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Antidepressant-Like Effects of Hesperidin in Animal Model of Post-Traumatic Stress Disorder

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Chinese Journal of Integrative Medicine 2021年第1期27卷 39-46页

作者： Bombi Lee Gwang Muk Choi Bongjun Sur Acupuncture and Meridian Science Research Center College of Korean MedicineKyung Hee UniversitySeoul(02447)Republic of Korea Center for Converging Humanities Kyung Hee UniversitySeoul(02447)Republic of Korea The Graduate School of Basic Science of Medicine College of MedicineKyung Hee UniversitySeoul(02447)Republic of Korea Dopartmont of Molcoular Mcdicine and TIDRC School of MedicineEwha Womans UniversitySeoul(07985)Republic of Korea

Objective:Post-traumatic stress disorder(PTSD)is a psychiatric disorder characterized by depression and anxiety,that arises due to an imbalance of neurotransmitters in response to excessive stress.Hesperidin(HSD)is a naturally occurring flavonoid shown to exert a variety of biological activities,including antioxidant,anti-inflammatory,and neuroprotective effects.Methods:This study was used the open field test(OFT)and forced swimming test(FST)to examine the effects of HSD on the depression-like response of rats after exposure to a single prolonged stress(SPS)leading to the dysregulation of the serotonergic activation system.Male rats were given HSD(20,50,and 100 mg/kg,intraperitoneal injection,n=6–7 per group)once daily for 14 days after exposure to SPS.The influence of administration of HSD on SPS-induced behavioral responses and concentrations of serotonin(5-HT),5-hydroxyindoleacetic acid(5-HIAA),and monoamine oxidase-A(MAO-A)in the rat brain were also investigated using enzyme-linked immunoassays(ELISAs).Results:Daily HSD administration significantly improved depression-like behaviors in the FST(P<0.05),increased the number of lines crossed in the central zone of the OFT(P<0.01),and reduced freezing behavior both in contextual and cued fear conditioning.HSD treatment also attenuated the reduction in SPS-induced 5-HT concentrations in the hippocampus and amygdala.This increase in 5-HT concentrations during HSD treatment was partially attributed to a decrease in the 5-HIAA/5-HT ratio in the hippocampus of rats with PTSD.Furthermore,HSD treatment inhibited activity of MAO-A and decreases of tryptophan hydroxylase-1 expression in the hippocampus.Conclusion:HSD was shown to exert antidepressant effects in rats exposed to SPS,suggesting that this natural flavonoid may be an effective medicine for PTSD.

关键词： Hesperidin post-traumatic stress disorder depression serotonin

Hesperidin as a preventive resistance agent in MCF-7 breast cancer cells line resistance to doxorubicin

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Asian Pacific Journal of Tropical Biomedicine 2014年第3期4卷 228-233页

作者： Rifki Febriansah Dyaningtyas Dewi P.P. Sarmoko Nunuk Aries Nurulita Edy Meiyanto Agung Endro Nugroho Cancer Chemoprevention Research Center Faculty of PharmacyUniversitas Gadjah Mada YogyakartaIndonesia Pharmacy study programme Faculty of Medicine and Health SciencesUniversitas Muhammadiyah YogyakartaYogyakartaIndonesia Faculty of Pharmacy Universitas Jenderal SoedirmanPurwokertoIndonesia Faculty of Pharmacy Universitas Muhammadiyah PurwokertoPurwokertoIndonesia

Objective:To evaluate of Hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells(MCF-7/Dox)in cytotoxicity apoptosis and P-glycoprotein(Pgp)expression in combination with doxorubicin.Methods:The cytotoxic properties.50%inhibition concentration(IC_(50))and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin(MCF-7/Dox)cells were determined using MTT assay.Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange.Immunocytochemistry assay was performed to determine the level and localization of Pgp.Results:Single treatment of Hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC_(50)value of 11μmol/L.Thus,combination treatment from Hesperidin and doxorubicin showed addictive and antagonist effect(CI>1.0).Hesperidin did not increase the apoptotic induction,but decreased the Pgp expressions level when combined with doxorubicin in low concentration.Conclusions:Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC_(50)of 11μmol/L.Hesperidin did not increased the apoptotic induction combined with doxorubicin.Cochemotherapy application of doxorubicin and Hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.

关键词： Hesperidin Doxorubicin MCF-7/Dox cells line Apoptosis Pgp expression

Impact of citrus fruit and Hesperidin intake on multiple health outcomes:An umbrella review

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Journal of Nutritional Oncology 2023年第1期8卷 16-24页

作者： Yu-Sen Cheng Yong Zhou Division of Gastrointestinal Surgery Department of General SurgeryWest China HospitalSichuan UniversityChengduSichuanChina

Citrus fruits are rich sources of several biologically active flavonoids such as Hesperidin,naringin,and polymethoxylated flavones.We evaluated the evidence of associations between citrus fruit or Hesperidin intake and multiple health outcomes.An umbrella review was conducted for studies performed in humans.Overall,246 articles were initially identified by searching in 4 databases.Twenty-two meta-analyses and systematic reviews with 28 health outcomes met the inclusion criteria.Citrus fruit intake had beneficial effects on all-cause mortality(relative risk[RR].0.90;95%confidence interval[95%CI],0.86 to 0.94),cardiovascular diseases(RR,0.78;95%CI,0.66 to 0.92),coronary heart disease(RR,0.91;95%CI,0.86 to 0.96),stroke(RR,0.74;95%CI,0.65 to 0.84),type 2 diabetes mellitus(RR,0.85;95%CI,0.78 to 0.92),and several cancers.Dose-response analyses indicated that each 100-g/d increase in citrus fruit intake could reduce the risks of all-cause mortality by 6%(RR,0.94;95%CI,0.88 to 1.00),stroke by 22%(RR,0.78;95%CI,0.69 to 0.90),and cardia gastric cancer by 40%(RR,0.60;95%CI,0.44 to 0.83).Citrus fruit intake also had beneficial effects on the lipid profile and body weight control(weighted mean difference,−1.28;95%CI,−1.82 to−0.74).Grapefruits could reduce the systolic blood pressure(weighted mean difference,−2.43,95%CI,−4.77 to−0.09).Hesperidin supplementation significantly improved inflammation.Citrus fruit intake was generally safe and beneficial for multiple health outcomes in humans.However,grapefruit and pomelo juice may affect the bioavailability of various medications,so care should be exercised before increasing the intake of these fruits or their juices.

关键词： Citrus fruit Hesperidin Health Umbrella review Meta-analysis Systematic review

Targets and molecular mechanisms of a citrus flavonoid, Hesperidin, against luminal breast cancer cells: an integrative bioinformatics analysis

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Asian Pacific Journal of Tropical Biomedicine 2019年第12期9卷 531-538页

作者： Adam Hermawan Herwandhani Putri Department of Pharmaceutical Chemistry Faculty of PharmacyUniversitas Gadjah MadaSekip Utara Ⅱ55281 YogyakartaIndonesia Cancer Chemoprevention Research Center Faculty of PharmacyUniversitas Gadjah MadaSekip Utara Ⅱ55281 YogyakartaIndonesia

Objective:To identify the potential target and mechanisms of Hesperidin in MCF-7 estrogen receptor-positive breast cancer cells using bioinformatics approaches.Methods:Gene expression profiles were accessed from public database GSE85871.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was carried out with Database for Annotation,Visualization and Integrated Discovery.The protein-protein interaction network was analyzed by STRING-DB and visualized by Cytoscape.Transcription factor regulatory networks were constructed from TRED,TRRUST,Reg Network and visualized by Cytoscape.Drug association analysis was conducted by Web Gestalt.Results:GO and KEGG pathway enrichment analysis revealed biological processes,cellular components and molecular functions that were related to cancer and estrogen signaling pathways.KEGG pathway enrichment analysis of the genes in transcription factor-differential expression genes regulatory network showed regulation of cancer,estrogen signaling pathways,epidermal growth factor receptor tyrosine kinase inhibitor resistance,and endocrine resistance.Moreover,drug association analysis revealed that Hesperidin affected the expression of the same gene as raloxifene.Conclusions:Hesperidin targets estrogen receptor signaling in estrogen receptor-positive breast cancer cells.Results of this study could trace the molecular mechanism of Hesperidin in estrogen receptor-positive breast cancer cells and integrative bioinformatics analysis could accelerate drug discovery and development.

关键词： Hesperidin Breast cancer Bioinformatics Estrogen receptor Signaling pathway

Quantitative estimation of Hesperidin by HPTLC in different varieties of citrus peels

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Asian Pacific Journal of Tropical Biomedicine 2014年第4期4卷 262-266页

作者： Prawez Alam Aftab Alam Khalid Anwer Saleh I Alqasoumi Department of Pharmacognosy College of PharmacySalman Bin Abdulaziz University Department of Pharmaceutics College of PharmacySalman Bin Abdulaziz University Department of Pharmacognosy College of PharmacyKing Saud University

Objective:To develop a simple,selective,sensitive and accurate high-performance thin layer chromatography(HPTLC)method to determine the quantity of Hesperidin in different varieties of citrus fruits.Methods:The method was carried out in aluminum-backed silica gel 60 F_(254)plates with ethyl acetate-methanol-water 15:3:2(%,v/v)as mobile phase.Results:A compact band was obtained for Hesperidin at R_f value of(0.40±0.04).The calibration plot was linear in the range of 100-800 ng/spot of Hesperidin and the correlation coefficient of 0.9986was indicative of good linear dependence of peak area on concentration.Limit of detection(8.87ng/spot),limit of quantification(23.21 ng/spot),accuracy(less than 2%)and recovery(ranging from98.55-99.38)were found satisfactory.Conclusions:The method developed can be used for routine analysis of Hesperidin in crude drug as well as in herbal and pharmaceutical dosage form containing citrus fruits as an ingredient.

关键词： HPTLC Citrus Hesperidin

Neuroprotective Effects of Hesperidin and Benfotiamine against Paraquat Induced Spinal Cord Neurotoxicity in Adult Male Albino Rats

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Occupational Diseases and Environmental Medicine 2021年第3期9卷 139-164页

作者： Dalia M. Amin Shimaa H. Ameen Marwa T. Abaza Forensic Medicine and Clinical Toxicology Department Faculty of Medicine Zagazig University Zagazig Egypt

Introduction: There are extensive people exposures to paraquat (PQ) herbicide resulting in human health hazards. Aim of the Work: To compare the beneficial neuroprotective effects of Hesperidin and benfotiamine on paraquat (PQ)-induced spinal cord neurotoxic effects in rats. Materials and Methods: Rats were divided into 4 groups as following: control, paraquat (PQ 20.8 mg/kg, oral gavage (e.g.)), paraquat + benfotiamine (50 mg/kg, oral gavage (e.g.)) and paraquat + Hesperidin (40 mg/kg, oral gavage (e.g.)). PQ is given as the previous dose. Rats are treated 6 days per week. Results: There was a significant increased mean value of malondialdehyde associated with a significant reduction in the content of reduced glutathione and antioxidant enzymes activities associated with a significant increase in Serum phosphorylated neurofilament-H, neurospecific enolase and s100 levels were recorded and significant spinal cord histopathological changes in paraquat treated group as compared to their corresponding values in the control group and immunohistochemical examination confirmed these results. Upon supplementation with benfotiamine and Hesperidin to paraquat treated rats, there was a significant decrease in the mean values of malondialdehyde associated with a marked increase in the content of reduced glutathione and antioxidant enzymes activities associated with a significant decrease in Serum phosphorylated neurofilament-H, neurospecific enolase and s100 levels were also recorded with significant improvement of spinal cord architecture when compared with the paraquat treated group. Conclusion: The use of benfotiamine and Hesperidin produced a significant protection against all of the above-mentioned changes.

关键词： Benfotiamine Hesperidin Paraquat Spinal Cord Toxicity

Myricetin and Hesperidin Inhibit Cerebral Thrombogenesis and Atherogenesis in Apoe-/-and Ldlr-/-Mice

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Food and Nutrition Sciences 2018年第1期9卷 20-31页

作者： Yasuto Sasaki Kanae Hyodo Ayana Hoshino Eri Kisa Koichi Matsuda Yoko Horikawa John C. Giddings Laboratory of Physiology Faculty of Nutrition Kobe Gakuin University Kobe Japan Laboratory of Biochemistry Faculty of Nutrition Kobe Gakuin University Kobe Japan Department of Haematology School of Medicine Cardiff University Cardiff UK

Flavonoids have been reported to possess strong antioxidant activities that moderate endothelial dysfunction and demonstrate protective effects on cardiovascular disease. Our previous studies confirmed that flavonoids, including Hesperidin, naringin and nobiletin, inhibited thrombogenesis and hypertension in stroke prone spontaneously hypertensive rats (SHRSP) by protecting the endothelium from the adverse effects of free radical formation. We have now further investigated the protective effects of myricetin and Hesperidin on cerebral thrombosis and atherogenesis in apolipoprotein E (apoE) and lowdensity lipoprotein receptor (LDLR) deficient (Apoe-/- and Ldlr-/- double knockout) mice. Three groups of mice were fed high fat diet alone and high fat diet mixed with myricetin (100 mg/kg/day and 200 mg/kg/day) or glucosyl Hesperidin (G-Hesperidin;250 mg/kg/day and 500 mg/kg/day) for 8 weeks. There were no differences in body weight related to administration of the flavonoids. Thrombotic tendency was assessed using a He-Ne laser technique in the murine cerebral pial vessels. In addition, atherogenesis was quantified histologically after dissection of the aorta from each mouse and staining with Oil Red O solution. The percentages of stained area to whole area of dissected aorta were calculated as indices of anti-atherogenic activity. Both myricetin and G-Hesperidin significantly inhibited thrombogenesis in vivo and significantly inhibited atherogenesis compared to control mice (p Hesperidin suppressed the development of atherogenesis and thrombogenesis, possibly associated with the potent antioxidant effects of the flavonoids.

关键词： Myricetin Hesperidin Atherosclerosis Apoe-/- and Ldlr-/- Mice Thrombosis

Anticataractogenic effect of Hesperidin in galactose-induced cataractogenesis in Wistar rats

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World Journal of Ophthalmology 2016年第1期6卷 1-9页

作者： Ramar Manikandan Munuswamy Arumugam Departmen of Zoology University of Madras

AIM: To explore the anticataractogenic potential of Hesperidin, a flavanone, in galactose-induced cataractogenesis.METHODS: In this study, cataract was induced by administering galactose enriched food in a set of rats. Effect of different dosages of Hesperidin(25, 50 and 75 mg/kg body weight) were administered simultaneously with galactose in prevention of cataract was determined in another set. In both sets of animals, the levels of peroxidation, oxidants(NO and OH), antioxidants(enzymatic: Superoxide dismutase, catalase, glutathione S-transferase, GPx and non-enzymatic: Reduced glutathione, vitamin E), aldose reductase and sorbitol were determined in the eye lens. In addition, glucose and lipid peroxidation levels were also tested in serum. The quantitative changes in lens inducible nitric oxide synthase(iN OS) and its expression were also determined using Western blot and real-time polymerase chain reaction analyses.RESULTS: Galactose enriched food produced cataract in both the eye lens as a sequel to elevated serum glucose. Simultaneous administration of Hesperidin not only reduced serum glucose but also prevented cataract development, through reduced levels of reactive oxygen species(NO and OH) and i NOS expression as well as elevated enzymic and non-enzymic antioxidants were observed in the eye lens.CONCLUSION: These results indicate the preventive effect of Hesperidin against cataract in hyperglycemic rats.

关键词： Antioxidants Oxidative stress Galactoseinduced cataract Free radicals Hesperidin Eye lens

Reliability of online near-infrared spectroscopy analysis of the ex-traction process of Huatan Qushi decoction for phlegm-dampness constitution

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Journal of Traditional Chinese Medicine 2017年第6期37卷 804-809页

作者： Zhao Shipeng Zheng Yanfei Li Pin Liang Xue Bao Lei Chen Yu Yu Ruoxi Sun Ranran Li Lingru Wang Qi College of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China

OBJECTIVE: To establish a quantitative model for the online analysis of Hesperidin content in the extraction process of Huatan Qushi decoction for individuals with phlegm-dampness constitution by using near-infrared(NIR) spectroscopy and partial least squares(PLS) methods.METHODS: The reference content of Hesperidin, an effective ingredient of Huatan Qushi decoction,was determined using high-performance liquid chromatography(HPLC). The modeling band was selected using synergy interval PLS(Si PLS) algorithms, and a PLS model demonstrating the relationship between NIR predictive values and HPLC reference values was established. The optimal modeling route was selected through global optimization of process trace parameters.RESULTS: The root mean square error of cross-validation was 9.8410. The coefficients of determination of the calibration set and prediction set were0.9860(R2 cal) and 0.9458(R_(cal)~2), respectively. The residual predictive deviation was 3.0115. The parameters demonstrated high predictive capability and reliability. The band was selected via the Si PLS method. There were seven latent variables.CONCLUSION: This study provides a favorable comprehensive evaluation method for variable selection and quality control of the Traditional Chinese Medicine extraction process.

关键词： Spectroscopy, near-infrared Least-squares analysis Hesperidin Phlegm dampness Huatan Qushi decoction