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1.
Nutrients ; 13(12)2021 Dec 16.
Article in English | MEDLINE | ID: covidwho-1580557

ABSTRACT

The excessive synthesis of interleukin-6 (IL-6) is related to cytokine storm in COVID-19 patients. Moreover, blocking IL-6 has been suggested as a treatment strategy for inflammatory diseases such as sepsis. Sepsis is a severe systemic inflammatory response syndrome with high mortality. In the present study, we investigated the anti-inflammatory and anti-septic effects and the underlying mechanisms of Dracocephalum moldavica ethanol extract (DMEE) on lipopolysaccharide (LPS)-induced inflammatory stimulation in RAW 264.7 macrophages along with septic mouse models. We found that DMEE suppressed the release of inflammatory mediators NO and PGE2 and inhibited both the mRNA and protein expression levels of iNOS and COX-2, respectively. In addition, DMEE reduced the release of proinflammatory cytokines, mainly IL-6 and IL-1ß, in RAW 264.7 cells by inhibiting the phosphorylation of JNK, ERK and p65. Furthermore, treatment with DMEE increased the survival rate and decreased the level of IL-6 in plasma in LPS-induced septic shock mice. Our findings suggest that DMEE elicits an anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophages and an anti-septic effect on septic mouse model through the inhibition of the ERK/JNK/NF-κB signaling cascades and production of IL-6.


Subject(s)
Interleukin-6/metabolism , Lamiaceae/chemistry , Lipopolysaccharides/toxicity , MAP Kinase Signaling System/drug effects , Plant Extracts/pharmacology , Transcription Factor RelA/metabolism , Animals , Ethanol/chemistry , Extracellular Signal-Regulated MAP Kinases/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , MAP Kinase Kinase 4/metabolism , Male , Mice , Plant Extracts/chemistry , RAW 264.7 Cells
2.
Int J Mol Sci ; 22(24)2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1572494

ABSTRACT

Low density polyethylene (LDPE) films covered with active coatings containing mixtures of rosemary, raspberry, and pomegranate CO2 extracts were found to be active against selected bacterial strains that may extend the shelf life of food products. The coatings also offer antiviral activity, due to their influence on the activity of Φ6 bacteriophage, selected as a surrogate for SARS-CoV-2 particles. The mixture of these extracts could be incorporated into a polymer matrix to obtain a foil with antibacterial and antiviral properties. The initial goal of this work was to obtain active LDPE films containing a mixture of CO2 extracts of the aforementioned plants, incorporated into an LDPE matrix via an extrusion process. The second aim of this study was to demonstrate the antibacterial properties of the active films against Gram-positive and Gram-negative bacteria, and to determine the antiviral effect of the modified material on Φ6 bacteriophage. In addition, an analysis was made on the influence of the active mixture on the polymer physicochemical features, e.g., mechanical and thermal properties, as well as its color and transparency. The results of this research indicated that the LDPE film containing a mixture of raspberry, rosemary, and pomegranate CO2 extracts incorporated into an LDPE matrix inhibited the growth of Staphylococcus aureus. This film was also found to be active against Bacillus subtilis. This modified film did not inhibit the growth of Escherichia coli and Pseudomonas syringae cells; however, their number decreased significantly. The LDPE active film was also found to be active against Φ6 particles, meaning that the film had antiviral properties. The incorporation of the mixture of CO2 extracts into the polymer matrix affected its mechanical properties. It was observed that parameters describing mechanical properties decreased, although did not affect the transition of LDPE significantly. Additionally, the modified film exhibited barrier properties towards UV radiation. Modified PE/CO2 extracts films could be applied as a functional food packaging material with antibacterial and antiviral properties.


Subject(s)
Food Packaging/methods , Plant Extracts/pharmacology , Polyethylene/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Bacteriophage phi 6/drug effects , Biofilms , Chitosan/chemistry , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Plant Extracts/chemistry , Polyethylene/pharmacology , Polymers/chemistry , Pomegranate , Rosmarinus/chemistry , Rubus , SARS-CoV-2/drug effects
3.
Molecules ; 26(21)2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1512511

ABSTRACT

This work describes an untargeted analytical approach for the screening, identification, and characterization of the trans-epithelial transport of green tea (Camellia sinensis) catechin extracts with in vitro inhibitory effect against the SARS-CoV-2 papain-like protease (PLpro) activity. After specific catechin extraction, a chromatographic separation obtained six fractions were carried out. The fractions were assessed in vitro against the PLpro target. Fraction 5 showed the highest inhibitory activity against the SARS-CoV-2 PLpro (IC50 of 0.125 µg mL-1). The untargeted characterization revealed that (-)-epicatechin-3-gallate (ECG) was the most abundant compound in the fraction and the primary molecule absorbed by differentiated Caco-2 cells. Results indicated that fraction 5 was approximately 10 times more active than ECG (IC50 value equal to 11.62 ± 0.47 µg mL-1) to inhibit the PLpro target. Overall, our findings highlight the synergistic effects of the various components of the crude extract compared to isolated ECG.


Subject(s)
Catechin/pharmacology , Coronavirus Papain-Like Proteases/metabolism , Tea/metabolism , Antiviral Agents/chemistry , COVID-19/drug therapy , COVID-19/metabolism , Caco-2 Cells , Camellia sinensis/metabolism , Catechin/analogs & derivatives , Catechin/chemistry , Catechin/metabolism , Coronavirus Papain-Like Proteases/drug effects , Epithelium/drug effects , Epithelium/metabolism , Humans , Mass Spectrometry/methods , Plant Extracts/chemistry , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Tea/chemistry , Tea/physiology
4.
J Ethnopharmacol ; 284: 114797, 2022 Feb 10.
Article in English | MEDLINE | ID: covidwho-1487836

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: For millennia, Artemisia annua L. was used in Southeast Asia to treat "fever". This medicinal plant is effective against multiple pathogens and is used by many global communities as a source of artemisinin derivatives that are first-line drugs to treat malaria caused by Plasmodium parasites. AIM OF THE STUDY: The SARS-CoV-2 (Covid-19) global pandemic has killed millions and evolved numerous variants, with delta being the most transmissible to date and causing break-through infections of vaccinated individuals. We further queried the efficacy of A. annua cultivars against new variants. MATERIALS AND METHODS: Using Vero E6 cells, we measured anti-SARS-CoV-2 activity of dried-leaf hot-water A. annua L. extracts of four cultivars, A3, BUR, MED, and SAM, to determine their efficacy against five infectious variants of the virus: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and kappa (B.1.617.1). RESULTS: In addition to being effective against the original wild type (WT) WA1, A. annua cultivars A3, BUR, MED, and SAM were also potent against all five variants. IC50 and IC90 values based on measured artemisinin content ranged from 0.3 to 8.4 µM and 1.4-25.0 µM, respectively. The IC50 and IC90 values based on dried leaf weight (DW) used to make the tea infusions ranged from 11.0 to 67.7 µg DW and 59.5-160.6 µg DW, respectively. Cell toxicity was insignificant at a leaf dry weight of ≤50 µg in the extract of any cultivar. CONCLUSIONS: Results suggest that oral consumption of A. annua hot-water extracts (tea infusions) could potentially provide a cost-effective therapy to help stave off the rapid global spread of these variants, buying time for broader implementation of vaccines.


Subject(s)
Antiviral Agents/pharmacology , Artemisia annua/chemistry , COVID-19/virology , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Animals , Antiviral Agents/chemistry , Cell Survival/drug effects , Chlorocebus aethiops , Inhibitory Concentration 50 , Plant Extracts/chemistry , Vero Cells
5.
Molecules ; 26(20)2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1480885

ABSTRACT

In our in vitro and in vivo studies, we used Acalypha indica root methanolic extract (AIRME), and investigated their free radical scavenging/antioxidant and anti-inflammatory properties. Primarily, phytochemical analysis showed rich content of phenols (70.92 mg of gallic acid/g) and flavonoids (16.01 mg of rutin/g) in AIRME. We then performed HR-LC-MS and GC-MS analyses, and identified 101 and 14 phytochemical compounds, respectively. Among them, ramipril glucuronide (1.563%), antimycin A (1.324%), swietenine (1.134%), quinone (1.152%), oxprenolol (1.118%), choline (0.847%), bumetanide (0.847%) and fenofibrate (0.711%) are the predominant phytomolecules. Evidence from in vitro studies revealed that AIRME scavenges DPPH and hydroxyl radicals in a concentration dependent manner (10-50 µg/mL). Similarly, hydrogen peroxide and lipid peroxidation were also remarkably inhibited by AIRME as concentration increases (20-100 µg/mL). In vitro antioxidant activity of AIRME was comparable to ascorbic acid treatment. For in vivo studies, carrageenan (1%, sub-plantar) was injected to rats to induce localized inflammation. Acute inflammation was represented by paw-edema, and significantly elevated (p < 0.05) WBC, platelets and C-reactive protein (CRP). However, AIRME pretreatment (150/300 mg/kg bodyweight) significantly (p < 0.05) decreased edema volume. This was accompanied by a significant (p < 0.05) reduction of WBC, platelets and CRP with both doses of AIRME. The decreased activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in paw tissue were restored (p < 0.05 / p < 0.01) with AIRME in a dose-dependent manner. Furthermore, AIRME attenuated carrageenan-induced neutrophil infiltrations and vascular dilation in paw tissue. For the first time, our findings demonstrated the potent antioxidant and anti-inflammatory properties of AIRME, which could be considered to develop novel anti-inflammatory drugs.


Subject(s)
Acalypha/chemistry , Phytochemicals/chemistry , Phytochemicals/pharmacology , Plants, Medicinal/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Disease Models, Animal , Edema/drug therapy , Edema/enzymology , Edema/pathology , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , In Vitro Techniques , Male , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Rats , Rats, Wistar
6.
Molecules ; 26(20)2021 Oct 14.
Article in English | MEDLINE | ID: covidwho-1480883

ABSTRACT

Viral infections are among the most complex medical problems and have been a major threat to the economy and global health. Several epidemics and pandemics have occurred due to viruses, which has led to a significant increase in mortality and morbidity rates. Natural products have always been an inspiration and source for new drug development because of their various uses. Among all-natural sources, plant sources are the most dominant for the discovery of new therapeutic agents due to their chemical and structural diversity. Despite the traditional use and potential source for drug development, natural products have gained little attention from large pharmaceutical industries. Several plant extracts and isolated compounds have been extensively studied and explored for antiviral properties against different strains of viruses. In this review, we have compiled antiviral plant extracts and natural products isolated from plants reported since 2015.


Subject(s)
Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Biological Products/pharmacology , Drug Development , Plant Extracts/pharmacology , Animals , Anti-HIV Agents/chemistry , Anti-HIV Agents/isolation & purification , Anti-HIV Agents/pharmacology , Antiviral Agents/chemistry , Biological Products/chemistry , Biological Products/isolation & purification , Drug Discovery , Flavivirus/drug effects , Hepatitis Viruses/drug effects , Humans , Molecular Structure , Orthomyxoviridae/drug effects , Plant Extracts/chemistry , Simplexvirus/drug effects
7.
Int J Biol Macromol ; 187: 976-987, 2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1474606

ABSTRACT

Coronavirus 3C-like protease (3CLpro) is a crucial target for treating coronavirus diseases including COVID-19. Our preliminary screening showed that Ampelopsis grossedentata extract (AGE) displayed potent SARS-CoV-2-3CLpro inhibitory activity, but the key constituents with SARS-CoV-2-3CLpro inhibitory effect and their mechanisms were unrevealed. Herein, a practical strategy via integrating bioactivity-guided fractionation and purification, mass spectrometry-based peptide profiling and time-dependent biochemical assay, was applied to identify the crucial constituents in AGE and to uncover their inhibitory mechanisms. The results demonstrated that the flavonoid-rich fractions (10-17.5 min) displayed strong SARS-CoV-2-3CLpro inhibitory activities, while the constituents in these fractions were isolated and their SARS-CoV-2-3CLpro inhibitory activities were investigated. Among all isolated flavonoids, dihydromyricetin, isodihydromyricetin and myricetin strongly inhibited SARS-CoV-2 3CLpro in a time-dependent manner. Further investigations demonstrated that myricetin could covalently bind on SARS-CoV-2 3CLpro at Cys300 and Cys44, while dihydromyricetin and isodihydromyricetin covalently bound at Cys300. Covalent docking coupling with molecular dynamics simulations showed the detailed interactions between the orthoquinone form of myricetin and two covalent binding sites (surrounding Cys300 and Cys44) of SARS-CoV-2 3CLpro. Collectively, the flavonoids in AGE strongly and time-dependently inhibit SARS-CoV-2 3CLpro, while the newly identified SARS-CoV-2 3CLpro inhibitors in AGE offer promising lead compounds for developing novel antiviral agents.


Subject(s)
3C Viral Proteases/chemistry , 3C Viral Proteases/metabolism , Ampelopsis/chemistry , Antiviral Agents/pharmacology , Flavonoids/pharmacology , SARS-CoV-2/enzymology , Antiviral Agents/chemistry , Binding Sites/drug effects , Cysteine/metabolism , Flavonoids/chemistry , Flavonols/chemistry , Flavonols/pharmacology , Mass Spectrometry , Models, Molecular , Molecular Docking Simulation , Molecular Dynamics Simulation , Plant Extracts/chemistry , Plant Extracts/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Protein Binding/drug effects , Protein Conformation/drug effects , SARS-CoV-2/drug effects
8.
Molecules ; 26(20)2021 Oct 14.
Article in English | MEDLINE | ID: covidwho-1470935

ABSTRACT

Excessive host inflammation following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with severity and mortality in coronavirus disease 2019 (COVID-19). We recently reported that the SARS-CoV-2 spike protein S1 subunit (S1) induces pro-inflammatory responses by activating toll-like receptor 4 (TLR4) signaling in macrophages. A standardized extract of Asparagus officinalis stem (EAS) is a unique functional food that elicits anti-photoaging effects by suppressing pro-inflammatory signaling in hydrogen peroxide and ultraviolet B-exposed skin fibroblasts. To elucidate its potential in preventing excessive inflammation in COVID-19, we examined the effects of EAS on pro-inflammatory responses in S1-stimulated macrophages. Murine peritoneal exudate macrophages were co-treated with EAS and S1. Concentrations and mRNA levels of pro-inflammatory cytokines were assessed using enzyme-linked immunosorbent assay and reverse transcription and real-time polymerase chain reaction, respectively. Expression and phosphorylation levels of signaling proteins were analyzed using western blotting and fluorescence immunomicroscopy. EAS significantly attenuated S1-induced secretion of interleukin (IL)-6 in a concentration-dependent manner without reducing cell viability. EAS also markedly suppressed the S1-induced transcription of IL-6 and IL-1ß. However, among the TLR4 signaling proteins, EAS did not affect the degradation of inhibitor κBα, nuclear translocation of nuclear factor-κB p65 subunit, and phosphorylation of c-Jun N-terminal kinase p54 subunit after S1 exposure. In contrast, EAS significantly suppressed S1-induced phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and Akt. Attenuation of S1-induced transcription of IL-6 and IL-1ß by the MAPK kinase inhibitor U0126 was greater than that by the Akt inhibitor perifosine, and the effects were potentiated by simultaneous treatment with both inhibitors. These results suggest that EAS attenuates S1-induced IL-6 and IL-1ß production by suppressing p44/42 MAPK and Akt signaling in macrophages. Therefore, EAS may be beneficial in regulating excessive inflammation in patients with COVID-19.


Subject(s)
Asparagus Plant/chemistry , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Macrophages/drug effects , Plant Extracts/pharmacology , Signal Transduction/drug effects , Animals , Asparagus Plant/metabolism , Butadienes/pharmacology , Cell Survival/drug effects , Interleukin-1beta/genetics , Interleukin-6/genetics , Macrophages/cytology , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/metabolism , Nitriles/pharmacology , Phosphorylation/drug effects , Plant Extracts/chemistry , Plant Stems/chemistry , Plant Stems/metabolism , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Spike Glycoprotein, Coronavirus/pharmacology , Toll-Like Receptor 4/metabolism , Transcription, Genetic/drug effects
9.
Chem Res Toxicol ; 34(10): 2169-2179, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1461948

ABSTRACT

The outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) has been cause for concern to the medical community, particularly given that this novel illness has coincided with the COVID-19 pandemic, another cause of severe pulmonary illness. Though cannabis e-cigarettes tainted with vitamin E acetate were primarily associated with EVALI, acute lung injuries stemming from cannabis inhalation were reported in the literature prior to 2019, and it has been suggested that cannabis components or additives other than vitamin E acetate may be responsible. Despite these concerning issues, novel cannabis vaporizer ingredients continue to arise, such as Δ8-tetrahydrocannabinol, Δ10-tetrahydrocannabinol, hexahydrocannabinol, and cannabichromene. In order to address cannabis e-cigarette safety and vaping in an effective manner, we provide a comprehensive knowledge of the latest products, delivery modes, and ingredients. This perspective highlights the types of cannabis vaping modalities common to the United States cannabis market, with special attention to cartridge-type cannabis e-cigarette toxicology and their involvement in the EVALI outbreak, in particular, acute lung injurious responses. Novel ingredient chemistry, origins, and legal statuses are reviewed, as well as the toxicology of known cannabis e-cigarette aerosol components.


Subject(s)
Cannabis/chemistry , Lung Injury/etiology , Marijuana Smoking/adverse effects , Plant Extracts/chemistry , Aerosols/chemistry , Aerosols/toxicity , Cannabis/metabolism , Dronabinol/chemistry , Dronabinol/toxicity , Electronic Nicotine Delivery Systems , Humans , Plant Extracts/toxicity , Vitamin E/chemistry
10.
Biomed Res Int ; 2021: 1636816, 2021.
Article in English | MEDLINE | ID: covidwho-1455769

ABSTRACT

Respiratory inflammation is caused by an air-mediated disease induced by polluted air, smoke, bacteria, and viruses. The COVID-19 pandemic is also a kind of respiratory disease, induced by a virus causing a serious effect on the lungs, bronchioles, and pharynges that results in oxygen deficiency. Extensive research has been conducted to find out the potent natural products that help to prevent, treat, and manage respiratory diseases. Traditionally, wider floras were reported to be used, such as Morus alba, Artemisia indica, Azadirachta indica, Calotropis gigantea, but only some of the potent compounds from some of the plants have been scientifically validated. Plant-derived natural products such as colchicine, zingerone, forsythiaside A, mangiferin, glycyrrhizin, curcumin, and many other compounds are found to have a promising effect on treating and managing respiratory inflammation. In this review, current clinically approved drugs along with the efficacy and side effects have been studied. The study also focuses on the traditional uses of medicinal plants on reducing respiratory complications and their bioactive phytoconstituents. The pharmacological evidence of lowering respiratory complications by plant-derived natural products has been critically studied with detailed mechanism and action. However, the scientific validation of such compounds requires clinical study and evidence on animal and human models to replace modern commercial medicine.


Subject(s)
COVID-19 , Pandemics , Phytochemicals/therapeutic use , Plant Extracts/therapeutic use , Plants, Medicinal/chemistry , SARS-CoV-2 , Animals , COVID-19/drug therapy , COVID-19/epidemiology , Humans , Inflammation/drug therapy , Inflammation/epidemiology , Phytochemicals/chemistry , Plant Extracts/chemistry
11.
J Ovarian Res ; 14(1): 126, 2021 Sep 27.
Article in English | MEDLINE | ID: covidwho-1440942

ABSTRACT

BACKGROUND: Infections by the SARS-CoV-2 virus causing COVID-19 are presently a global emergency. The current vaccination effort may reduce the infection rate, but strain variants are emerging under selection pressure. Thus, there is an urgent need to find drugs that treat COVID-19 and save human lives. Hence, in this study, we identified phytoconstituents of an edible vegetable, Bitter melon (Momordica charantia), that affect the SARS-CoV-2 spike protein. METHODS: Components of Momordica charantia were tested to identify the compounds that bind to the SARS-CoV-2 spike protein. An MTiOpenScreen web-server was used to perform docking studies. The Lipinski rule was utilized to evaluate potential interactions between the drug and other target molecules. PyMol and Schrodinger software were used to identify the hydrophilic and hydrophobic interactions. Surface plasmon resonance (SPR) was employed to assess the interaction between an extract component (erythrodiol) and the spike protein. RESULTS: Our in-silico evaluations showed that phytoconstituents of Momordica charantia have a low binding energy range, -5.82 to -5.97 kcal/mol. A docking study revealed two sets of phytoconstituents that bind at the S1 and S2 domains of SARS-CoV-2. SPR showed that erythrodiol has a strong binding affinity (KD = 1.15 µM) with the S2 spike protein of SARS-CoV-2. Overall, docking, ADME properties, and SPR displayed strong interactions between phytoconstituents and the active site of the SARS-CoV-2 spike protein. CONCLUSION: This study reveals that phytoconstituents from bitter melon are potential agents to treat SARS-CoV-2 viral infections due to their binding to spike proteins S1 and S2.


Subject(s)
COVID-19/drug therapy , Momordica charantia/chemistry , Plant Extracts/pharmacology , Spike Glycoprotein, Coronavirus/genetics , Binding Sites/drug effects , COVID-19/genetics , COVID-19/virology , Humans , Hydrophobic and Hydrophilic Interactions/drug effects , Molecular Docking Simulation , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/chemistry , Oleanolic Acid/pharmacology , Plant Extracts/chemistry , Protein Binding/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Surface Plasmon Resonance
12.
Molecules ; 26(19)2021 Sep 27.
Article in English | MEDLINE | ID: covidwho-1438676

ABSTRACT

In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were isolated from the leaves of Pimenta dioica (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds (1-4) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC50) and SARS-CoV-2 inhibitory concentrations (IC50). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with P. dioca aqueous extract, ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were recorded through measuring TNF-α, IL-1ß, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin 2, gallic acid 3, and chlorogenic acid 4 showed remarkable anti-SARS-CoV-2 activities with IC50 values of 31 µg/mL, 108 µg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid 1 and rutin 2 treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin 2 either alone or in combination with other isolates for COVID-19 management.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Animals , Anti-Inflammatory Agents/chemistry , Antiviral Agents/chemistry , Chlorocebus aethiops , Chlorogenic Acid/isolation & purification , Chlorogenic Acid/pharmacology , Coumaric Acids/isolation & purification , Coumaric Acids/pharmacology , Gallic Acid/isolation & purification , Gallic Acid/pharmacology , Humans , Male , Molecular Docking Simulation , Molecular Dynamics Simulation , Plant Extracts/chemistry , Rats , Rutin/isolation & purification , Rutin/pharmacology , Vero Cells
13.
Molecules ; 26(18)2021 Sep 12.
Article in English | MEDLINE | ID: covidwho-1410349

ABSTRACT

Chemical and biological investigation of the Madagascar endemic plant Saldinia proboscidea led to the isolation of an isomer of artemisinin, (-)-6-epi-artemisinin (2). Its structure was elucidated using a combination of NMR and mass spectrometry. The absolute configuration was established by chemical syntheses of compound 2 as well as a new stereoisomer (3). The comparable bioactivities of artemisinin (1) and its isomer (-)-6-epi-artemisinin (2) revealed that this change in configuration was not critical to their biological properties. Bioactivity was assessed using an apoptosis induction assay, a SARS-CoV-2 inhibitor assay, and a haematin polymerization inhibitory activity (HPIA) assay. This is the first report of an artemisinin-related compound from a genus not belonging to Artemisia and it is the first isolation of an artemisinin-related natural product that is the opposite enantiomeric series relative to artemisinin from Artemisia annua.


Subject(s)
Antimalarials/chemistry , Artemisinins/chemistry , Plant Extracts/chemistry , Rubiaceae/chemistry , Madagascar , Stereoisomerism
14.
Virol J ; 18(1): 182, 2021 09 08.
Article in English | MEDLINE | ID: covidwho-1403244

ABSTRACT

BACKGROUND: Traditional medicines based on herbal extracts have been proposed as affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Teas and drinks containing extracts of Artemisia annua and Artemisia afra have been widely used in Africa in efforts to prevent SARS-CoV-2 infection and fight COVID-19. METHODS: The plant extracts and Covid-Organics drink produced in Madagascar were tested for plaque reduction using both feline coronavirus and SARS-CoV-2 in vitro. Their cytotoxicities were also investigated. RESULTS: Several extracts as well as Covid-Organics inhibited SARS-CoV-2 and FCoV infection at concentrations that did not affect cell viability. CONCLUSIONS: Some plant extracts show inhibitory activity against FCoV and SARS-CoV-2. However, it remains unclear whether peak plasma concentrations in humans can reach levels needed to inhibit viral infection following consumption of teas or Covid-Organics. Clinical studies are required to evaluate the utility of these drinks for COVID-19 prevention or treatment of patients.


Subject(s)
Antiviral Agents/pharmacology , Artemisia/chemistry , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Animals , Antiviral Agents/chemistry , Cell Line , Cell Survival/drug effects , Coronavirus, Feline/drug effects , Coronavirus, Feline/growth & development , Plant Extracts/chemistry , SARS-CoV-2/growth & development , Viral Plaque Assay
15.
Molecules ; 26(17)2021 Aug 25.
Article in English | MEDLINE | ID: covidwho-1399347

ABSTRACT

Lippia graveolens is a traditional crop and a rich source of bioactive compounds with various properties (e.g., antioxidant, anti-inflammatory, antifungal, UV defense, anti-glycemic, and cytotoxicity) that is primarily cultivated for essential oil recovery. The isolated bioactive compounds could be useful as additives in the functional food, nutraceuticals, cosmetics, and pharmaceutical industries. Carvacrol, thymol, ß-caryophyllene, and p-cymene are terpene compounds contained in oregano essential oil (OEO); flavonoids such as quercetin O-hexoside, pinocembrin, and galangin are flavonoids found in oregano extracts. Furthermore, thermoresistant compounds that remain in the plant matrix following a thermal process can be priced in terms of the circular economy. By using better and more selective extraction conditions, the bioactive compounds present in Mexican oregano can be studied as potential inhibitors of COVID-19. Also, research on extraction technologies should continue to ensure a higher quality of bioactive compounds while preventing an undesired chemical shift (e.g., hydrolysis). The oregano fractions can be used in the food, health, and agricultural industries.


Subject(s)
Lippia/chemistry , Phytochemicals/therapeutic use , Plant Extracts/therapeutic use , COVID-19/drug therapy , Cosmetics , Dietary Supplements , Functional Food , Humans , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , SARS-CoV-2/drug effects
16.
Molecules ; 26(6)2021 Mar 23.
Article in English | MEDLINE | ID: covidwho-1389468

ABSTRACT

Natural products are gaining more interest recently, much of which focuses on those derived from medicinal plants. The common chicory (Cichorium intybus L.), of the Astraceae family, is a prime example of this trend. It has been proven to be a feasible source of biologically relevant elements (K, Fe, Ca), vitamins (A, B1, B2, C) as well as bioactive compounds (inulin, sesquiterpene lactones, coumarin derivatives, cichoric acid, phenolic acids), which exert potent pro-health effects on the human organism. It displays choleretic and digestion-promoting, as well as appetite-increasing, anti-inflammatory and antibacterial action, all owing to its varied phytochemical composition. Hence, chicory is used most often to treat gastrointestinal disorders. Chicory was among the plants with potential against SARS-CoV-2, too. To this and other ends, roots, herb, flowers and leaves are used. Apart from its phytochemical applications, chicory is also used in gastronomy as a coffee substitute, food or drink additive. The aim of this paper is to present, in the light of the recent literature, the chemical composition and properties of chicory.


Subject(s)
Chicory/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antiparasitic Agents/chemistry , Antiparasitic Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Chicory/physiology , Cooking , Food Hypersensitivity/etiology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Plants, Medicinal/chemistry
17.
Molecules ; 26(16)2021 Aug 06.
Article in English | MEDLINE | ID: covidwho-1376914

ABSTRACT

Sea buckthorn (Hippophae rhamnoides L. (HR)) leaf powders are the underutilized, promising resource of valuable compounds. Genotype and processing methods are key factors in the preparation of homogenous, stable, and quantified ingredients. The aim of this study was to evaluate the phenolic, triterpenic, antioxidant profiles, carotenoid and chlorophyll content, and chromatic characteristics of convection-dried and freeze-dried HR leaf powders obtained from ten different female cultivars, namely 'Avgustinka', 'Botaniceskaja Liubitelskaja', 'Botaniceskaja', 'Hibrid Percika', 'Julia', 'Nivelena', 'Otradnaja', 'Podarok Sadu', 'Trofimovskaja', and 'Vorobjovskaja'. The chromatic characteristics were determined using the CIELAB scale. The phytochemical profiles were determined using HPLC-PDA (high performance liquid chromatography with photodiode array detector) analysis; spectrophotometric assays and antioxidant activities were investigated using ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (ferric ion reducing antioxidant power) assays. The sea buckthorn leaf powders had a yellowish-green appearance. The drying mode had a significant impact on the total antioxidant activity, chlorophyll content, and chromatic characteristics of the samples; the freeze-dried samples were superior in antioxidant activity, chlorophyll, carotenoid content, and chromatic profile, compared to convection-dried leaf powder samples. The determined triterpenic and phenolic profiles strongly depend on the cultivar, and the drying technique had no impact on qualitative and quantitative composition. Catechin, epigallocatechin, procyanidin B3, ursolic acid, α-amyrin, and ß-sitosterol could be used as quantitative markers in the phenolic and triterpenic profiles. The cultivars 'Avgustinka', 'Nivelena', and 'Botaniceskaja' were superior to other tested cultivars, with the phytochemical composition and antioxidant activity.


Subject(s)
Antioxidants/chemistry , Antioxidants/pharmacology , Desiccation , Hippophae/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Powders
18.
Int J Mol Sci ; 22(16)2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1376839

ABSTRACT

Wogonin is one of the most active flavonoids from Scutellaria baicalensis Georgi (baikal skullcap), widely used in traditional Chinese medicine. It exhibits a broad spectrum of health-promoting and therapeutic activities. Together with baicalein, it is considered to be the one of main active ingredients of Chinese medicines for the management of COVID-19. However, therapeutic use of wogonin may be limited due to low market availability connected with its low content in baikal skullcap and lack of efficient preparative methods for obtaining this compound. Although the amount of wogonin in skullcap root often does not exceed 0.5%, this material is rich in wogonin glucuronide, which may be used as a substrate for wogonin production. In the present study, a rapid, simple, cheap and effective method of wogonin and baicalein preparation, which provides gram quantities of both flavonoids, is proposed. The obtained wogonin was used as a substrate for biotransformation. Thirty-six microorganisms were tested in screening studies. The most efficient were used in enlarged scale transformations to determine metabolism of this xenobiotic. The major phase I metabolism product was 4'-hydroxywogonin-a rare flavonoid which exhibits anticancer activity-whereas phase II metabolism products were glucosides of wogonin. The present studies complement and extend the knowledge on the effect of substitution of A- and B-ring on the regioselective glycosylation of flavonoids catalyzed by microorganisms.


Subject(s)
Flavanones/chemistry , Flavanones/pharmacology , Scutellaria baicalensis/chemistry , Animals , Biotransformation , COVID-19/drug therapy , Flavanones/isolation & purification , Flavanones/pharmacokinetics , Fungi/drug effects , Humans , Microbial Sensitivity Tests , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , SARS-CoV-2/drug effects
19.
Bioorg Med Chem ; 45: 116329, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1372898

ABSTRACT

Agrimonia pilosa (AP), Galla rhois (RG), and their mixture (APRG64) strongly inhibited SARS-CoV-2 by interfering with multiple steps of the viral life cycle including viral entry and replication. Furthermore, among 12 components identified in APRG64, three displayed strong antiviral activity, ursolic acid (1), quercetin (7), and 1,2,3,4,6-penta-O-galloyl-ß-d-glucose (12). Molecular docking analysis showed these components to bind potently to the spike receptor-binding-domain (RBD) of the SARS-CoV-2 and its variant B.1.1.7. Taken together, these findings indicate APRG64 as a potent drug candidate to treat SARS-CoV-2 and its variants.


Subject(s)
Agrimonia/chemistry , Antiviral Agents/chemistry , Biological Products/chemistry , COVID-19/drug therapy , Plant Extracts/chemistry , SARS-CoV-2/drug effects , Amino Acid Sequence , Antiviral Agents/pharmacology , Biological Products/pharmacology , Drug Discovery , Humans , Hydrolyzable Tannins/chemistry , Molecular Docking Simulation , Plant Extracts/pharmacology , Protein Binding , Quercetin/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Triterpenes/chemistry , Virus Internalization/drug effects
20.
Molecules ; 26(17)2021 Aug 28.
Article in English | MEDLINE | ID: covidwho-1374472

ABSTRACT

This study aims to identify and isolate the secondary metabolites of Zingiber officinale using GC-MS, preparative TLC, and LC-MS/MS methods, to evaluate the inhibitory potency on SARS-CoV-2 3 chymotrypsin-like protease enzyme, as well as to study the molecular interaction and stability by using docking and molecular dynamics simulations. GC-MS analysis suggested for the isolation of terpenoids compounds as major compounds on methanol extract of pseudostems and rhizomes. Isolation and LC-MS/MS analysis identified 5-hydro-7, 8, 2'-trimethoxyflavanone (9), (E)-hexadecyl-ferulate (1), isocyperol (2), N-isobutyl-(2E,4E)-octadecadienamide (3), and nootkatone (4) from the rhizome extract, as well as from the leaves extract with the absence of 9. Three known steroid compounds, i.e., spinasterone (7), spinasterol (8), and 24-methylcholesta-7-en-3ß-on (6), were further identified from the pseudostem extract. Molecular docking showed that steroids compounds 7, 8, and 6 have lower predictive binding energies (MMGBSA) than other metabolites with binding energy of -87.91, -78.11, and -68.80 kcal/mole, respectively. Further characterization on the single isolated compound by NMR showed that 6 was identified and possessed 75% inhibitory activity on SARS-CoV-2 3CL protease enzyme that was slightly different with the positive control GC376 (77%). MD simulations showed the complex stability with compound 6 during 100 ns simulation time.


Subject(s)
COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus Protease Inhibitors/pharmacology , Ginger/chemistry , Plant Extracts/pharmacology , Coronavirus 3C Proteases/metabolism , Coronavirus 3C Proteases/ultrastructure , Coronavirus Protease Inhibitors/chemistry , Coronavirus Protease Inhibitors/isolation & purification , Coronavirus Protease Inhibitors/therapeutic use , Crystallography, X-Ray , Enzyme Assays , Gas Chromatography-Mass Spectrometry , Humans , Magnetic Resonance Spectroscopy , Molecular Docking Simulation , Molecular Dynamics Simulation , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Pyrrolidines/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Structure-Activity Relationship , Sulfonic Acids/pharmacology
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