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1.
Food Environ Virol ; 14(2): 120-137, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1877972

ABSTRACT

The use of natural resources for the prevention and treatment of diseases considered fatal to humanity has evolved. Several medicinal plants have nutritional and pharmacological potential in the prevention and treatment of viral infections, among them, turmeric, which is recognized for its biological properties associated with curcuminoids, mainly represented by curcumin, and found mostly in rhizomes. The purpose of this review was to compile the pharmacological activities of curcumin and its analogs, aiming at stimulating their use as a therapeutic strategy to treat infections caused by RNA genome viruses. We revisited its historical application as an anti-inflammatory, antioxidant, and antiviral agent that combined with low toxicity, motivated research against viruses affecting the population for decades. Most findings concentrate particularly on arboviruses, HIV, and the recent SARS-CoV-2. As one of the main conclusions, associating curcuminoids with nanomaterials increases solubility, bioavailability, and antiviral effects, characterized by blocking the entry of the virus into the cell or by inhibiting key enzymes in viral replication and transcription.


Subject(s)
COVID-19 , Curcumin , Antiviral Agents/pharmacology , COVID-19/drug therapy , Curcumin/pharmacology , Diarylheptanoids , Humans , RNA , SARS-CoV-2
2.
ACS Appl Bio Mater ; 5(2): 483-491, 2022 02 21.
Article in English | MEDLINE | ID: covidwho-1805546

ABSTRACT

Interleukin-mediated deep cytokine storm, an aggressive inflammatory response to SARS-CoV-2 virus infection in COVID-19 patients, is correlated directly with lung injury, multi-organ failure, and poor prognosis of severe COVID-19 patients. Curcumin (CUR), a phenolic antioxidant compound obtained from turmeric (Curcuma longa L.), is well-known for its strong anti-inflammatory activity. However, its in vivo efficacy is constrained due to poor bioavailability. Herein, we report that CUR-encapsulated polysaccharide nanoparticles (CUR-PS-NPs) potently inhibit the release of cytokines, chemokines, and growth factors associated with damage of SARS-CoV-2 spike protein (CoV2-SP)-stimulated liver Huh7.5 and lung A549 epithelial cells. Treatment with CUR-PS-NPs effectively attenuated the interaction of ACE2 and CoV2-SP. The effects of CUR-PS-NPs were linked to reduced NF-κB/MAPK signaling which in turn decreased CoV2-SP-mediated phosphorylation of p38 MAPK, p42/44 MAPK, and p65/NF-κB as well as nuclear p65/NF-κB expression. The findings of the study strongly indicate that organic NPs of CUR can be used to control hyper-inflammatory responses and prevent lung and liver injuries associated with CoV2-SP-mediated cytokine storm.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Curcumin/pharmacology , Cytokine Release Syndrome/prevention & control , MAP Kinase Signaling System/drug effects , NF-kappa B/metabolism , Nanoparticles/chemistry , Signal Transduction/drug effects , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Anti-Inflammatory Agents/pharmacokinetics , Cell Survival/drug effects , Chemokines/biosynthesis , Curcumin/chemistry , Curcumin/pharmacokinetics , Cytokines/biosynthesis , Humans , Intercellular Signaling Peptides and Proteins/biosynthesis , Phosphorylation , Spike Glycoprotein, Coronavirus/physiology
3.
Comput Biol Med ; 146: 105552, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1803808

ABSTRACT

BACKGROUND: Omicron (B.1.1.529), a variant of SARS-CoV-2 is currently spreading globally as a dominant strain. Due to multiple mutations at its Spike protein, including 15 amino acid substitutions at the receptor binding domain (RBD), Omicron is a variant of concern (VOC) and capable of escaping vaccine generated immunity. So far, no specific treatment regime is suggested for this VOC. METHODS: The three-dimensional structure of the Spike RBD domain of Omicron variant was constructed by incorporating 15 amino acid substitutions to the Native Spike (S) structure and structural changes were compared that of the Native S. Seven phytochemicals namely Allicin, Capsaicin, Cinnamaldehyde, Curcumin, Gingerol, Piperine, and Zingeberene were docked with Omicron S protein and Omicron S-hACE2 complex. Further, molecular dynamic simulation was performed between Crcumin and Omicron S protein to evaluate the structural stability of the complex in the physiological environment and compared with that of the control drug Chloroquine. RESULTS: Curcumin, among seven phytochemicals, was found to have the most substantial inhibitory potential with Omicron S protein. Further, it was found that curcumin could disrupt the Omicron S-hACE2 complex. The molecular dynamic simulation demonstrated that Curcumin could form a stable structure with Omicron S in the physiological environment. CONCLUSION: To conclude, Curcumin can be considered as a potential therapeutic agent against the highly infectious Omicron variant of SARS-CoV-2.


Subject(s)
COVID-19 , Curcumin , COVID-19/drug therapy , Curcumin/pharmacology , Humans , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/metabolism
4.
ACS Appl Mater Interfaces ; 14(16): 18989-19001, 2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1795857

ABSTRACT

Antibacterial air filtration membranes are essential for personal protection during the pandemic of coronavirus disease 2019 (COVID-19). However, high-efficiency filtration with low pressure drop and effective antibiosis is difficult to achieve. To solve this problem, an innovative electrospinning system with low binding energy and high conductivity was built to enhance the jet splitting, and a fluffy nanofibrous membrane containing numerous ultrafine nanofibers and large quantities of antibacterial agents was achieved, which was fabricated by electrospinning polyamide 6 (PA6), poly(vinyl pyrrolidone) (PVP), chitosan (CS), and curcumin (Cur). The filtration efficiency for 0.3 µm NaCl particles was 99.83%, the pressure drop was 54 Pa, and the quality factor (QF) was up to 0.118 Pa-1. CS and Cur synergistically enhanced the antibacterial performance; the bacteriostatic rates against Escherichia coli and Staphylococcus aureus were 99.5 and 98.9%, respectively. This work will largely promote the application of natural antibacterial agents in the development of high-efficiency, low-resistance air filters for personal protection by manufacturing ultrafine nanofibers with enhanced antibiosis.


Subject(s)
Air Filters , COVID-19 , Chitosan , Curcumin , Nanofibers , Anti-Bacterial Agents/pharmacology , COVID-19/drug therapy , Chitosan/pharmacology , Curcumin/pharmacology , Escherichia coli , Filtration , Humans , Nanofibers/chemistry
5.
Drug Discov Ther ; 16(1): 14-22, 2022.
Article in English | MEDLINE | ID: covidwho-1737267

ABSTRACT

Accumulating evidence has been reported regarding the effect of curcumin as a dietary antiviral on patients with COVID-19; however, findings are controversial. Our systematic review aimed to evaluate the effects of curcumin in patients with COVID-19. Electronic databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar) were systematically searched to identify only randomized clinical trials (RCTs) that assessed curcumin in patients with COVID-19 from inception to September 23, 2021 relevant keywords. The Cochrane risk-of-bias tool for randomized trials was used to evaluate the risk of bias. After a critical review of 1,098 search hits, only six RCTs were selected for discussion. A total of 480 patients were included, with 240 amongst the curcumin groups and 240 in the control group. The lymphocyte count was significantly higher in the curcumin group compared to the placebo group. Curcumin was found to decrease the number of T-helper 17 cells, downregulate T-helper-17 cell-related factors, reduce levels of T-helper-17 cell-related cytokines, yet increase the gene expression of Treg transcription factor forkhead box P3 (FOXP3), and decrease T-Box transcription factor 21 (TBX21). Our review revealed that curcumin might have a positive effect on relieving COVID-19 related inflammatory response due to its powerful immune-modulatory effects on cytokines production, T-cell responses, and gene expression. These findings suggest that curcumin confers clinical benefits in patients with COVID-19. However, due to the limited number of the included studies, further high-quality studies are needed to establish the clinical efficacy of the curcumin.


Subject(s)
COVID-19 , Curcumin , COVID-19/drug therapy , Curcumin/pharmacology , Curcumin/therapeutic use , Dietary Supplements , Humans , Randomized Controlled Trials as Topic , SARS-CoV-2
6.
Int J Mol Sci ; 23(4)2022 Feb 10.
Article in English | MEDLINE | ID: covidwho-1715394

ABSTRACT

Tuberculosis (TB) is one of the ten leading causes of death worldwide. Patients with TB have been observed to suffer from depression and anxiety linked to social variables. Previous experiments found that the substantial pulmonary inflammation associated with TB causes neuroinflammation, neuronal death, and behavioral impairments in the absence of brain infection. Curcumin (CUR) is a natural product with antioxidant, anti-inflammatory and antibacterial activities. In this work, we evaluated the CUR effect on the growth control of mycobacteria in the lungs and the anti-inflammatory effect in the brain using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive mycobacteria (strain H37Rv). The results have shown that CUR decreased lung bacilli load and pneumonia of infected animals. Finally, CUR significantly decreased neuroinflammation (expression of TNFα, IFNγ and IL12) and slightly increased the levels of nuclear factor erythroid 2-related to factor 2 (Nrf2) and the brain-derived neurotrophic factor (BDNF) levels, improving behavioral status. These results suggest that CUR has a bactericidal effect and can control pulmonary mycobacterial infection and reduce neuroinflammation. It seems that CUR has a promising potential as adjuvant therapy in TB treatment.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antitubercular Agents/pharmacology , Brain/microbiology , Curcumin/pharmacology , Lung/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis/drug therapy , Animals , Brain/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Disease Models, Animal , Inflammation/drug therapy , Inflammation/metabolism , Lung/metabolism , Male , Mice , Mice, Inbred BALB C , Mycobacterium tuberculosis/drug effects , Tuberculosis/metabolism , Tuberculosis, Pulmonary/metabolism
7.
Comput Biol Chem ; 98: 107657, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1709409

ABSTRACT

The novel coronavirus disease (COVID-19) is a highly contagious disease caused by the SARS-CoV-2 virus, leading severe acute respiratory syndrome in patients. Although various antiviral drugs and their combinations have been tried so far against SARS-CoV-2 and they have shown some effectiveness, there is still a need for safe and cost-effective binding inhibitors in the fight against COVID-19. Therefore, phytochemicals in nature can be a quick solution due to their wide therapeutic spectrum and strong antiviral, anti-inflammatory, and antioxidant properties. In this context, the low toxicity, and high pharmacokinetic properties of curcumin, which is a natural phytochemical, as well as the easy synthesizing of its derivatives reveal the need for investigation of its various derivatives as inhibitors against coronaviruses. The present study focused on curcumin derivatives with reliable ADME profile and high molecular binding potency to different SARS-CoV-2 target enzymes (3CLPro, PLpro, NSP7/8/12, NSP7/8/12 +RNA, NSP15, NSP16, Spike, Spike+ACE). In the molecular docking studies, the best binding scores for the 22 proposed curcumin derivatives were obtained for the PLpro protein. Furthermore, MD simulations were performed for high-affinity ligand-PLpro protein complexes and subsequently, Lys157, Glu161, Asp164, Arg166, Glu167, Met208, Pro247, Pro248, Tyr264, Tyr273 and Asp302 residues of PLpro was determined to play key role for ligand binding by Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis. The results of the study promise that the proposed curcumin derivatives can be potent inhibitors against SARS-CoV-2 and be converted into pharmaceutical drugs. It is also expected that the findings may provide guiding insights to future design studies for synthesizing different antiviral derivatives of phytochemicals.


Subject(s)
COVID-19 , Curcumin , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Curcumin/pharmacology , Humans , Ligands , Molecular Docking Simulation , Phytochemicals , SARS-CoV-2
8.
Int J Mol Sci ; 23(3)2022 Feb 04.
Article in English | MEDLINE | ID: covidwho-1674669

ABSTRACT

Recently, the world has been witnessing a global pandemic with no effective therapeutics yet, while cancer continues to be a major disease claiming many lives. The natural compound curcumin is bestowed with multiple medicinal applications in addition to demonstrating antiviral and anticancer activities. In order to elucidate the impact of curcumin on COVID-19 and cancer, the current investigation has adapted several computational techniques to unfold its possible inhibitory activity. Accordingly, curcumin and similar compounds and analogues were retrieved and assessed for their binding affinities at the binding pocket of SARS-CoV-2 main protease and DDX3. The best binding pose was escalated to molecular dynamics simulation (MDS) studies to assess the time dependent stability. Our findings have rendered one compound that has demonstrated good molecular dock score complemented by key residue interactions and have shown stable MDS results inferred by root mean square deviation (RMSD), radius of gyration (Rg), binding mode, hydrogen bond interactions, and interaction energy. Essential dynamics results have shown that the systemadapts minimum energy conformation to attain a stable state. The discovered compound (curA) could act as plausible inhibitor against SARS-CoV-2 and DDX3. Furthermore, curA could serve as a chemical scaffold for designing and developing new compounds.


Subject(s)
Curcumin/analogs & derivatives , Curcumin/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , COVID-19/drug therapy , Computational Biology/methods , Drug Evaluation, Preclinical/methods , Humans , Molecular Docking Simulation/methods , Molecular Dynamics Simulation , Neoplasms/drug therapy , Protease Inhibitors/pharmacology , Protein Binding/drug effects , SARS-CoV-2/pathogenicity
9.
J Photochem Photobiol B ; 227: 112378, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1654818

ABSTRACT

In a recent study, we showed that pulsed blue light (PBL) inactivates as much as 52.3% of human beta coronavirus HCoV-OC43, a surrogate of SARS-CoV-2, and one of the major strains of viruses responsible for the annual epidemic of the common cold. Since curcumin and saliva are similarly antiviral and curcumin acts as blue light photosensitizer, we used Qubit fluorometry and WarmStart RT-LAMP assays to study the effect of combining 405 nm, 410 nm, 425 nm or 450 nm wavelengths of PBL with curcumin, saliva or a combination of curcumin and saliva against human beta coronavirus HCoV-OC43. The results showed that PBL, curcumin and saliva independently and collectively inactivate HCoV-OC43. Without saliva or curcumin supplementation 21.6 J/cm2 PBL reduced HCoV-OC43 RNA concentration a maximum of 32.8% (log10 = 2.13). Saliva supplementation alone inactivated the virus, reducing its RNA concentration by 61% (log10 = 2.23); with irradiation the reduction was as much as 79.1%. Curcumin supplementation alone decreased viral RNA 71.1%, and a maximum of 87.8% with irradiation. The combination of saliva and curcumin reduced viral RNA to 83.1% and decreased the RNA up to 90.2% with irradiation. The reduced levels could not be detected with qPCR. These findings show that PBL in the range of 405 nm to 450 nm wavelength is antiviral against human coronavirus HCoV-OC43, a surrogate of the COVID-19 virus. Further, it shows that with curcumin as a photosensitizer, it is possible to photodynamically inactivate the virus beyond qPCR detectable level using PBL. Since HCoV-OC43 is of the same beta coronavirus family as SARS-CoV-2, has the same genomic size, and is often used as its surrogate, these findings heighten the prospect of similarly inactivating novel coronavirus SARS-CoV-2, the virus responsible for COVID-19 pandemic.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/therapy , Curcumin/pharmacology , Photosensitizing Agents/pharmacology , SARS-CoV-2/drug effects , Saliva/chemistry , Combined Modality Therapy , Coronavirus OC43, Human , Humans , Light , Photochemical Processes , Photochemotherapy , RNA, Viral
10.
Graefes Arch Clin Exp Ophthalmol ; 260(5): 1457-1473, 2022 May.
Article in English | MEDLINE | ID: covidwho-1616130

ABSTRACT

PURPOSE: To review the role of curcumin in retinal diseases, COVID era, modification of the molecule to improve bioavailability and its future scope. METHODS: PubMed and MEDLINE searches were pertaining to curcumin, properties of curcumin, curcumin in retinal diseases, curcumin in diabetic retinopathy, curcumin in age-related macular degeneration, curcumin in retinal and choroidal diseases, curcumin in retinitis pigmentosa, curcumin in retinal ischemia reperfusion injury, curcumin in proliferative vitreoretinopathy and curcumin in current COVID era. RESULTS: In experimental models, curcumin showed its pleiotropic effects in retinal diseases like diabetic retinopathy by increasing anti-oxidant enzymes, upregulating HO-1, nrf2 and reducing or inhibiting inflammatory mediators, growth factors and by inhibiting proliferation and migration of retinal endothelial cells in a dose-dependent manner in HRPC, HREC and ARPE-19 cells. In age-related macular degeneration, curcumin acts by reducing ROS and inhibiting apoptosis inducing proteins and cellular inflammatory genes and upregulating HO-1, thioredoxin and NQO1. In retinitis pigmentosa, curcumin has been shown to delay structural defects of P23H gene in P23H-rhodopsin transgenic rats. In proliferative vitreoretinopathy, curcumin inhibited the action of EGF in a dose- and time-dependent manner. In retinal ischemia reperfusion injury, curcumin downregulates IL-17, IL-23, NFKB, STAT-3, MCP-1 and JNK. In retinoblastoma, curcumin inhibits proliferation, migration and apoptosis of RBY79 and SO-RB50. Curcumin has already proven its efficacy in inhibiting viral replication, coagulation and cytokine storm in COVID era. CONCLUSION: Curcumin is an easily available spice used traditionally in Indian cooking. The benefits of curcumin are manifold, and large randomized controlled trials are required to study its effects not only in treating retinal diseases in humans but in their prevention too.


Subject(s)
COVID-19 , Curcumin , Diabetic Retinopathy , Macular Degeneration , Reperfusion Injury , Retinal Diseases , Retinal Neoplasms , Retinitis Pigmentosa , Vitreoretinopathy, Proliferative , Animals , Curcumin/pharmacology , Endothelial Cells , Humans , Rats , Reperfusion Injury/prevention & control , Retinal Diseases/drug therapy
11.
Nutrients ; 14(2)2022 Jan 07.
Article in English | MEDLINE | ID: covidwho-1613925

ABSTRACT

Despite the ongoing vaccination efforts, there is still an urgent need for safe and effective treatments to help curb the debilitating effects of COVID-19 disease. This systematic review aimed to investigate the efficacy of supplemental curcumin treatment on clinical outcomes and inflammation-related biomarker profiles in COVID-19 patients. We searched PubMed, Scopus, Web of Science, EMBASE, ProQuest, and Ovid databases up to 30 June 2021 to find studies that assessed the effects of curcumin-related compounds in mild to severe COVID-19 patients. Six studies were identified which showed that curcumin supplementation led to a significant decrease in common symptoms, duration of hospitalization and deaths. In addition, all of these studies showed that the intervention led to amelioration of cytokine storm effects thought to be a driving force in severe COVID-19 cases. This was seen as a significant (p < 0.05) decrease in proinflammatory cytokines such as IL1ß and IL6, with a concomitant significant (p < 0.05) increase in anti-inflammatory cytokines, including IL-10, IL-35 and TGF-α. Taken together, these findings suggested that curcumin exerts its beneficial effects through at least partial restoration of pro-inflammatory/anti-inflammatory balance. In conclusion, curcumin supplementation may offer an efficacious and safe option for improving COVID-19 disease outcomes. We highlight the point that future clinical studies of COVID-19 disease should employ larger cohorts of patients in different clinical settings with standardized preparations of curcumin-related compounds.


Subject(s)
COVID-19/drug therapy , Curcumin/administration & dosage , Dietary Supplements , Hospitalization , Phytotherapy/methods , Curcumin/pharmacology , Cytokines/metabolism , Female , Humans , Inflammation Mediators/metabolism , Interleukin-10/metabolism , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Interleukins/metabolism , Male , Patient Acuity , Transforming Growth Factor alpha/metabolism , Treatment Outcome
12.
Int J Biol Macromol ; 198: 101-110, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1587672

ABSTRACT

Respiratory infected by COVID-19 represents a major global health problem at moment even after recovery from virus corona. Since, the lung lesions for infected patients are still sufferings from acute respiratory distress syndrome including alveolar septal edema, pneumonia, hyperplasia, and hyaline membranes Therefore, there is an urgent need to identify additional candidates having ability to overcome inflammatory process and can enhance efficacy in the treatment of COVID-19. The polypenolic extracts were integrated into moeties of bovine serum albumin (BSA) and then were coated by chitosan as a mucoadhesion polymer. The results of interleukin-6, and c-reactive protein showed significant reduction in group treated by Encap. SIL + CUR (64 ± 0.8 Pg/µL & 6 ± 0.5 µg/µL) compared to group treated by Cham. + CUR (102 ± 0.8 Pg/µL & 7 ± 0.5 µg/µL) respectively and free capsules (with no any drug inside) (148 ± 0.6 Pg/µL & 10 ± 0.6 µg/µL) respectively. Histopathology profile was improved completely. Additionally, encapsulating silymarin showed anti-viral activity in vitro COVID-19 experiment. It can be summarized that muco-inhalable delivery system (MIDS) loaded by silymarin can be used to overcome inflammation induced by oleic acid and to overcome COVID-19.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Curcumin/pharmacology , Lung Injury/drug therapy , Nanoparticles/chemistry , Silymarin/pharmacology , Administration, Inhalation , Animals , Anti-Inflammatory Agents/administration & dosage , Antiviral Agents/administration & dosage , C-Reactive Protein/metabolism , Chamomile/chemistry , Chitosan/chemistry , Chlorocebus aethiops , Curcumin/administration & dosage , Drug Delivery Systems/methods , Flavonoids/analysis , Flavonoids/chemistry , Interleukin-6/metabolism , Lung Injury/blood , Lung Injury/chemically induced , Lung Injury/pathology , Male , Mice , Milk Thistle/chemistry , Nanoparticles/administration & dosage , Oleic Acid/toxicity , Silymarin/administration & dosage , Vero Cells , Viral Plaque Assay
13.
Molecules ; 26(22)2021 Nov 16.
Article in English | MEDLINE | ID: covidwho-1524084

ABSTRACT

Due to the scarcity of therapeutic approaches for COVID-19, we investigated the antiviral and anti-inflammatory properties of curcumin against SARS-CoV-2 using in vitro models. The cytotoxicity of curcumin was evaluated using MTT assay in Vero E6 cells. The antiviral activity of this compound against SARS-CoV-2 was evaluated using four treatment strategies (i. pre-post infection treatment, ii. co-treatment, iii. pre-infection, and iv. post-infection). The D614G strain and Delta variant of SARS-CoV-2 were used, and the viral titer was quantified by plaque assay. The anti-inflammatory effect was evaluated in peripheral blood mononuclear cells (PBMCs) using qPCR and ELISA. By pre-post infection treatment, Curcumin (10 µg/mL) exhibited antiviral effect of 99% and 99.8% against DG614 strain and Delta variant, respectively. Curcumin also inhibited D614G strain by pre-infection and post-infection treatment. In addition, curcumin showed a virucidal effect against D614G strain and Delta variant. Finally, the pro-inflammatory cytokines (IL-1ß, IL-6, and IL-8) released by PBMCs triggered by SARS-CoV-2 were decreased after treatment with curcumin. Our results suggest that curcumin affects the SARS-CoV-2 replicative cycle and exhibits virucidal effect with a variant/strain independent antiviral effect and immune-modulatory properties. This is the first study that showed a combined (antiviral/anti-inflammatory) effect of curcumin during SARS-CoV-2 infection. However, additional studies are required to define its use as a treatment for the COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Curcumin/pharmacology , SARS-CoV-2/drug effects , Animals , Anti-Inflammatory Agents/pharmacology , COVID-19/prevention & control , Cell Survival/drug effects , Chlorocebus aethiops , Cytokines/genetics , Cytokines/metabolism , Healthy Volunteers , Humans , Leukocytes, Mononuclear/drug effects , Vero Cells
14.
Drug Des Devel Ther ; 15: 4503-4525, 2021.
Article in English | MEDLINE | ID: covidwho-1511886

ABSTRACT

Curcumin is a natural compound with great potential for disease treatment. A large number of studies have proved that curcumin has a variety of biological activities, among which anti-inflammatory effect is a significant feature of it. Inflammation is a complex and pervasive physiological and pathological process. The physiological and pathological mechanisms of inflammatory bowel disease, psoriasis, atherosclerosis, COVID-19 and other research focus diseases are not clear yet, and they are considered to be related to inflammation. The anti-inflammatory effect of curcumin can effectively improve the symptoms of these diseases and is expected to be a candidate drug for the treatment of related diseases. This paper mainly reviews the anti-inflammatory effect of curcumin, the inflammatory pathological mechanism of related diseases, the regulatory effect of curcumin on these, and the latest research results on the improvement of curcumin pharmacokinetics. It is beneficial to the further study of curcumin and provides new ideas and insights for the development of curcumin anti-inflammatory preparations.


Subject(s)
Anti-Inflammatory Agents/pharmacology , COVID-19/drug therapy , Curcumin/pharmacology , Inflammation/drug therapy , SARS-CoV-2 , Animals , Atherosclerosis/drug therapy , Curcumin/therapeutic use , Depression/drug therapy , Humans
16.
PLoS One ; 16(6): e0253489, 2021.
Article in English | MEDLINE | ID: covidwho-1388925

ABSTRACT

In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3'-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3,3'-digallate at 25 µg/ml and curcumin above 10 µg/ml concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at the same time its activity in both cell-free and cell-based assays. Our study also demonstrates that brazilin and theaflavin-3,3'-digallate, and to a still greater extent, curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and cell-based assays. Similar pattern was observed with cathepsin L, although only theaflavin-3,3'-digallate showed a modest diminution of cathepsin L expression at protein level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. In conclusion, this study demonstrates pleiotropic anti-SARS-CoV-2 efficacy of specific polyphenols and their prospects for further scientific and clinical investigations.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/prevention & control , Polyphenols/pharmacology , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects , A549 Cells , Benzopyrans/pharmacology , Biflavonoids/pharmacology , COVID-19/virology , Catechin/analogs & derivatives , Catechin/pharmacology , Cell Survival/drug effects , Curcumin/pharmacology , Humans , Protein Binding/drug effects , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Virion/drug effects , Virion/metabolism , Virion/physiology , Virus Attachment/drug effects
17.
Int J Nanomedicine ; 16: 5053-5064, 2021.
Article in English | MEDLINE | ID: covidwho-1362162

ABSTRACT

BACKGROUND: High levels of oxidants, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are typical characteristics of an inflammatory microenvironment and are closely associated with a various inflammatory pathologies, eg, cancer, diabetes, atherosclerosis, and neurodegenerative diseases. Therefore, the delivery of anti-inflammatory drugs by oxidation-responsive smart systems would be an efficient anti-inflammatory strategy that benefits from the selective drug release in an inflammatory site, a lower treatment dose, and minimizes side effects. PURPOSE: In this study, we present the feasibility of an oxidation-sensitive PEGylated alternating polyester, methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), as novel nanocarrier for curcumin (CUR), and explore the application in anti-inflammatory therapy. METHODS: The copolymers used were obtained by combining a click reaction and a ring-opening-polymerization method. CUR was loaded by self-assembly. The in vitro drug release, cytotoxicity toward RAW 264.7 cells and cellular uptake were investigated. Furthermore, the anti-inflammatory effects of CUR-loaded polymeric nanoparticles (NPs-CUR) were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and tested in a murine model of ankle inflammation. RESULTS: Fast drug release from NPs-CUR was observed in trigger of 1 mM H2O2 in PBS. Compared with NPs and free drugs, the significant anti-inflammatory potential of NPs-CUR was proven in activated RAW 264.7 cells by inhibiting the production of TNF-α, IL-1ß, and IL-6 and increasing the level of an anti-inflammatory cytokine IL-10. Finally, a local injection of NPs-CUR at a dose of 0.25 mg/kg suppressed the acute ankle inflammatory response in mice by histological observation and further reduced the expression of pro-inflammatory cytokines in the affected ankle joints compared to that of free CUR. CONCLUSION: Both the significant in vitro and in vivo anti-inflammatory results indicated that our oxidation responsive polymeric nanoparticles are promising drug delivery systems for anti-inflammatory therapy.


Subject(s)
Nanoparticles , Polyesters/chemistry , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Curcumin/pharmacology , Drug Carriers , Drug Delivery Systems , Drug Liberation , Hydrogen Peroxide , Mice , Pharmaceutical Preparations , Polyethylene Glycols
18.
Adv Exp Med Biol ; 1327: 197-204, 2021.
Article in English | MEDLINE | ID: covidwho-1316249

ABSTRACT

COVID-19 is now pandemic throughout the world, and scientists are searching for effective therapies to prevent or treat the disease. The combination of curcumin and piperine is a potential option for the management of COVID-19 based on several mechanisms including antiviral, anti-inflammatory, immunomodulatory, antifibrotic, and antioxidant effects. Here, we describe the probable mechanism of curcumin-piperine against COVID-19. Administration of curcumin-piperine combination appears as a potential strategy to counterbalance the pathophysiological features of COVID-19 including inflammation. The optimal dose and duration of curcumin-piperine supplementation should be determined in the future.


Subject(s)
COVID-19 , Curcumin , Alkaloids , Benzodioxoles , Curcumin/pharmacology , Humans , Piperidines , Polyunsaturated Alkamides/pharmacology , SARS-CoV-2
19.
Biomed Pharmacother ; 141: 111888, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1293595

ABSTRACT

Curcumin, isolated from Curcuma longa L., is a fat-soluble natural compound that can be obtained from ginger plant tuber roots, which accumulative evidences have demonstrated that it can resist viral and microbial infection and has anti-tumor, reduction of blood lipid and blood glucose, antioxidant and removal of free radicals, and is active against numerous disorders various chronic diseases including cardiovascular, pulmonary, neurological and autoimmune diseases. In this article is highlighted the recent evidence of curcuminoids applied in sevral aspects of medical problem particular in COVID-19 pandemics. We have searched several literature databases including MEDLINE (PubMed), EMBASE, the Web of Science, Cochrane Library, Google Scholar, and the ClinicalTrials.gov website via using curcumin and medicinal properties as a keyword. All studies published from the time when the database was established to May 2021 was retrieved. This review article summarizes the growing confirmation for the mechanisms related to curcumin's physiological and pharmacological effects with related target proteins interaction via molecular docking. The purpose is to provide deeper insight and understandings of curcumin's medicinal value in the discovery and development of new drugs. Curcumin could be used in the prevention or therapy of cardiovascular disease, respiratory diseases, cancer, neurodegeneration, infection, and inflammation based on cellular biochemical, physiological regulation, infection suppression and immunomodulation.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antineoplastic Agents/therapeutic use , Antioxidants/therapeutic use , Curcumin/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Antioxidants/metabolism , Antioxidants/pharmacology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/metabolism , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/metabolism , Curcumin/metabolism , Curcumin/pharmacology , Humans , Neoplasms/drug therapy , Neoplasms/metabolism , Protein Structure, Secondary
20.
J Nutr Biochem ; 97: 108787, 2021 11.
Article in English | MEDLINE | ID: covidwho-1253236

ABSTRACT

The outbreak of mysterious pneumonia at the end of 2019 is associated with widespread research interest worldwide. The coronavirus disease-19 (COVID-19) targets multiple organs through inflammatory, immune, and redox mechanisms, and no effective drug for its prophylaxis or treatment has been identified until now. The use of dietary bioactive compounds, such as phenolic compounds (PC), has emerged as a putative nutritional or therapeutic adjunct approach for COVID-19. In the present study, scientific data on the mechanisms underlying the bioactivity of PC and their usefulness in COVID-19 mitigation are reviewed. In addition, antioxidant, antiviral, anti-inflammatory, and immunomodulatory effects of dietary PC are studied. Moreover, the implications of digestion on the putative benefits of dietary PC against COVID-19 are presented by addressing the bioavailability and biotransformation of PC by the gut microbiota. Lastly, safety issues and possible drug interactions of PC and their implications in COVID-19 therapeutics are discussed.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/therapeutic use , COVID-19/therapy , Dietary Supplements , Gastrointestinal Microbiome , Phenols/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/pharmacokinetics , Antioxidants/pharmacology , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Biological Availability , Curcumin/pharmacokinetics , Curcumin/pharmacology , Curcumin/therapeutic use , Dietary Supplements/analysis , Gastrointestinal Microbiome/drug effects , Humans , Immunologic Factors/pharmacokinetics , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Phenols/pharmacokinetics , Phenols/pharmacology , Quercetin/pharmacokinetics , Quercetin/pharmacology , Quercetin/therapeutic use , Resveratrol/pharmacokinetics , Resveratrol/pharmacology , Resveratrol/therapeutic use , SARS-CoV-2/drug effects
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