Hesperidin: Publications and Research from SwissMixIt

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HESPERIDIN :http://88swiss.com/hesperidin/index.htm

Hesperidin is a plant chemical that is classified as a bioflavonoid. It is most commonly found in citrus fruits, and used in medicine. Hesperidin, alone or in combination with other citrus bioflavonoids (such as diosmin), is most commonly used for blood vessel conditions such as hemorrhoids, varicose veins, and poor circulation (venous stasis). Hesperidin may help blood vessels function better. It may also reduce inflammation. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against development of neurodegenerative diseases.

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Keywords: hesperidin, new-clean process extraction, nanocrystals, antioxidant, anti-ageing, Apigenin, Hesperidin, Downregulate DNA Repair Genes, MCF-7, Breast Cancer Cells, Augment Doxorubicin Toxicity, Blood-Brain Barrier, hypoxia, CVD, bioavailability, cardiovascular disease, citrus fruits, coronavirus, COVID-19, flavonoids, hesperetin, hesperidin, hydrodynamic cavitation, pectin, SARS-CoV-2, autophagy, COVID-19, immune response, inflammation, Nigella sativa, oxidative stress, SARS-CoV-2 infection, Coronavirus, SARS-CoV-2, COVID-19, thymoquinone, chloroquine, hydroxychloroquine, SARS-CoV-2, COVID-19, Hesperidin, Prophylaxis, Treatment, Viral entry, Anti-viral activity, Immunity, Hesperidin, Neuroinflammation, Antioxidant, Demyelination, Hippocampus, high-fat diet, physical activity, oxidative stress, antioxidants, obesity, physical exercise, supplementation, flavonoids, reactive oxygen species, apigenin, doxorubicin, hesperidin, DNA repair, DNA damage, oxidative stress, Hesperidin, necrosis, skin carcinoma A431 cells, ROS, Hesperidin, Colon Cancer, HCT116, P53, Pifithrin-a, Bax, P21, Diet, flavonoids, human cancers, prevention, treatment, Hesperetin, hesperidin, radical-scavenging activity, inhibition rate co

Summary of Abstracts:

Effects of 8 Weeks of 2S-Hesperidin Supplementation on Performance in Amateur Cyclists [ Supplementation with an orange extract (2S-hesperdin) 500 mg/day improves estimated FTP and maximum power performance in amateur cyclists. ] 2S-Hesperidin is a flavanone (flavonoid) found in high concentrations in citrus fruits. It has an antioxidant and anti-inflammatory effects, improving performance in animals. This study investigated the effects of chronic intake of an orange extract (2S-hesperidin) or placebo on non-oxidative/glycolytic and oxidative metabolism markers and performance markers in amateur cyclists. Supplementation with an orange extract (2S-hesperdin) 500 mg/day improves estimated FTP and maximum power performance in amateur cyclists.

New Sustainable Process for Hesperidin Isolation and Anti-Ageing Effects of Hesperidin Nanocrystals [ May be used in skin cream to reduce dark eye circles. ] Hesperidin, a secondary orange (Citrus sinensis) metabolite, was extracted from orange bagasse. No organic solvents or additional energy consumption were used in the clean and sustainable process. Hesperidin is a known supplement due to antioxidant, chelating, and anti-ageing properties. Herein, hesperidin application to eliminate dark eye circles, which are sensitive and thin skin regions, was studied. It was shown that one of the nanonized hesperidin formulations was the most skin-friendly and might be used in cosmetics. Hesperidin, as other flavonoids, can reduce the intensity of tryptophan or other fluorophores of enzyme fluorophores of enzyme fluorescence emissions. Hesperidin chelates zinc(II) ion, which is in the catalytic site of the enzyme, catalytic site of the enzyme, and changes the conformation of the protein. There are already various and changes the conformation of the protein. There are already various studies in which it has been proven that flavonoids have an inhibitory effect on metalloproteinase (collagenase, elastases, and (collagenase, elastases, and hyaluronidases) by chelating their metal ions. Many other polyphenols, such as phenolic acid, flavonoids, coumarins, stilbenes, and lignans, are the most important polyphenols used in traditional and modern cosmetic and dermatologic products. Flavonoids have an influence on skin microcirculation and can be used as ingredients in creams for vascular, oily, and/or atypical skin. One of the interesting physical chemical properties of bioflavonoids is their ability to absorb ultraviolet radiation due to the presence of the conjugated double bonds in their structure. The polyphenol concentrations used in cosmetics cannot replace conventional UV filters. Additionally, phenolic compounds may have antimicrobial properties and assist in the preservation of cosmetic products against secondary infections. Low drug permeability through human epidermis can be ameliorated using penetration enhancers (compounds such as surfactants, terpenes, lipophilic solvent, and fatty acids), which modify the permeability of the skin barrier reversibly. Quercetin shows poor permeability even in the presence of the enhancers, due to its absolute insolubility in water. Several authors suggested that the permeability of this compound can be increased by uploading flavonoids in liposomes or other kinds of carrier systems. In the skin, HSD may significantly stimulate epidermal hyperplasia and improve epidermal permeability through epidermal proliferation, osteoblasts differentiation, and lipid secretion. The possibility of affecting tyrosinase activity, and the practical application thereof in the field of anti-ageing preparations designed to prevent lentigo senilis and lentigo solaris makes HSD remarkably interesting for skin whitening. Chelation properties of HSD are particularly important for skin bleaching activities, as well as HSD interaction with the tyrosinase during catalytic production of melanin. Tyrosinase has copper(II) in the active site, which is responsible for tyrosinase oxidation activities.

Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity A number of studies have confirmed anti-tumor activity of flavonoids and their ability to enhance the effectiveness of classical anticancer drugs. The mechanism of this phenomenon is difficult to explain because of the ambivalent nature of these compounds. Many therapeutic properties of these compounds are attributed to their antioxidant activity; however, it is known that they can act as oxidants. In conclusion, both apigenin and hesperidin enhance the cytotoxic effects of doxorubicin on breast cancer cells, and this phenomenon occurs regardless of oxidative stress but is accompanied by disorders of DNA damage response mechanisms.

Yuzu and Hesperidin Ameliorate Blood-Brain Barrier Disruption during Hypoxia via Antioxidant Activity [ May be good for prevention of neurodegenerative diseases. ] Yuzu and its main component, hesperidin (HSP), have several health benefits owing to their anti-inflammatory and antioxidant properties. We examined the effects of yuzu and HSP on blood–brain barrier (BBB) dysfunction during ischemia/hypoxia in an in vivo animal model and an in vitro BBB endothelial cell model, and also investigated the underlying mechanisms. Collectively, these results indicate that yuzu and HSP protect the BBB against dysfunction via maintaining integrity of claudin-5 and ZO-1, and these effects of yuzu and HSP appear to be a facet of their antioxidant properties. Our findings may contribute to therapeutic strategies for BBB-associated neurodegenerative diseases.

Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability Recently, hesperidin, a flavonone mainly present in citrus fruits, has emerged as a new potential therapeutic agent able to modulate several cardiovascular diseases (CVDs) risk factors. Hesperidin has shown glucose-lowering and anti-inflammatory properties in diabetic models, dyslipidemia-, atherosclerosis-, and obesity-preventing effects in CVDs and obese models, and antihypertensive and antioxidant effects in hypertensive models.

Review of Evidence Available on Hesperidin-Rich Products as Potential Tools against COVID-19 and Hydrodynamic Cavitation-Based Extraction as a Method of Increasing Their Production [ May be a good prevention for COVID 19. ] Based on recent computational and experimental studies, hesperidin, a bioactive flavonoid abundant in citrus peel, stands out for its high binding affinity to the main cellular receptors of SARS-CoV-2, outperforming drugs already recommended for clinical trials. Thus, it is very promising for prophylaxis and treatment of COVID-19, along with other coexistent flavonoids such as naringin, which could help restraining the proinflammatory overreaction of the immune system. Controlled hydrodynamic cavitation processes showed the highest speed, effectiveness and efficiency in the integral and green aqueous extraction of flavonoids, essential oils and pectin from citrus peel waste. This study reviews the recent evidence about hesperidin as a promising molecule, and proposes a feasible and affordable process based on hydrodynamic cavitation for the integral aqueous extraction of citrus peel waste resulting in hesperidin-rich products, either aqueous extracts or pectin tablets. The uptake of this process on a relevant scale is urged, in order to achieve large-scale production and distribution of hesperidin-rich products.

Revisiting pharmacological potentials of Nigella sativa seed: a promising option for COVID-19 prevention and cure Nigella sativa seed and its active compounds have been historically recognized as an effective herbal panacea that can establish a balanced inflammatory response by suppressing chronic inflammation and promoting healthy immune response. The essential oil and other preparations of N. sativa seed have substantial therapeutic outcomes against immune disturbance, autophagy dysfunction, oxidative stress, ischemia, inflammation, in several COVID 19 comorbidities such as diabetes, cardiovascular disorders, Kawasaki-like diseases, and many bacterial and viral infections. Compelling evidence in the therapeutic efficiency of N. sativa along with the recent computational findings is strongly suggestive of combating emerged COVID 19 pandemic. This review was aimed at revisiting the pharmacological benefits of N. sativa seed and its active metabolites that may constitute a potential basis for developing a novel preventive and therapeutic strategy against COVID 19. Bioactive compounds of N. sativa seed, especially thymiquinone, a-hederin, and nigellidine, could be alternative and promising herbal drugs to combat COVID 19.

Thymoquinone: shield and sword against SARS-CoV-2 Since its emergence, the epidemic scale of the new coronavirus (SARS-CoV-2) has increased at an extraordinary rate. Governments, medical personnel, researchers, and companies work to the limits of their capabilities, in attempts to combat the virus. Companies are giving up current projects and chang- ing their activities to help with fighting the virus. In this difficult time, every piece of useful information is valuable. Here, we bring to the attention of the scientific and medical community thymoquinone (TQ), a substance mostly unknown to experts in Western countries, which holds the promise to help treat people infected with this novel virus by (1) by inhibiting its proliferation, (2) by killing it, (3) by killing the bacteria associated with pneumonia, (4) with its anti-inflammatory and (5) with its immuno- modulatory effect – perhaps acting synergistically, or even as a prophylactic remedy to prevent SARS- CoV-2 infection. However, due to its hydrophobicity, the systemic bioavailability of TQ is low. Nanocarriers targeting the lungs exist, and TQ has already been successfully used in nanomedicines targeting different organs except the lungs. Thus, there is not a long way to go. This is the challenge for nanomedicine. It was an anecdotal case report that stimulated the investigation of the therapeutic effect of TQ and the derivation of a mechanism for its dual antiviral action, applicable to COVID-19. Further- more, by exploiting the material published on the antiviral effect of TQ, we compared its antiviral mechanism with that of chloroquine (CQ) and hydroxychloroquine (HCQ). Our analysis indicates that the antiviral action of TQ is similar and most likely superior to that of CQ and HCQ, however, appar- ently without the adverse effects reported for CQ and HCQ. The broad antiviral spectrum and the mech- anism by which TQ presumably neutralizes the new virus justifies the hypothesis that TQ is effective in treating COVID-19.

Molecular docking, simulation and MM PBSA studies of nigella sativa compounds: a computational quest to identify potential natural antiviral for COVID 19 treatment Nigella sativa or black seed is used as a medicinal plant around the globe. Oil and seeds have a long tradition of folklore use in various medicinal and food systems. The conventional therapeutic use of Nigella sativa, in different ways, has been reported in several studies to treat different diseases includ- ing influenza, headache, hypertension, diabetes, inflammation, eczema, fever, cough, asthma, bron- chitis, and fever. Based on previously reported potential therapeutic uses of N. sativa compounds, and keeping in mind the dire need of time for the development of potent antiviral, a combined docking, ADMET properties calculation, molecular dynamics, and MM-PBSA approaches were applied in the cur- rent study to check the therapeutic potentials of N. sativa chief constituents against COVID-19. Additionally, MM-PBSA also affirms the docking results. Compound DTQ of the present study, if validated in wet lab experiments, could be used to treat COVID-19 and could serve as a lead in the future for development of more effective nat- ural antivirals against COVID-19.

Is hesperidin essential for prophylaxis and treatment of COVID-19 Infection Hesperidin is a classical herbal medicine used worldwide for a long time with an excellent safety profile. Hesperidin is a well-known herbal medication used as an antioxidant and anti-inflammatory agent. Available shreds of evidence support the promising use of hesperidin in prophylaxis and treatment of COVID 19. Hesperidin can block coronavirus from entering host cells through ACE2 receptors which can prevent the infection. Anti-viral activity of hesperidin might constitute a treatment option for COVID-19 through improving host cellular immunity against infection and its good anti-inflammatory activity may help in controlling cytokine storm. Hesperidin mixture with diosmin co-administrated with heparin protect against venous thromboembolism which may prevent disease progression. Based on that, hesperidin might be used as a meaningful prophylactic agent and a promising adjuvant treatment option against SARS-CoV-2 infection.

Benefits of hesperidin in central nervous system disorders: a review Citrus species contain significant amounts of flavonoids that possess antioxidant activities; furthermore, dietary citrus is not associated with adverse effects or cytotoxicity in healthy individuals. Hesperidin, which is an abundant flavanone glycoside in the peel of citrus fruits, possesses a variety of biological capabilities that include antioxidant and anti-inflammatory actions. Over the last few decades, many studies have been investigated the biological actions of hesperidin and its aglycone, hesperetin, as well as their underlying mechanisms. Due to the antioxidant effects of hesperidin and its derivatives, the cardioprotective and anti-cancer effects of these compounds have been widely reviewed.

Effects of glucosyl-hesperidin and physical training on body weight, plasma lipids, oxidative status and vascular reactivity of rats fed with high-fat diet The aim of the study was to evaluate the effects of supplementation with glucosyl hesperidin (GH), with or without physical training, on body weight, fat depot, glucose and plasma lipids, oxidative status and vascular function of rats fed with high-fat diet (HFD). Physical exercise partially decreased the body fat accumulation, decreased plasma levels of glucose and lipids and improved general oxidative status and endothelium-independent relaxation in mesenteric arteries of rats fed with HFD. GH exhibited benefits only in the oxidative status. However, GH given in association with physical exercise did not cause further changes in addition to those promoted by physical exercise. On the contrary, in exercised animals, GH prevented those changes elicited by physical training in plasma glucose and lipids, oxidative status and endothelium-independent relaxation.

Beneficial Effects of Citrus Flavonoids on Cardiovascular and Metabolic Health The intake of citrus flavonoids has been associated with improved cardiovascular outcomes. Although citrus flavonoids exerted multiple beneficial effects, their mechanisms of action are not completely established. In this review, we summarized recent findings and advances in understanding the mechanisms underlying the protective effects of citrus flavonoids against oxidative stress, inflammation, diabetes, dyslipidemia, endothelial dysfunction, and atherosclerosis. Further studies and clinical trials to assess the efficacy and to explore the underlying mechanism(s) of action of citrus flavonoids are recommended.

The Citrus Flavonoids Hesperidin and Naringin Do Not Affect Serum Cholesterol in Moderately Hypercholesterolemic Men and Women [ Citrus flavonoids also did not affect serum HDL-cholesterol and triglyceride concentrations. ] 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.

Citrus Polyphenol Hesperidin Stimulates Production of Nitric Oxide in Endothelial Cells while Improving Endothelial Function and Reducing Inflammatory Markers in Patients with Metabolic Syndrome Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption.

A novel polyphenol extract improves endothelial function and bioavailability An extract from sweet orange Polyphenolic compounds from citrus fruits, specifically hesperetin-7-O-rutinoside from orange peels, have gained increasing attention for their positive effects on cardiovascular and metabolic parameters. However, low solubility and complex microbial metabolism in the gut typically limit both applicability in foods and its bioavailability and resulting biological activity in humans. First, we elaborate on the influence of the gut microbiota on polyphenol bioavailability. Second, and as primary focus of this review, we describe results obtained with a novel formulation of hesperetin-7-O-rutinoside 2S. This novel formulation of hesperetin-7-O-rutinoside 2S, compared to a standard hesperetin-7-O-rutinoside (hesperidin) extract, showed superior bioavailability of the active polyphenols in a human cross-over pharmacokinetic study. The bioavailability is over 50 percent higher for the novel formulation. This increased bioavailability creates a great opportunity to induce stronger beneficial health effects as were found up to now with standard hesperidin extracts.

Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers Diastolic blood pressure (DBP) was significantly lower after 4 wk consumption of orange juice or CDH than after consumption of CDP (P = 0.02), whereas microvascular endothelium-related reactivity was not significantly affected when measured after an overnight fast. However, both orange juice and CDH ingestion significantly improved postprandial microvascular endothelial reactivity compared with CDP (P < 0.05) when measured at the peak of plasma hesperetin concentration.

Novel Lipidized Derivatives of the Bioflavonoid Hesperidin: Dermatological, Cosmetic and Chemopreventive Applications Hesperidin is one of the most important natural flavonoids, known for its antioxidant, anti-inflammatory, anti-mutagenic, and anti-hypertensive properties. Despite its various biological activities, hesperidin is rarely used in the dermo-cosmetic field because of its poor solubility in both water and oil phases that makes difficult formulation, distribution and bioavailability through the skin layers. Moreover, hesperidin is still underestimated in skin care products, and literature data on its stability into a topical formulation are not yet available. In this paper we report the synthesis of five different derivatives of hesperidin and their evaluation in terms of antioxidant, antifungal, antiproliferative, and apoptotic effects on human leukemic K562 cells. Preliminary antiproliferative effects were considered since hyper-proliferation is involved in several cutaneous problems particularly in the case of photo-exposition and environmental pollution. Esp4 and Esp5 were found to be more active in inhibiting K562 cell growth than parent hesperidin. Esp3 exhibited different biological properties, i.e., antioxidant activity in the absence of antiproliferative effects.

The effects of hesperetin on apoptosis induction and inhibition of cell proliferation in the prostate cancer PC3 cells Prostate cancer is the second leading cause of cancer-related deaths and the most common cancer diagnosed in men in the United States and Europe. Hesperetin, a member of the flavonoids with antioxidant property, is found in fruits such as oranges and red fruits. This study was undertaken to evaluate the effects of hesperetin on apoptosis induction and inhibition of cell proliferation in the prostate cancer PC3 cells. Conclusion: These results clearly show that hesperetin can lead to inhibition of PC3 cells proliferation.

Apigenin and Hesperidin Downregulate DNA Repair Genes in MCF-7 Breast Cancer Cells and Augment Doxorubicin Toxicity A number of studies have confirmed anti-tumor activity of flavonoids and their ability to enhance the effectiveness of classical anticancer drugs. The mechanism of this phenomenon is difficult to explain because of the ambivalent nature of these compounds. Many therapeutic properties of these compounds are attributed to their antioxidant activity; however, it is known that they can act as oxidants. The aim of this study was to assess the influence of apigenin and hesperidin on MCF-7 breast cancer cells with doxorubicin. The cytotoxic effect was determined using an MTT test and cell cycle analysis. To evaluate the possible interaction mechanism, reduced glutathione levels, as well as the DNA oxidative damage and the double strand breaks, were evaluated. Additionally, mRNA expression of genes related to DNA repair was assessed. It was demonstrated that flavonoids intensified the cytotoxic effect of doxorubicin despite flavonoids reduced oxidative damage caused by the drug. At the same time, the number of double strand breaks significantly increased and expression of tested genes was downregulated. In conclusion, both apigenin and hesperidin enhance the cytotoxic effects of doxorubicin on breast cancer cells, and this phenomenon occurs regardless of oxidative stress but is accompanied by disorders of DNA damage response mechanisms.

Hesperidin-triggered necrosis-like cell death in skin cancer cell line A431 might be prompted by ROS mediated alterations in mitochondrial membrane potential Skin cancer is one of the lethal causes of cancer related deaths around the globe and with limited drug options and the side effects associated with the currently used drugs; there is pressing need for identification of novel anticancer lead molecules. The aim of the present study was to evaluate the anticancer activity of hesperidin against skin carcinoma cell line A431 and to investigate the underlying mechanism. Additionally, hesperidin also prompted DNA damage in A431 cell line. Notably, hesperidin stimulated the cytochrome c release only and exhibited no effect on the expression of apoptosis-related protein levels such as caspase-3, caspase-8, and Apaf 1. Taken together, hesperidin induced A431 cells death displayed a cellular pattern characteristic of necrotic cell death but not of apoptosis.

P53 SENSITIZES HUMAN COLON CANCER CELLS TO HESPERIDIN THROUGH UPREGULATION OF BAX AND P21 Hesperidin, a flavonoid found mainly in citrus, was reported to inhibit growth and proliferation of several cancers, including colon cancer cells. However, the question does p53 tumor suppressor protein is required for the effect of hesperidin is not yet clarified. Hesperidin inhibits HCT-116 p53 and HCT116 p53 colon cancer cell proliferation after 24 hrs of treatment as indicated in a dose- dependent manner.

Cytotoxicity of dietary flavonoids on different human cancer types Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue‐specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment.

Chemopreventive effect of hesperidin, a citrus bioflavonoid in two stage skin carcinogenesis In conclusion, oral administration of hesperidin protected mice against chemical carcinogenesis by increasing antioxidant status, reducing DMBAbTPA induced lipid peroxidation and inflammatory response, and repressing of Rassf7, Nrf2, PARP and NF-kB levels.

Kinetics of Radical-Scavenging Activity of Hesperetin and Hesperidin and their Inhibitory Activity on COX-2 Expression In the concentration range 250-500 ÌM, hesperetin and hesperidin showed potent inhibition of LPS-induced expression of the COX-2 gene in RAW 264.7 cells, suggesting the anti-inflammatory activity of these compounds. The ability of hesperetin and hesperidin to suppress COX-2 gene expression may be a consequence of their antioxidant activity.

HESPERIDIN, A PLANT FLAVONOID ACCELERATED THE CUTANEOUS WOUND HEALING Together, treatment with hesperidin accelerate angiogenesis and vasculogenesis via up-regulation of VEGF-c, Ang-1/Tie-2, TGF-b and Smad-2/3 mRNA expression to enhance wound healing in chronic diabetic foot ulcers.

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