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1.
Int J Mol Sci ; 23(7)2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1785743

ABSTRACT

This study aimed at obtaining hesperidin (Hed) and hesperetin (Het) systems with HP-ß-CD by means of the solvent evaporation method. The produced systems were identified using infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, in silico docking and molecular dynamics studies were performed to assess the most preferable site of interactions between tested compounds and HP-ß-CD. The changes of physicochemical properties (solubility, dissolution rate, and permeability) were determined chromatographically. The impact of modification on biological activity was tested in an antioxidant study as well as with regards to inhibition of enzymes important in pathogenesis of neurodegenerative diseases. The results indicated improvement in solubility over 1000 and 2000 times for Hed and Het, respectively. Permeability studies revealed that Hed has difficulties in crossing biological membranes, in contrast with Het, which can be considered to be well absorbed. The improved physicochemical properties influenced the biological activity in a positive manner by the increase in inhibitory activity on the DPPH radical and cholinoesterases. To conclude the use of HP-ß-CD as a carrier in the formation of an amorphous inclusion complex seems to be a promising approach to improve the biological activity and bioavailability of Hed and Het.


Subject(s)
Hesperidin , 2-Hydroxypropyl-beta-cyclodextrin/chemistry , Biological Availability , Calorimetry, Differential Scanning , Hesperidin/pharmacology , Solubility , Spectroscopy, Fourier Transform Infrared/methods , X-Ray Diffraction
2.
Am J Chin Med ; 50(2): 351-369, 2022.
Article in English | MEDLINE | ID: covidwho-1723921

ABSTRACT

The development of anti-COVID-19 drugs has become the top priority since the outbreak of the epidemic, and Traditional Chinese medicine plays an important role in reducing mortality. Here, hesperidin and its glycosylation product, glucosyl hesperidin were selected to determine their antiviral activity against SARS-CoV-2 due to their structural specificity as reported. To be specific, their binding ability with ACE2, M, S, RBD and N proteins were verified with both in silico and wet lab methods, i.e., molecular docking and binding affinity tests, including biolayer interferometry assay (BLI) and isothermal titration calorimetry assay (ITC). Moreover, systematic pharmacological analysis was conducted to reveal their pharmacological mechanism in treating COVID-19. Finally, their antiviral activity against SARS-CoV-2 was determined in vitro in a biosafety level 3 (BSL3) laboratory. The results demonstrated their outstanding binding affinity with ACE2, M, S and RBD proteins, while showed barely unobserved binding with N protein, indicating their key roles in influencing the invasion and early replication phase of SARS-CoV-2. In addition, both hesperidin and glucosyl hesperidin were shown to have a great impact on immune, inflammation and virus infection induced by COVID-19 according to the systematic pharmacological analysis. Moreover, the IC50s of hesperidin and glucosyl hesperidin against SARS-CoV-2 were further determined (51.5 [Formula: see text]M and 5.5 mM, respectively) with cell-based in vitro assay, suggesting their great anti-SARS-CoV-2 activity. All in all, present research was the first to verify the binding ability of hesperidin and glucosyl hesperidin with SARS-CoV-2 proteins with both in silico and wet-lab methods and proposed the possibility of applying hesperidin and glucosyl hesperidin to treat COVID-19.


Subject(s)
COVID-19 , Hesperidin , Antiviral Agents/pharmacology , COVID-19/drug therapy , Computational Biology , Glucosides , Hesperidin/analogs & derivatives , Hesperidin/pharmacology , Humans , Molecular Docking Simulation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
3.
Nutrients ; 13(8)2021 Aug 16.
Article in English | MEDLINE | ID: covidwho-1360797

ABSTRACT

Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.


Subject(s)
COVID-19/drug therapy , Hesperidin/chemistry , Hesperidin/pharmacology , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/metabolism , COVID-19/virology , Cell Line, Tumor , Chlorocebus aethiops , Coronavirus Papain-Like Proteases/chemistry , Coronavirus Papain-Like Proteases/metabolism , Humans , Molecular Docking Simulation , SARS-CoV-2/metabolism , Serine Endopeptidases/chemistry , Serine Endopeptidases/drug effects , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
4.
Colloids Surf B Biointerfaces ; 203: 111724, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1157210

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus (COVID-19), is the virus responsible for over 69,613,607 million infections and over 1,582,966 deaths worldwide. All treatment measures and protocols were considered to be supportive only and not curative. During this current coronavirus pandemic, searching for pharmaceutical or traditional complementary and integrative medicine to assist with prevention, treatment, and recovery has been advantageous. These phytopharmaceuticals and nutraceuticals can be more economic, available, safe and lower side effects. This is in silico comparison study of ten phenolic antiviral agents against SARS-CoV-2, as well as isolation of the most active metabolite from natural sources. Zinc oxide nanoparticles (ZnO NPs) were also then prepared using these metabolite as a reducing agent. All tested compounds showed predicted anti-SARS-CoV-2 activity. Hesperidin showed the highest docking score, this leads us to isolate it from the orange peels and we confirmed its structure by conventenional spectroscopic analysis. In addition, synthesis of hesperidin zinc oxide nanoparticles was characterized by UV, IR, XRD and TEM. In vitro antiviral activity of hesperidin and ZnO NPs was evaluated against hepatitis A virus as an example of RNA viruses. However, ZnO NPs and hesperidin showed antiviral activity against HAV but ZnO NPs showed higher activity than hesperidin. Thus, hesperidin and its mediated ZnO nanoparticles are willing antiviral agents and further studies against SARS-CoV-2 are required to be used as a potential treatment.


Subject(s)
COVID-19 , Hesperidin , Nanoparticles , Zinc Oxide , Antiviral Agents/pharmacology , Computer Simulation , Hesperidin/pharmacology , Humans , SARS-CoV-2 , Zinc Oxide/pharmacology
5.
Phytomedicine ; 85: 153315, 2021 May.
Article in English | MEDLINE | ID: covidwho-752997

ABSTRACT

BACKGROUND: The traditional Chinese medicine (TCM) formula Qing-Fei-Pai-Du decoction (QFPDD) was the most widely used prescription in China's campaign to contain COVID-19, which has exhibited positive effects. However, the underlying mode of action is largely unknown. PURPOSE: A systems pharmacology strategy was proposed to investigate the mechanisms of QFPDD against COVID-19 from molecule, pathway and network levels. STUDY DESIGN AND METHODS: The systems pharmacological approach consisted of text mining, target prediction, data integration, network study, bioinformatics analysis, molecular docking, and pharmacological validation. Especially, we proposed a scoring method to measure the confidence of targets identified by prediction and text mining, while a novel scheme was used to identify important targets from 4 aspects. RESULTS: 623 high-confidence targets of QFPDD's 12 active compounds were identified, 88 of which were overlapped with genes affected by SARS-CoV-2 infection. These targets were found to be involved in biological processes related with the development of COVID-19, such as pattern recognition receptor signaling, interleukin signaling, cell growth and death, hemostasis, and injuries of the nervous, sensory, circulatory, and digestive systems. Comprehensive network and pathway analysis were used to identify 55 important targets, which regulated 5 functional modules corresponding to QFPDD's effects in immune regulation, anti-infection, anti-inflammation, and multi-organ protection, respectively. Four compounds (baicalin, glycyrrhizic acid, hesperidin, and hyperoside) and 7 targets (AKT1, TNF-α, IL6, PTGS2, HMOX1, IL10, and TP53) were key molecules related to QFPDD's effects. Molecular docking verified that QFPDD's compounds may bind to 6 host proteins that interact with SARS-CoV-2 proteins, further supported the anti-virus effect of QFPDD. At last, in intro experiments validated QFPDD's important effects, including the inhibition of IL6, CCL2, TNF-α, NF-κB, PTGS1/2, CYP1A1, CYP3A4 activity, the up-regulation of IL10 expression, and repressing platelet aggregation. CONCLUSION: This work illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation, and multi-organ protection. It may strengthen the understanding of QFPDD and facilitate more application of this formula in the campaign to SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , SARS-CoV-2/drug effects , Animals , Anti-Inflammatory Agents/pharmacology , COVID-19/drug therapy , Computational Biology , Flavonoids/pharmacology , Glycyrrhizic Acid/pharmacology , Hesperidin/pharmacology , Humans , Male , Medicine, Chinese Traditional , Mice , Molecular Docking Simulation , Quercetin/analogs & derivatives , Quercetin/pharmacology , RAW 264.7 Cells , Rabbits , Signal Transduction/drug effects
6.
Med Hypotheses ; 144: 109957, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-548595

ABSTRACT

SARS-CoV-2 or COVID-19 is representing the major global burden that implicated more than 4.7 million infected cases and 310 thousand deaths worldwide in less than 6 months. The prevalence of this pandemic disease is expected to rise every day. The challenge is to control its rapid spread meanwhile looking for a specific treatment to improve patient outcomes. 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. Herein, we discuss the possible prophylactic and treatment mechanisms of hesperidin based on previous and recent findings. 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.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , Hesperidin/therapeutic use , Pandemics/prevention & control , Phytotherapy , SARS-CoV-2/drug effects , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/drug effects , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/epidemiology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/prevention & control , Diosmin/administration & dosage , Diosmin/therapeutic use , Drug Therapy, Combination , Heparin/administration & dosage , Heparin/therapeutic use , Hesperidin/administration & dosage , Hesperidin/pharmacology , Humans , MAP Kinase Signaling System/drug effects , Receptors, Virus/drug effects , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
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