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1.
Molecules ; 27(4)2022 Feb 21.
Article in English | MEDLINE | ID: covidwho-1715568

ABSTRACT

Baicalin is a major active ingredient of traditional Chinese medicine Scutellaria baicalensis, and has been shown to have antiviral, anti-inflammatory, and antitumor activities. However, the protein targets of baicalin have remained unclear. Herein, a chemical proteomics strategy was developed by combining baicalin-functionalized magnetic nanoparticles (BCL-N3@MNPs) and quantitative mass spectrometry to identify the target proteins of baicalin. Bioinformatics analysis with the use of Gene Ontology, STRING and Ingenuity Pathway Analysis, was performed to annotate the biological functions and the associated signaling pathways of the baicalin targeting proteins. Fourteen proteins in human embryonic kidney cells were identified to interact with baicalin with various binding affinities. Bioinformatics analysis revealed these proteins are mainly ATP-binding and/or ATPase activity proteins, such as CKB, HSP86, HSP70-1, HSP90, ATPSF1ß and ACTG1, and highly associated with the regulation of the role of PKR in interferon induction and the antiviral response signaling pathway (P = 10-6), PI3K/AKT signaling pathway (P = 10-5) and eNOS signaling pathway (P = 10-4). The results show that baicalin exerts multiply pharmacological functions, such as antiviral, anti-inflammatory, antitumor, and antioxidant functions, through regulating the PKR and PI3K/AKT/eNOS signaling pathways by targeting ATP-binding and ATPase activity proteins. These findings provide a fundamental insight into further studies on the mechanism of action of baicalin.


Subject(s)
Flavonoids/pharmacology , HSP70 Heat-Shock Proteins/antagonists & inhibitors , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Nitric Oxide Synthase Type III/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Animals , Dose-Response Relationship, Drug , Flavonoids/administration & dosage , Flavonoids/chemistry , Humans , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/ultrastructure , Protein Interaction Mapping
2.
Food Funct ; 11(4): 3516-3526, 2020 Apr 30.
Article in English | MEDLINE | ID: covidwho-726012

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease with few successful treatments, and is strongly associated with cigarette smoking (CS). Since the novel coronavirus has spread worldwide seriously, there is growing concern that patients who have chronic respiratory conditions like COPD can easily be infected and are more prone to having severe illness and even mortality because of lung dysfunction. Loquat leaves have long been used as an important material for both pharmaceutical and functional applications in the treatment of lung disease in Asia, especially in China and Japan. Total flavonoids (TF), the main active components derived from loquat leaves, showed remarkable anti-inflammatory and antioxidant activities. However, their protective activity against CS-induced COPD airway inflammation and oxidative stress and its underlying mechanism still remain not well-understood. The present study uses a CS-induced mouse model to estimate the morphological changes in lung tissue. The results demonstrated that TF suppressed the histological changes in the lungs of CS-challenged mice, as evidenced by reduced generation of pro-inflammatory cytokines including interleukin 6 (IL-6), IL-1ß, tumor necrosis factor α (TNF-α), nitric oxide (NO), and inducible nitric oxide synthase (iNOS) and diminished the protein expression of transient receptor potential vanilloid 1 (TRPV1). Moreover, TF also inhibited phosphorylation of IKK, IκB and NFκB and increased p-Akt. Interestingly, TF could inhibit CS-induced oxidative stress in the lungs of COPD mice. TF treatment significantly inhibited the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD). In addition, TF markedly downregulated TRPV1 and cytochrome P450 2E1 (CYP2E1) and upregulated the expression of SOD-2, while the p-JNK level was observed to be inhibited in COPD mice. Taken together, our findings showed that the protective effect and putative mechanism of the action of TF resulted in the inhibition of inflammation and oxidative stress through the regulation of TRPV1 and the related signal pathway in lung tissues. It suggested that TF derived from loquat leaves could be considered to be an alternative or a new functional material and used for the treatment of CS-induced COPD.


Subject(s)
Cigarette Smoking/adverse effects , Drugs, Chinese Herbal/administration & dosage , Eriobotrya/chemistry , Flavonoids/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , TRPV Cation Channels/immunology , Animals , Cytochrome P-450 CYP2E1/genetics , Cytochrome P-450 CYP2E1/immunology , Humans , Interleukin-6/genetics , Interleukin-6/immunology , Male , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effects , Plant Leaves/chemistry , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/immunology , Signal Transduction/drug effects , Smoke/adverse effects , Superoxide Dismutase/genetics , Superoxide Dismutase/immunology , TRPV Cation Channels/genetics
3.
Int J Mol Sci ; 21(9)2020 Apr 28.
Article in English | MEDLINE | ID: covidwho-133432

ABSTRACT

BACKGROUND: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.


Subject(s)
Antioxidants/administration & dosage , Betacoronavirus , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Diet , Dietary Supplements , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Adiponectin/metabolism , Ascorbic Acid/administration & dosage , COVID-19 , Coronavirus Infections/metabolism , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/metabolism , Flavonoids/administration & dosage , Humans , Interleukin-6/immunology , Interleukin-6/metabolism , Lung Diseases/immunology , Lung Diseases/metabolism , Lung Diseases/therapy , Pandemics , Pneumonia, Viral/metabolism , SARS-CoV-2 , Tumor Necrosis Factor-alpha/metabolism
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