contribuir al manejo de la enfermedad. Se insta a académicos y autoridades a poner más atención a estas opciones terapéuticas que nos ofrece la naturaleza y que podrían contribuir a aliviar el colapso de los sistemas de salud prevalentes.

Respiratory infections are an important cause of morbidity and mortality worldwide, increasing their relevance by the recent SARS-CoV-2 infection causing the COVID-19 pandemic. Therapeutic options for this respiratory infection are scarce and without proven effectiveness. The objective of this review was the search for information on plants with antiviral or viricidal activity published in the last 10 years in the Google Scholar, Scopus, and PubMed databases. The search prioritized those species available in Guatemala, was completed with the search of molecules with potential to prevent infection or reduce the activity of SARS-CoV-2 infection. More than 170 species with antiviral activity were detected and the information organized in surveys by country or region, activity against specific viruses and antiviral information on the 20 most commonly available species in the country. It is complemented with a summary of 15 articles that proposed plants or molecules with potential specific activity in the management of the SARS-CoV-2 pandemic. It is concluded there are plant species (Curcuma longa, Echinacea purpurea, Psidium guajava, Allium sativum, Salvia officinalis and Eucalyptus globulus) and phytocompounds isolated from these species (hesperidin, rutin, diosmin, apiine, aloe-emodin, piperine, capsaicin, curcumin, oleuropein and epicatechin gallate) that could contribute to the management of the disease. Academics and authorities are urged to pay more attention to these therapeutic options that nature offer to us and could contribute to alleviate the collapse of the prevailing health systems in the country.

Estudo comparativo da excreção de flavonoides entre indivíduos eutróficos e obesos, após a ingestão de sucos de laranja, cv. Pera e cv. Moro / Comparative study of excretion of flavonoids among eutrophic and obese individuals, after ingestion of orange juice, cv. Pera and cv Moro

As laranjas e seus derivados, principalmente os sucos, possuem compostos bioativos, tais como os flavonoides, entre eles as flavanonas hesperidina e narirutina, que podem estar relacionados à promoção e benefícios à saúde. A absorção e metabolização de flavonoides podem ser afetadas por diversos fatores como a microbiota e fatores antropométricos, o que pode afetar a sua bioatividade. Assim, o objetivo deste estudo foi comparar o metabolismo e excreção dos flavonoides entre indivíduos eutróficos e obesos após a ingestão de sucos de laranja pasteurizado obtidos das cvs. Pera e Moro. Em um estudo cross-over randomizado 20 voluntárias eutróficas e 10 voluntárias obesas, com idade entre 19 e 40 anos, consumiram em dose única 600 mL de cada suco, que contém as flavanonas narirutina e hesperidina, além das antocianinas no suco Moro. Os metabólitos de flavanonas e de antocianinas foram identificados e quantificados em urina coletada em diferentes períodos de tempo durante 24 horas. Não foi observada diferença significativa na permeabilidade intestinal entre os grupos. Foram detectados e identificados 8 metabólitos de fase II da hesperitina e naringenina, principalmente mono e diglicuronidados e sulfatos, além de três ácidos fenólicos catabólitos de flavanonas formados pela microbiota intestinal, entre elas o ácido hipúrico, ácido protocatecuico e ácido 3-(3-hidroxifenil)-3-hidroxipropiônico. Os ácidos fenólicos foram os metabólitos majoritários recuperados na urina, principalmente o ácido hipúrico. Ainda, os metabólitos de fase II apresentaram maior excreção entre o período de 4-8h e 8-12h (13 a 27% do total de metabólitos excretados). Não foi observada diferença significante (p<0,05) no total de metabólitos de naringenina e hesperitina excretados na urina durante o período de 24 h entre os dois grupos e para os sucos de laranja, nem para o total de metabólitos, provavelmente devido à grande variabilidade interindividual na excreção. Assim, não foi observada diferença entre a metabolização de flavanonas de laranja entre os eutróficos e obesos e nenhuma correlação com os parâmetros antropométricos avaliados

Oranges and orange juices contain bioactive compounds, such as flavonoids, mainly the flavanones hesperidin and narirutin, which may be related to the promotion and health benefits. The absorption and metabolization of flavonoids can be affected by several factors such as the gut microbiota and anthropometric parameters, which may affect its bioactivity. Thus, the aim of this study was to compare the metabolism and excretion of flavonoids among eutrophic and obese people after ingestion of two pasteurized orange juice obtained from cvs. Pera and Moro. In a randomized cross-over study 20 eutrophic volunteers and 10 obese volunteers, aged 19-40 years, consumed a single dose of 600 mL of each juice. The metabolites of flavanones and anthocyanins were identified and quantified in urine collected at different time points for 24 hours. No significant difference in intestinal permeability was observed between groups. Eight Phase II metabolites of hesperitin and naringenin, mainly mono and diglycerides and sulfates, and three phenolic catabolites of flavanones formed by the gut microbiota were detected and identified, among them hippuric acid, protocatecuic acid and 3- (3-hydroxyphenyl) ) -3-hydroxypropionic acid. Phenolic acids were the major metabolites recovered in urine, mainly hippuric acid. Furthermore, phase II metabolites had greater excretion between the period of 4-8h and 8-12h (13-27% of total metabolites excreted). No significant difference (p <0.05) was observed in the total of naringenin and hesperitin metabolites excreted in the urine during the 24 h period between the two groups, probably due to interindividual variability in excretion. Thus, no difference was observed on metabolism of flavanones between the eutrophic and obese and no correlation was observed with the anthropometric parameters evaluated

Hesperetin derivative-12 (HDND-12) regulates macrophage polarization by modulating JAK2/STAT3 signaling pathway / 中国天然药物

Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin (HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12 (HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1 (Arg-1), interleukin-10 (IL-10), transforming growth factor β (TGF-β) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase (iNOS) was down-regulated in LPS- and IFN-γ-treated (M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490 (inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.

Benefits of hesperidin in central nervous system disorders: a review / 대한해부학회지

Hesperidin inhibits the epithelial to mesenchymal transition induced by transforming growth factor-ß1 in A549 cells through Smad signaling in the cytoplasm

Hesperidin, a natural compound, suppresses the epithelial-to-mesenchymal transition through the TGF-ß1/Smad signaling pathway. However, studies on the detailed effects and mechanisms of hesperidin are rare. The present study showed that, for A549 alveolar epithelial cells, the anti-proliferative effects of hesperidin occurred in a dose-dependent manner, with an IC50= 216.8 µM at 48 h. TGF-ß1 was used to activate the Smad signaling pathway and induce the epithelial to mesenchymal transition in cells. Treatment with hesperidin or SB431542 was used for antagonism of Smad pathway activation. Hesperidin inhibited the increase in ɑ-SMA and Col1ɑ-1 and the decrease in E-cadherin in a dose-dependent manner from concentration of 20 µM to 60 µM, as assessed by both ELISA and Western blotting assays; however, there was no significant effect on cellular morphological alterations. Moreover, the Western blotting assay showed that, in the cytoplasm, hesperidin and SB431542 had no significant effect on the protein expression of Smad 2, 3, 4, or 7 as well as 2/3. However, 60 µM hesperidin and SB431542 significantly decreased p-Smad2/3 protein expression. From the above results, it is concluded that hesperidin can partly inhibit the epithelial to mesenchymal transition in human alveolar epithelial cells; the effect accounts for the blockage of the phosphorylation of Smad2/3 in the cytoplasm rather than a change in Smad protein production in the cytoplasm

Sepsis-induced acute kidney injury: kidney protection effects by antioxidants / Lesión renal aguda inducida por sepsis: efecto de protección renal de los antioxidantes / Lesão renal aguda induzida pela sepse: efeito de proteção renal dos antioxidantes

ABSTRACT Objective: To evaluate the antioxidant action of N-acetylcysteine and diosmin-hesperidin in an experimental model of sepsis-induced acute kidney injury in rats. Methods: The study used 20 Wistar adult male rats divided into the following groups: control (laparotomy with no induction of abdominal sepsis), sepsis (experimental model of sepsis with cecal ligation and puncture), N-acetylcysteine + sepsis and diosmin-hesperidin + sepsis. The evaluation contemplated physiological parameters (temperature, glycemia, and average blood pressure), kidney function (creatinine clearance), oxidative stress (urinary peroxides) and kidney histology. Results: The animals submitted to cecal ligation and puncture (sepsis) presented lower body temperature, lower average blood pressure, reduced creatinine clearance and increased urinary hydrogen peroxide levels. Treatment with diosmin-hesperidin improved kidney function and led to a reduction in the excretion of oxidative metabolites. Conclusion: The present study highlighted the protective antioxidant action of diosmin-hesperidin in the experimental model of sepsis-induced acute kidney injury.

RESUMEN Objetivo: Evaluar la acción antioxidante de agentes como la N-acetilcisteína y Diosmina-Hesperidina en modelo experimental de lesión renal aguda inducida por sepsis en ratones. Método: Fueron utilizados veinte ratones Wistar, adultos y machos, divididos en los grupos: Control (laparotomía sin inducción de sepsis abdominal), Sepsis (modelo experimental de sepsis con ligadura y punción de ciego-LPC), N-acelsisteína+Sepsis y Diosmina Hesperidina+Sepsis. Se evaluaron parámetros fisiológicos (temperatura, glucemia y presión arterial promedio), la función renal (clearance de creatinina), el estrés oxidativo (peróxidos urinarios) e histología renal. Resultados: Los animales sometidos a LPC (sepsis) presentaron reducción de la temperatura corporal, de la presión arterial promedio, del clearance de creatinina e incremento de niveles de peróxidos de hidrógeno urinarios. El tratamiento con Diosmina-Hesperidina mejoró la función renal, reduciendo la excreción de metabolitos oxidativos. Conclusión: Este estudio destacó la acción renoprotectora antioxidante de la Diosmina-Hesperidina en el modelo experimental de lesión renal aguda inducida por sepsis.

RESUMO Objetivo: Avaliar a ação antioxidante de agentes como a N-acetilcisteína e diosmina-hesperidina em modelo experimental de lesão renal aguda induzida pela sepse em ratos. Método: Foram utilizados vinte ratos Wistar, adultos e machos, divididos nos seguintes grupos: Controle (laparotomia sem indução de sepse abdominal), Sepse (modelo experimental de sepse com ligadura e punção do cécum- LPC), N-acetilcisteína+Sepse e Diosmina Hesperidina+Sepse. Foram avaliados parâmetros fisiológicos (temperatura, glicemia e pressão arterial média), função renal (clearance de creatinina), estresse oxidativo (peróxidos urinários) e histologia renal. Resultados: Os animais submetidos à LPC (sepse) apresentaram redução da temperatura corporal, da pressão arterial média, do clearance de creatinina e elevação nos níveis de peróxidos de hidrogênio urinários. O tratamento com a Diosmina-Hesperidina melhorou a função renal com redução na excreção dos metabólitos oxidativos. Conclusão: Este estudo destacou a ação renoprotetora antioxidante da Diosmina-Hesperidina no modelo experimental de lesão renal aguda induzida pela sepse.

Maximization of Extracted Condition of Pro-angiogenic Components in Citrus unshiu Peels using Dimethyl Sulfoxide

Aqueous extraction of Citrus unshiu peels (AECUP) is mainly comprised with pro-angiogenichesperidin and narirutin. In this study, we report approaches to increasing the yields of extracted hesperidin and narirutinfrom Citrus unshiu peels using proper solvents. Significantly improved yields of both compounds were obtained using methanol and dimethyl sulfoxide (DMSO) compared to acetonitrile, ethyl acetate, ethanol, and isopropyl alcohol. Especially, effect of DMSO was by far the better of the two solvents in extraction of hesperidin. In addition, the DMSO extracted hesperidin significantly induced the pro-angiogenic effects of human umbilical vein endothelial cells (HUVECs) and markedly up-regulated phosphorylation of the ERK1/2 signaling pathway. These results demonstrate that pro-angiogenic inducer; hesperidin and narirutin can be simply, easily, and effectively extracted from Citrus unshiu peels.

Hesperidin Attenuates Ultraviolet B-Induced Apoptosis by Mitigating Oxidative Stress in Human Keratinocytes

Human skin cells undergo pathophysiological processes via generation of reactive oxygen species (ROS) upon excessive exposure to ultraviolet B (UVB) radiation. This study investigated the ability of hesperidin (C28H34O15) to prevent apoptosis due to oxidative stress generated through UVB-induced ROS. Hesperidin significantly scavenged ROS generated by UVB radiation, attenuated the oxidation of cellular macromolecules, established mitochondrial membrane polarization, and prevented the release of cytochrome c into the cytosol. Hesperidin downregulated expression of caspase-9, caspase-3, and Bcl-2-associated X protein, and upregulated expression of B-cell lymphoma 2. Hesperidin absorbed wavelengths of light within the UVB range. In summary, hesperidin shielded human keratinocytes from UVB radiation-induced damage and apoptosis via its antioxidant and UVB absorption properties.

Simultaneous determination of diosmin and hesperidin in pharmaceuticals by RPLC using ionic liquids as mobile phase modifiers

Diosmin and hesperidin are natural flavonoid glycosides found in various plant materials, mainly in citrus fruits in different concentrations. Diosmin for pharmaceutical use is obtained mainly semi-synthetically from hesperidin. Hesperidin often accompanies diosmin as a natural impurity in different pharmaceutical formulations; therefore, a simple, fast and precise method for the simultaneous assay of diosmin and hesperidin in pharmaceutical formulations has been developed to control their contents. Chromatographic resolution was performed using a column with C-18 packing and the following mobile phase: methanol/water [45: 55, v/v] with 0.025% added didecyldimethylammonium lactate, which significantly affects retention, shortening analysis time and having a positive impact on the symmetry of resulting chromatographic peaks. The method shows linearity between 2.5 and 100 microg/mL, high repeatability [0.39 and 0.42% for diosmin and hesperidin, respectively] and accuracy of 96 to 102% for both the assayed compounds. Intraday and interday precision of the new method were less than RSD% 1, 2. The limit of detection of the assayed compounds is 2.5 and 1.2 microg/mL for diosmin and hesperidin, respectively. The method was tested on several pharmaceutical products available in Poland

Avaliação preliminar da associação entre anfotericina e hesperina com oxidantes e células huvec / Preliminary assessment of the association between amphotericin and hesperetin with oxididants and huvec cells

A anfotericina B (AmB) é fármaco o “padrão ouro” para o tratamento de infecções fúngicas invasivas desde 1960, Entretanto, a anfotericina B apresenta elevada toxicidade, a qual manifesta-se mais frequentemente nos rins e no fígado, Sabe-se, desde 1985, que a auto-oxidação da AmB origina diferentes formas de espécies reativas oxidativas e estas, por serem tóxicas para a célula, seriam responsáveis, em parte, pela toxicidade, Diferentes estudos indicam que a hesperidina contribui por meio do decréscimo do estresse oxidativo, para a proteção renal e contra a injúria gerada pela isquemia, Tal fato e o envolvimento da AmB na geração de radicais livres tornam interessante a avaliação preliminar do efeito da hesperidina e AmB (isoladamente ou associadas) frente a espécies reativas do oxigênio e radicais livres, bem como o estudo das mesmas em modelos de citoxicidade, Frente ao ABTS•+, a AmB apresentou IC50 igual a 0,0124mg/mL, mas quando associada à hesperidina este valor caiu para 0,0003mg/mL, Frente ao HOCl, a Amb apresentou IC50 igual a 0,0056, mas quando associada à hesperidina este valor caiu para 0,0023mg/mL, No ensaio com DPPH• e radical ânion superóxido as amostras não foram efetivas, No ensaio com células endoteliais em cultivo (HUVEC), as associações reduziram a viabilidade celular, Estes resultados preliminares evidenciam a interação dos compostos com espécies reativas bem como indicam possibilidade de exacerbação do dano pela AmB na presença dos antioxidantes em um modelo in vitro...

Amphotericin B (AmB) is drug “gold standard” for the treatment of invasive fungal infections since 1960. However, amphotericin B has high toxicity, which manifests itself most often in the kidneys and in the liver. It is known, since 1985, that self-oxidation of AmB gives different forms of reactive oxidative species and these, being toxic to the cell, would be responsible, in part, by its toxicity. Different studies indicate that hesperidin contributes, through the reduction of oxidative stress, to protect against renal injury generated by ischemia. This fact and the involvement of AmB in the generation of free radicals make it interesting the preliminary evaluation of the effect of hesperidin and AmB (alone or associated) against reactive oxygen species and free radicals, as well as the study on models of cytotoxicity. Front ABTS•+, AmB presented IC50 equal to 0.0124 mg/mL, but when it was associated to hesperidin this value has decreased to 0.0003 mg/mL. Front HOCl, Amb presented IC50 equal to 0.0056, but when it was associated to hesperidin this value has decreased to 0.0023 mg/mL. In the trials with DPPH• and the superoxide anion radical samples were not effective. In the assay with endotelial cell culture (HUVEC cells), the association has decreased cell viability. These preliminary results demonstrate the interaction of the compounds with reactive species as well as indicate the possibility of damage exacerbation by AmB in the presence of antioxidants in an in vitro model...

Prevenção da nefrotoxicidade da anfotericina B por meio do uso de fitomedicamentos / Prevención de la nefrotoxicidad por anfotericina B utilizando fito / Prevention of amphotericin B nephrotoxicity through use of phytotherapeutic medication

RESUMO Objetivo Avaliar ação renoprotetora dos flavonoides diosmina e hesperidina na prevenção da nefrotoxicidade da anfotericina B em modelo experimental com ratos. Método Ratos Wistar, adultos, machos foram distribuídos nos seguintes grupos: Salina; diosmina hesperidina (animais receberam 50 mg/kg de diosmina hesperidina em água de bebedouro por dez dias); Anfotericina B (animais receberam 15 mg/kg/dia de anfotericina B intraperitoneal por cinco dias); Anfotericina B+diosmina hesperidina. Foram avaliados função renal, fração de excreção de sódio, potássio e magnésio e os metabólitos oxidativos. Resultados O tratamento com anfotericina B reduziu a função renal, vista peloclearance de creatinina, elevou os marcadores de função tubular como a fração de excreção de sódio, potássio, magnésio e dos metabólitos oxidativos. O pré-condicionamento com diosmina hesperidina elevou o clearance de creatinina e atenuou da lesão tubular e oxidativa. Conclusão A administração de anfotericina B resultou no declínio da função renal com lesão tubular e a diosmina hesperidina demonstrou efeito renoprotetor antioxidante.

RESUMEN Objetivo Evaluar la acción renoprotetora de flavonoides, diosmina y hesperidina en la prevención de la nefrotoxicidad de Anfotericina B en un modelo experimental de animales. Método Ratones Wistar, adultos y machos distribuidos en los grupos: Salina (controle); Diosmina Hesperidina (50 mg/kg de diosmina hesperidina en agua, durante diez días); Anfotericina B (15 mg/kg de anfotericina B intraperitoneal durante cinco días); Anfotericina B+Diosmina Hesperidina. Función renal, la excreción fraccional de sodio, potasio en magnesio en los metabolitos oxidativos se realizaron. Resultado El tratamiento con anfotericina B reduce el clearance de creatinina, aumento de la fracción de excreción de sodio, potasio, magnesio y metabolitos oxidativos. El pretratamiento con hesperidina diosmina aumentó el aclaramiento de creatinina y la atenuación del daño tubular y oxidativa. Conclusión La administración de anfotericina B dio como resultado la disminución de la función renal con lesión tubular y la diosmina hesperidina demostró efecto renoprotector antioxidante.

ABSTRACT Objective To evaluate the effect of diosmin and hesperidin flavonoids in the prevention of amphotericin B nephrotoxicity, through an experimental model on rats. Method Adult, male Wistar rats were distributed into the following groups: saline; diosmin hesperidin (animals that received 50 mg/kg of diosmin hesperidin, drinking water, for ten days); amphotericin B (animals that received 15 mg/kg/day of amphotericin B through intraperitoneal treatment for five days); amphotericin B+diosmin hesperidin. Renal function, fractional excretion of sodium; potassium and magnesium and oxidative metabolites were evaluated. Results Treatment with amphotericin B reduced renal function, as shown by the clearance of creatinine, increased tubular function markers and fractional excretion of sodium, potassium, magnesium and oxidative metabolites. Pre-treatment with diosmin hesperidin ameliorated clearance of creatinine and reduced tubular and oxidative injury. Conclusion Administration of amphotericin B resulted in reduction of renal function with tubular injury, and diosmin hesperidin showing an antioxidant protective effect on the kidneys.

Effect of hesperidin on TGF-beta1/Smad signaling pathway in HSC / 中国中药杂志

Liver fibrosis is a common pathological process for chronic liver injury caused by multiple etiological factors and an inevitable phase leading to liver cirrhosis. According to the previous studies, hesperidin (HDN) shows a very good protective effect on CCl4-induced chemical hepatic fibrosis in rats. In this experiment, based on the findings of the previous studies, a platelet-derived growth factor (PDGF)-induced HSC-T6 model was established to observe the inhibitory effect of HDN on HSC-T6 proliferation. The ELISA method was adopted to detect the content of collagen I in HSC-T6 supernatant. Transforming growth factor (TGF)-beta1, Smad2, Smad3, Smad7 and connective tissue growth factor (CTGF) mRNA expressions were measured by RT-PCR; TGF-beta1 and CT-GF protein expressions in HSC-T6 were determined by Western blot, in order to study HDN's effect on TGF-beta1 signaling pathway in HSC and its potential action mechanism. The results demonstrated that HDN could notably improve HSC-T6 proliferation, Collagen I growth and TGF-beta1, Smad2, Smad3 and CTGF mRNA.expressions. After being intervened with HDN, it could notably inhibit HSC-T6 proliferation and Collagen I growth, reduce TGF-beta1, Smad2, Smad3 and CTGF mRNA and TGF-beta1, CTGF protein expressions and increase Smad7 mRNA expression. HDN's antihepatic fibrosis effect may be related to the inhibition of HSC proliferation and activation by modulating TGF-beta/Smad signaling pathway.

Inhibitory Effects of Yuzu and Its Components on Human Platelet Aggregation

Our previous study demonstrated that yuzu has an anti-platelet effect in rat blood. In the present study, we examined whether the anti-platelet effect of yuzu can be extended to human blood by investigating its ability to inhibit aggregations induced by various agonists in human platelet rich plasma (PRP). This study also investigated the underlying mechanism of yuzu focusing on ADP granule secretion, TXB2 formations, and PLCgamma/Akt signaling. The results from this study showed that ethanolic yuzu extract (YE), and its components, hesperidin and naringin, inhibited human platelet aggregation in a concentration-dependent manner. YE, hesperidin and naringin also inhibited TXB2 formation and ADP release. The phosphorylation of PLCgamma and Akt was significantly inhibited by YE, heperidin and naringin. Furthermore, we demonstrated that YE, heperidin and naringin has anti-platelet effects in rat ex vivo studies, and lower side effects in mice tail bleeding time studies. The results from this study suggest that YE, hesperidin and naringin can inhibit human platelet aggregation, at least partly through the inhibition of PLCgamma and Akt, leading to a decrease in TXB2 formation and granule secretion.

The relaxing effect of Poncirus fructus and its flavonoid content on porcine coronary artery / 한국실험동물학회지

Coronary artery disease is a common occurrence in human, and causes enormous social cost. Poncirus fructus (PF), the dried immature fruits of Poncirus trifoliata Rafinesquem, is used in the treatment of womb contraction and dyspepsia, as a prokinetic, and in improving blood circulation. This study was performed to investigate the effects of PF and some of its flavonoids components on the coronary from the pig. The arterial ring was suspended by a pair of stainless steel stirrups in an organ bath. The end of the upper stirrup was connected to an isometric force transducer. A dose-dependent induction of relaxation was observed by both water and 70% ethanol extracts of PF in the porcine coronary artery precontracted with U46619 (100 nM), a stable analogue of the potent vasoconstrictor thromboxane A2. The 70% ethanol extract showed more efficacy than the water extract. Pretreatment of the artery with L-NAME (100 microM), a nitric oxide synthase inhibitor, resulted in a significant reduction in the relaxation induced by PF extract. In addition, ODQ (10 microM), a soluble guanylate cyclase inhibitor, also significantly reduced the effects of PF extracts. Hesperidin, a flavonoid present in PF, induced very weak relaxation of the porcine coronary artery at a high concentration (100 microM), while its aglycone, hesperetin, demonstrated a dose-dependent relaxation. In conclusion, PF extracts induced relaxation in the porcine coronary artery, partially through the nitric oxide-cGMP pathway, and the aglycones of flavonoids might be also involved in the relaxation of the same artery.

Optimization of Extraction Condition of Hesperidin in Citrus unshiu Peels using Response Surface Methodology

Hesperidin, which is the most abundant flavonoid of Citrus unshiu (Rutaceae), has been reported to possess diverse activities and widely used as functional foods and cosmetics. For the development of functional products, extraction procedure is indispensable. Extraction conditions affect the composition of extract as well as its biological activity. Therefore, we tried to optimize extraction conditions such as extraction solvent, extraction time and extraction temperature for maximum yield of hesperidin using response surface methodology with threelevel-three-factor Box-Behnken design (BBD). Regression analysis showed a good fit of the experimental data and the optimal condition was obtained as ethanol concentration, 59.0%; temperature 71.5degrees C and extraction time, 12.4 h. The hesperidin yield under the optimal condition was found to be 287.8 microg per 5 mg extract, which was well matched with the predicted value of 290.5 microg. These results provides optimized extraction condition for hesperidin and might be useful for the development of hesperidin as functional products like health supplements, cosmetics and medicinal products.

Effect of different compatibility of zhizi dahuang decoction on pharmacokinetics of naringenin and hesperetin / 中国中药杂志

An HPLC-UV method was developed for the determination of total naringenin and total hesperetin in rat plasma after oral administration of Citrus aurantium Immaturus extracts and Zhizi Dahuang decoction. Plasma samples were pretreated with liquid-liquid extraction procedure and acid hydrolysis method was used for converting conjugated naringenin and hesperetin to their respective free forms. Plasma samples were separated on a C18 column (4.6 mm x 150 mm, 5 microm), using 0.1% phosphoric acid and methanol as mobile phase at a flow rate of 1.0 mL x min(-1) with gradient elution. DAS 2.0 software was applied to calculate the pharmacokinetic parameters while the SPSS 16.0 software was used for statistical analysis. Significant differences were observed, the C(max) AUC(0-t) of total naringenin in ZS group was 73.5% and 65.9% higher than those in ZZDHD group, respectively; the C(max), AUC(0-t) of total hesperetin in ZS group was 63.5% and 119.1% higher than those in ZZDHD group, respectively. There is a obvious decrease in C(max) and AUC(0-t) of total naringenin and total hesperetin after compatibility and their pharmacokinetic characteristics changed greatly due to the combination of other herbs. The established method was rapid, sensitive, selective and accurate, and it could be applied in the determination of total naringenin and total hesperetin in rat plasma.

Pull-out bond strength of a self-adhesive resin cement to NaOCl-treated root dentin: effect of antioxidizing agents

OBJECTIVES: This study evaluated the effect of three antioxidizing agents on pull-out bond strengths of dentin treated with sodium hypochlorite. MATERIALS AND METHODS: Root canals of 75 single-rooted human teeth were prepared. Fifteen teeth were irrigated with normal saline for a negative control group, and the remaining 60 teeth (groups 2 - 5) with 2.5% NaOCl. The teeth in group 2 served as a positive control. Prior to post cementation, the root canals in groups 3 - 5 were irrigated with three antioxidizing agents including 10% rosmarinic acid (RA, Baridge essence), 10% hesperidin (HPN, Sigma), and 10% sodium ascorbate hydrogel (SA, AppliChem). Seventy-five spreaders (#55, taper .02, Produits Dentaires S.A) were coated with silica and silanized with the Rocatec system and ceramic bond. All the prepared spreaders were cemented with a self-adhesive resin cement (Bifix SE, Voco Gmbh) in the prepared canals. After storage in distilled water (24 h/37degrees C), the spreaders were pulled out in a universal testing machine at a crosshead speed of 1.0 mm/min. Pull-out strength values were analyzed by one-way ANOVA and Tukey's HSD test (alpha = 0.05). RESULTS: There were significant differences between study groups (p = 0.016). The highest pull-out strength was related to the SA group. The lowest strength was obtained in the positive control group. CONCLUSIONS: Irrigation with NaOCl during canal preparation decreased bond strength of resin cement to root dentin. Amongst the antioxidants tested, SA had superior results in reversing the diminishing effect of NaOCl irrigation on the bond strength to root dentin.