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1.
Oxid Med Cell Longev ; 2022: 4748447, 2022.
Article in English | MEDLINE | ID: covidwho-2214085

ABSTRACT

The world's population is ageing at an accelerated pace. Ageing is a natural, physiological but highly complex and multifactorial process that all species in the Tree of Life experience over time. Physical and mental disabilities, and age-related diseases, would increase along with the increasing life expectancy. Ginger (Zingiber officinale) is a plant that belongs to the Zingiberaceae family, native to Southeast Asia. For hundreds of years, ginger has been consumed in various ways by the natives of Asian countries, both as culinary and medicinal herb for the treatment of many diseases. Mounting evidence suggests that ginger can promote healthy ageing, reduce morbidity, and prolong healthy lifespan. Ginger, a well-known natural product, has been demonstrated to possess antioxidant, anti-inflammatory, anticancer, and antimicrobial properties, as well as an outstanding antiviral activity due to a high concentration of antiviral compounds. In this review, the current evidence on the potential role of ginger and its active compounds in the prevention of ageing is discussed.


Subject(s)
Ginger , Healthy Aging , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antiviral Agents , Plant Extracts/pharmacology , Plant Extracts/therapeutic use
2.
Comb Chem High Throughput Screen ; 25(14): 2315-2316, 2022.
Article in English | MEDLINE | ID: covidwho-2141208
3.
Int J Mol Sci ; 23(21)2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2099581

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world's population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19. In this report, we evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5. Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects. Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Ceramides , COVID-19/drug therapy , Disease Models, Animal , Fluoxetine/pharmacology , Fluoxetine/therapeutic use
4.
J Ethnopharmacol ; 299: 115674, 2022 Dec 05.
Article in English | MEDLINE | ID: covidwho-2069311

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. AIM OF THE STUDY: Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. MATERIALS AND METHODS: The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. RESULTS: The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. CONCLUSIONS: The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research.


Subject(s)
Acute Lung Injury , Antitussive Agents , Drugs, Chinese Herbal , Immunomodulating Agents , Acute Lung Injury/drug therapy , Analgesics/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antitussive Agents/therapeutic use , Cytokines/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Essential/therapeutic use , Immunomodulating Agents/pharmacology , Immunomodulating Agents/therapeutic use , Mice , Network Pharmacology/methods , Rats , Receptors, Antigen, T-Cell/therapeutic use
5.
Viruses ; 14(10)2022 09 27.
Article in English | MEDLINE | ID: covidwho-2066543

ABSTRACT

Curcumin, the bioactive compound of the spice Curcuma longa, has already been reported as a potential COVID-19 adjuvant treatment due to its immunomodulatory and anti-inflammatory properties. In this study, SARS-CoV-2 was challenged with curcumin; moreover, curcumin was also coupled with laser light at 445 nm in a photodynamic therapy approach. Curcumin at a concentration of 10 µM, delivered to the virus prior to inoculation on cell culture, inhibited SARS-CoV-2 replication (reduction >99%) in Vero E6 cells, possibly due to disruption of the virion structure, as observed using the RNase protection assay. However, curcumin was not effective as a prophylactic treatment on already-infected Vero E6 cells. Notably, when curcumin was employed as a photosensitizer and blue laser light at 445 nm was delivered to a mix of curcumin/virus prior to the inoculation on the cells, virus inactivation was observed (>99%) using doses of curcumin that were not antiviral by themselves. Photodynamic therapy employing crude curcumin can be suggested as an antiviral option against SARS-CoV-2 infection.


Subject(s)
COVID-19 , Curcumin , Chlorocebus aethiops , Animals , Humans , SARS-CoV-2 , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Curcumin/pharmacology , COVID-19/drug therapy , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Vero Cells , Anti-Inflammatory Agents/pharmacology , Ribonucleases/pharmacology , Virus Replication
6.
Molecules ; 27(19)2022 Sep 20.
Article in English | MEDLINE | ID: covidwho-2066270

ABSTRACT

Andrographis paniculata is a well-known Asian medicinal plant with a major phytoconstituent of diterpene lactones, such as andrographolide, 14-deoxyandrographolide, and neoandrographolide. A World Health Organization (WHO) monograph on selected medicinal plants showed that A. paniculata extracts and its major diterpene lactones have promising anti-inflammatory, antidiabetic, antimalarial, anticancer, antifungal, antibacterial, antioxidant, and hypoglycemic activities. However, these active phytochemicals have poor water solubility and bioavailability when delivered in a conventional dosage form. These biological barriers can be mitigated if the extract or isolated compound are delivered as nanoparticles. This review discusses existing studies and marketed products of A. paniculata in solid, liquid, semi-solid, and gaseous dosage forms, either as an extract or isolated pure compounds, as well as their deficits in reaching maximum bioavailability. The pharmaceutics and pharmacological activity of A. paniculata as a nano-delivery system are also discussed.


Subject(s)
Andrographis , Antimalarials , Diterpenes , Plants, Medicinal , Andrographis/chemistry , Andrographis paniculata , Anti-Bacterial Agents , Anti-Inflammatory Agents/pharmacology , Antifungal Agents , Antioxidants , Diterpenes/chemistry , Hypoglycemic Agents , Lactones , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Water
7.
Int J Mol Sci ; 23(19)2022 Sep 20.
Article in English | MEDLINE | ID: covidwho-2066116

ABSTRACT

Naturally occurring bioactives, also known as phytochemicals, have been widely recognized and researched owing to their multiple potentialities [...].


Subject(s)
Anti-Inflammatory Agents , Phytochemicals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Phytochemicals/pharmacology , Phytochemicals/therapeutic use
8.
Life Sci ; 309: 121048, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2061633

ABSTRACT

Pirfenidone (PFD) is a non-peptide synthetic chemical that inhibits the production of transforming growth factor-beta 1 (TGF-ß1), tumor necrosis factor-alpha (TNF-α), platelet-derived growth factor (PDGF), Interleukin 1 beta (IL-1ß), and collagen 1 (COL1A1), all of which have been linked to the prevention or removal of excessive scar tissue deposition in many organs. PFD has been demonstrated to decrease apoptosis, downregulate angiotensin-converting enzyme (ACE) receptor expression, reduce inflammation through many routes, and alleviate oxidative stress in pneumocytes and other cells while protecting them from COVID-19 invasion and cytokine storm. Based on the mechanism of action of PFD and the known pathophysiology of COVID-19, it was recommended to treat COVID-19 patients. The use of PFD as a treatment for a range of disorders is currently being studied, with an emphasis on outcomes related to reduced inflammation and fibrogenesis. As a result, rather than exploring the molecule's chemical characteristics, this review focuses on innovative PFD efficacy data. Briefly, herein we tried to investigate, discuss, and illustrate the possible mechanisms of actions for PFD to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2 candidate.


Subject(s)
COVID-19 , Transforming Growth Factor beta1 , Humans , Transforming Growth Factor beta1/metabolism , Antioxidants/pharmacology , Antioxidants/therapeutic use , Tumor Necrosis Factor-alpha , Interleukin-1beta , SARS-CoV-2 , COVID-19/drug therapy , Fibrosis , Pyridones/pharmacology , Pyridones/therapeutic use , Collagen Type I/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Platelet-Derived Growth Factor , Inflammation/drug therapy , Transforming Growth Factors , Angiotensins
9.
Clin Immunol ; 244: 109093, 2022 11.
Article in English | MEDLINE | ID: covidwho-2049018

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated, which results in a cytokine storm at the late stage of COVID-19. Autophagy regulation is involved in the infection and replication of SARS-CoV-2 at the early stage and the inhibition of NLRP3 inflammasome-mediated lung inflammation at the late stage of COVID-19. Here, we discuss the autophagy regulation at different stages of COVID-19. Specifically, we highlight the therapeutic potential of autophagy activators in COVID-19 by inhibiting the NLRP3 inflammasome, thereby avoiding the cytokine storm. We hope this review provides enlightenment for the use of autophagy activators targeting the inhibition of the NLRP3 inflammasome, specifically the combinational therapy of autophagy modulators with the inhibitors of the NLRP3 inflammasome, antiviral drugs, or anti-inflammatory drugs in the fight against COVID-19.


Subject(s)
COVID-19 , Pneumonia , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/pharmacology , Autophagy , Cytokine Release Syndrome , Humans , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , SARS-CoV-2
10.
Inflammopharmacology ; 30(6): 2003-2016, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2048379

ABSTRACT

Coronavirus disease 2019 (Covid-19) is a global diastrophic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 leads to inflammatory, immunological, and oxidative changes, by which SARS-CoV-2 leads to endothelial dysfunction (ED), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and multi-organ failure (MOF). Despite evidence illustrating that some drugs and vaccines effectively manage and prevent Covid-19, complementary herbal medicines are urgently needed to control this pandemic disease. One of the most used herbal medicines is berberine (BBR), which has anti-inflammatory, antioxidant, antiviral, and immune-regulatory effects; thus, BBR may be a prospective candidate against SARS-CoV-2 infection. This review found that BBR has anti-SARS-CoV-2 effects with mitigation of associated inflammatory changes. BBR also reduces the risk of ALI/ARDS in Covid-19 patients by inhibiting the release of pro-inflammatory cytokines and inflammatory signaling pathways. In conclusion, BBR has potent anti-inflammatory, antioxidant, and antiviral effects. Therefore, it can be utilized as a possible anti-SARS-CoV-2 agent. BBR inhibits the proliferation of SARS-CoV-2 and attenuates the associated inflammatory disorders linked by the activation of inflammatory signaling pathways. Indeed, BBR can alleviate ALI/ARDS in patients with severe Covid-19. In this sense, clinical trials and prospective studies are suggested to illustrate the potential role of BBR in treating Covid-19.


Subject(s)
Berberine , COVID-19 , Respiratory Distress Syndrome , Humans , COVID-19/drug therapy , SARS-CoV-2 , Berberine/pharmacology , Berberine/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Prospective Studies , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
11.
Molecules ; 27(18)2022 Sep 15.
Article in English | MEDLINE | ID: covidwho-2043868

ABSTRACT

Traditionally, Brassica species are widely used in traditional medicine, human food, and animal feed. Recently, special attention has been dedicated to Brassica seeds as source of health-promoting phytochemicals. This review provides a summary of recent research on the Brassica seed phytochemistry, bioactivity, dietary importance, and toxicity by screening the major online scientific database sources and papers published in recent decades by Elsevier, Springer, and John Wiley. The search was conducted covering the period from January 1964 to July 2022. Phytochemically, polyphenols, glucosinolates, and their degradation products were the predominant secondary metabolites in seeds. Different extracts and their purified constituents from seeds of Brassica species have been found to possess a wide range of biological properties including antioxidant, anticancer, antimicrobial, anti-inflammatory, antidiabetic, and neuroprotective activities. These valuable functional properties of Brassica seeds are related to their richness in active compounds responsible for the prevention and treatment of various chronic diseases such as obesity, diabetes, cancer, and COVID-19. Currently, the potential properties of Brassica seeds and their components are the main focus of research, but their toxicity and health risks must also be accounted for.


Subject(s)
Anti-Infective Agents , Brassica , COVID-19 , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Brassica/chemistry , Ethnopharmacology , Glucosinolates , Humans , Hypoglycemic Agents/pharmacology , Phytochemicals/chemistry , Phytochemicals/pharmacology , Phytotherapy , Plant Extracts/chemistry , Seeds
12.
BMC Complement Med Ther ; 22(1): 242, 2022 Sep 17.
Article in English | MEDLINE | ID: covidwho-2043124

ABSTRACT

BACKGROUND: Ecklonia cava is an edible marine brown alga harvested from the ocean that is widely consumed in Asian countries as a health-promoting medicinal food The objective of the present study is to evaluate the anti-asthma mechanism of a new functional food produced by bioprocessing edible algae Ecklonia cava and shiitake Lentinula edodes mushroom mycelia and isolated fractions. METHODS: We used as series of methods, including high performance liquid chromatography, gas chromatography, cell assays, and an in vivo mouse assay to evaluate the asthma-inhibitory effect of Ecklonia cava bioprocessed (fermented) with Lentinula edodes shiitake mushroom mycelium and its isolated fractions in mast cells and in orally fed mice. RESULTS: The treatments inhibited the degranulation of RBL-2H3 cells and immunoglobulin E (IgE) production, suggesting anti-asthma effects in vitro. The in vitro anti-asthma effects in cells were confirmed in mice following the induction of asthma by alumina and chicken egg ovalbumin (OVA). Oral administration of the bioprocessed Ecklonia cava and purified fractions suppressed the induction of asthma and was accompanied by the inhibition of inflammation- and immune-related substances, including eotaxin; thymic stromal lymphopoietin (TSLP); OVA-specific IgE; leukotriene C4 (LTC4); prostaglandin D2 (PGD2); and vascular cell adhesion molecule-1 (VCAM-1) in bronchoalveolar lavage fluid (BALF) and other fluids and organs. Th2 cytokines were reduced and Th1 cytokines were restored in serum, suggesting the asthma-induced inhibitory effect is regulated by the balance of the Th1/Th2 immune response. Serum levels of IL-10, a regulatory T cell (Treg) cytokine, were increased, further favoring reduced inflammation. Histology of lung tissues revealed that the treatment also reversed the thickening of the airway wall and the contraction and infiltration of bronchial and blood vessels and perialveolar inflammatory cells. The bioprocessed Ecklonia cava/mushroom mycelia new functional food showed the highest inhibition as compared with commercial algae and the fractions isolated from the bioprocessed product. CONCLUSIONS: The in vitro cell and in vivo mouse assays demonstrate the potential value of the new bioprocessed formulation as an anti-inflammatory and anti-allergic combination of natural compounds against allergic asthma and might also ameliorate allergic manifestations of foods, drugs, and viral infections.


Subject(s)
Agaricales , Anti-Allergic Agents , Anti-Asthmatic Agents , Asthma , Phaeophyta , Shiitake Mushrooms , Aluminum Oxide/adverse effects , Animals , Anti-Allergic Agents/adverse effects , Anti-Asthmatic Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Asthma/drug therapy , Cytokines/metabolism , Immunoglobulin E , Inflammation/drug therapy , Interleukin-10 , Leukotriene C4/adverse effects , Mice , Mice, Inbred BALB C , Mycelium , Ovalbumin/adverse effects , Phaeophyta/metabolism , Prostaglandin D2/adverse effects , Shiitake Mushrooms/metabolism , Vascular Cell Adhesion Molecule-1/adverse effects
13.
Mar Drugs ; 20(9)2022 Sep 06.
Article in English | MEDLINE | ID: covidwho-2039912

ABSTRACT

Three unusual diterpenes with rare sarsolenane and capnosane skeletons, namely mililatensols A-C (1-3), were isolated from the South China Sea soft coral Sarcophyton mililatensis, leading to the first record of sarsolenane and capnosane diterpenes from the title animal. The structures of compounds 1-3 were established by extensive spectroscopic analysis and comparison with the literature data. Moreover, the absolute configuration of 2 was determined by TDDFT ECD calculations. In an in vitro bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages. In the preliminary virtual screening of inhibitory potential against SARS-CoV-2 by molecular docking, the results showed these three diterpenes were potential SARS-CoV-2 Mpro inhibitors.


Subject(s)
Anthozoa , COVID-19 , Diterpenes , Animals , Anthozoa/chemistry , Anti-Inflammatory Agents/pharmacology , Diterpenes/chemistry , Lipopolysaccharides , Molecular Docking Simulation , Molecular Structure , SARS-CoV-2 , Tumor Necrosis Factor-alpha
14.
Eur J Med Chem ; 241: 114659, 2022 Nov 05.
Article in English | MEDLINE | ID: covidwho-2035972

ABSTRACT

Cytokine storm is a key feature of sepsis and severe stage of COVID-19, and the immunosuppression after excessive immune activation is a substantial hazard to human life. Both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are recognized by various pattern recognition receptors (PRRs), which lead to the immune response. A number of neolignan analogues were synthesized in this work and showed powerful anti-inflammation properties linked to the response to innate and adaptive immunity, as well as NP-7 showed considerable anti-inflammatory activity at 100 nM. On the sepsis model caused by cecum ligation and puncture (CLP) in C57BL/6J mice, NP-7 displayed a strong regulatory influence on cytokine release. Then a photo-affinity probe of NP-7 was synthesized and chemoproteomics based on stable isotope labeling with amino acids in cell cultures (SILAC) identified Immunity-related GTPase M (IRGM) as a target suppressing cytokine storm, which was verified by competitive pull-down, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and molecular dynamics simulations.


Subject(s)
Anti-Inflammatory Agents , Cytokine Release Syndrome , GTP-Binding Proteins , Sepsis , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , COVID-19 , Cytokine Release Syndrome/drug therapy , Cytokines/metabolism , Disease Models, Animal , GTP-Binding Proteins/metabolism , Humans , Mice , Mice, Inbred C57BL , Proteomics
15.
Biomed Pharmacother ; 155: 113666, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2027928

ABSTRACT

Acute lung injury (ALI) and its more serious form; acute respiratory distress syndrome are major causes of COVID-19 related mortality. Finding new therapeutic targets for ALI is thus of great interest. This work aimed to prepare a biocompatible nanoformulation for effective pulmonary delivery of the herbal drug; tanshinone-IIA (TSIIA) for ALI management. A nanoemulsion (NE) formulation based on bioactive natural ingredients; rhamnolipid biosurfactant and tea-tree oil, was developed using a simple ultrasonication technique, optimized by varying oil concentration and surfactant:oil ratio. The selected TSIIA-NE formulation showed 105.7 nm diameter and a PDI âˆ¼ 0.3. EE exceeded 98 % with biphasic sustained drug release and good stability over 3-months. In-vivo efficacy was evaluated in lipopolysaccharide (LPS)-induced ALI model. TSIIA-NE (30 µg/kg) was administered once intratracheally 2 h after LPS instillation. Evaluation was performed 7days post-treatment. Pulmonary function assessment, inflammatory, oxidative stress and glycocalyx shedding markers analysis in addition to histopathological examination of lung tissue were performed. When compared to untreated rats, in-vivo efficacy study demonstrated 1.4 and 1.9-fold increases in tidal volume and minute respiratory volume, respectively, with 32 % drop in wet/dry lung weight ratio and improved levels of arterial blood gases. Lung histopathology and biochemical analysis of different biomarkers in tissue homogenate and bronchoalveolar lavage fluid indicated that treatment may ameliorate LPS-induced ALI symptoms thorough anti-oxidative, anti-inflammatory effects and inhibition of glycocalyx degradation. TSIIA-NE efficacy was superior to free medication and blank-NE. The enhanced efficacy of TSIIA bioactive nanoemulsion significantly suggests the pharmacotherapeutic potential of bioactive TSIIA-NE as a promising nanoplatform for ALI.


Subject(s)
Acute Lung Injury , COVID-19 , Rats , Animals , Lipopolysaccharides/pharmacology , Glycocalyx/pathology , COVID-19/drug therapy , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Acute Lung Injury/pathology , Lung , Anti-Inflammatory Agents/pharmacology , Surface-Active Agents/pharmacology , Gases/adverse effects , Gases/metabolism , Tea/metabolism
16.
Int J Mol Sci ; 23(18)2022 Sep 07.
Article in English | MEDLINE | ID: covidwho-2010122

ABSTRACT

Inhibition of inflammatory responses from the spike glycoprotein of SARS-CoV-2 (Spike) by targeting NLRP3 inflammasome has recently been developed as an alternative form of supportive therapy besides the traditional anti-viral approaches. Clerodendrum petasites S. Moore (C. petasites) is a Thai traditional medicinal plant possessing antipyretic and anti-inflammatory activities. In this study, C. petasites ethanolic root extract (CpEE) underwent solvent-partitioned extraction to obtain the ethyl acetate fraction of C. petasites (CpEA). Subsequently, C. petasites extracts were determined for the flavonoid contents and anti-inflammatory properties against spike induction in the A549 lung cells. According to the HPLC results, CpEA significantly contained higher amounts of hesperidin and hesperetin flavonoids than CpEE (p < 0.05). A549 cells were then pre-treated with either C. petasites extracts or its active flavonoids and were primed with 100 ng/mL of spike S1 subunit (Spike S1) and determined for the anti-inflammatory properties. The results indicate that CpEA (compared with CpEE) and hesperetin (compared with hesperidin) exhibited greater anti-inflammatory properties upon Spike S1 induction through a significant reduction in IL-6, IL-1ß, and IL-18 cytokine releases in A549 cells culture supernatant (p < 0.05). Additionally, CpEA and hesperetin significantly inhibited the Spike S1-induced inflammatory gene expressions (NLRP3, IL-1ß, and IL-18, p < 0.05). Mechanistically, CpEA and hesperetin attenuated inflammasome machinery protein expressions (NLRP3, ASC, and Caspase-1), as well as inactivated the Akt/MAPK/AP-1 pathway. Overall, our findings could provide scientific-based evidence to support the use of C. petasites and hesperetin in the development of supportive therapies for the prevention of COVID-19-related chronic inflammation.


Subject(s)
Antipyretics , COVID-19 , Clerodendrum , Hesperidin , Petasites , A549 Cells , Anti-Inflammatory Agents/pharmacology , COVID-19/drug therapy , Caspase 1/metabolism , Clerodendrum/metabolism , Cytokines/metabolism , Flavonoids/pharmacology , Hesperidin/pharmacology , Humans , Inflammasomes/metabolism , Interleukin-18 , Interleukin-6 , Lung/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-akt , SARS-CoV-2 , Solvents , Spike Glycoprotein, Coronavirus , Transcription Factor AP-1
17.
Int J Mol Sci ; 23(17)2022 Sep 04.
Article in English | MEDLINE | ID: covidwho-2010115

ABSTRACT

Background: Hyperinflammation is frequently associated with the chronic pain of autoimmune disease and the acute death of coronavirus disease (COVID-19) via a severe cytokine cascade. CIGB-258 (Jusvinza®), an altered peptide ligand with 3 kDa from heat shock protein 60 (HSP60), inhibits the systemic inflammation and cytokine storm, but the precise mechanism is still unknown. Objective: The protective effect of CIGB-258 against inflammatory stress of N-ε-carboxymethyllysine (CML) was tested to provide mechanistic insight. Methods: CIGB-258 was treated to high-density lipoproteins (HDL) and injected into zebrafish and its embryo to test a putative anti-inflammatory activity under presence of CML. Results: Treatment of CML (final 200 µM) caused remarkable glycation of HDL with severe aggregation of HDL particles to produce dysfunctional HDL, which is associated with a decrease in apolipoprotein A-I stability and lowered paraoxonase activity. Degradation of HDL3 by ferrous ions was attenuated by a co-treatment with CIGB-258 with a red-shift of the Trp fluorescence in HDL. A microinjection of CML (500 ng) into zebrafish embryos resulted in the highest embryo death rate, only 18% of survivability with developmental defects. However, co-injection of CIGB-258 (final 1 ng) caused the remarkable elevation of survivability around 58%, as well as normal developmental speed. An intraperitoneal injection of CML (final 250 µg) into adult zebrafish resulted acute paralysis, sudden death, and laying down on the bottom of the cage with no swimming ability via neurotoxicity and inflammation. However, a co-injection of CIGB-258 (1 µg) resulted in faster recovery of the swimming ability and higher survivability than CML alone injection. The CML alone group showed 49% survivability, while the CIGB-258 group showed 97% survivability (p < 0.001) with a remarkable decrease in hepatic inflammation up to 50%. A comparison of efficacy with CIGB-258, Infliximab (Remsima®), and Tocilizumab (Actemra®) showed that the CIGB-258 group exhibited faster recovery and swimming ability with higher survivability than those of the Infliximab group. The CIGB-258 group and Tocilizumab group showed the highest survivability, the lowest plasma total cholesterol and triglyceride level, and the infiltration of inflammatory cells, such as neutrophils in hepatic tissue. Conclusion: CIGB-258 ameliorated the acute neurotoxicity, paralysis, hyperinflammation, and death induced by CML, resulting in higher survivability in zebrafish and its embryos by enhancing the HDL structure and functionality.


Subject(s)
COVID-19 , Lipoproteins, HDL , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Inflammation/drug therapy , Infliximab , Lysine/analogs & derivatives , Paralysis , Zebrafish/metabolism
18.
Biomed Pharmacother ; 154: 113625, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2003886

ABSTRACT

The Coronavirus Disease-2019 (COVID-19) pandemic urges researching possibilities for prevention and management of the effects of the virus. Carotenoids are natural phytochemicals of anti-oxidant, anti-inflammatory and immunomodulatory properties and may exert potential in aiding in combatting the pandemic. This review presents the direct and indirect evidence of the health benefits of carotenoids and derivatives based on in vitro and in vivo studies, human clinical trials and epidemiological studies and proposes possible mechanisms of action via which carotenoids may have the capacity to protect against COVID-19 effects. The current evidence provides a rationale for considering carotenoids as natural supportive nutrients via antioxidant activities, including scavenging lipid-soluble radicals, reducing hypoxia-associated superoxide by activating antioxidant enzymes, or suppressing enzymes that produce reactive oxygen species (ROS). Carotenoids may regulate COVID-19 induced over-production of pro-inflammatory cytokines, chemokines, pro-inflammatory enzymes and adhesion molecules by nuclear factor kappa B (NF-κB), renin-angiotensin-aldosterone system (RAS) and interleukins-6- Janus kinase-signal transducer and activator of transcription (IL-6-JAK/STAT) pathways and suppress the polarization of pro-inflammatory M1 macrophage. Moreover, carotenoids may modulate the peroxisome proliferator-activated receptors γ by acting as agonists to alleviate COVID-19 symptoms. They also may potentially block the cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human angiotensin-converting enzyme 2 (ACE2). These activities may reduce the severity of COVID-19 and flu-like diseases. Thus, carotenoid supplementation may aid in combatting the pandemic, as well as seasonal flu. However, further in vitro, in vivo and in particular long-term clinical trials in COVID-19 patients are needed to evaluate this hypothesis.


Subject(s)
COVID-19 , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , COVID-19/drug therapy , Carotenoids/pharmacology , Carotenoids/therapeutic use , Humans , Pandemics , SARS-CoV-2
19.
Mediators Inflamm ; 2022: 7138756, 2022.
Article in English | MEDLINE | ID: covidwho-2001956

ABSTRACT

Resveratrol is a naturally occurring stilbene phytoalexin phenolic compound, which has been extensively studied on its biological activity. It has been widely accepted that resveratrol possesses anti-inflammatory and antiviral activities. In this review, we summarize the anti-inflammatory dosages and mechanism and antiviral mechanism of resveratrol. Since viral infections are often accompanied by inflammation, we propose that the NF-κB signaling pathway is a key and common molecular mechanism of resveratrol to exert anti-inflammatory and antiviral effects. For future studies, we believe that resveratrol's anti-inflammatory and antiviral mechanisms can consider the upstream signaling molecules of the NF-κB signaling pathway. For resveratrol antivirus, future studies can be conducted on the interaction of resveratrol with key proteins or important enzymes of the virus. In addition, we also think that the clinical application of resveratrol is very important. In short, resveratrol is a promising anti-inflammatory and antiviral drug, and research on it needs to be expanded.


Subject(s)
NF-kappa B , Stilbenes , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , NF-kappa B/metabolism , Resveratrol , Stilbenes/pharmacology , Stilbenes/therapeutic use
20.
Drug Des Devel Ther ; 16: 2479-2495, 2022.
Article in English | MEDLINE | ID: covidwho-1993629

ABSTRACT

Background: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas without specific treatment. Shenmai injection (SMI) was reported to eliminate the severity of experimental AP. This study aimed to explore the mechanisms underlying the synergistic protective effects of SMI on AP based on network pharmacology and experimental validation. Methods: Network pharmacology analysis and molecular docking based on identified components were performed to construct the potential therapeutic targets and pathways. The principal components of SMI were detected via ultra-high-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Effect of SMI and the identified components on cellular injury and IL6/STAT3 signaling was assessed on mouse pancreatic acinar cell line 266-6 cells. Finally, 4% sodium taurocholate (NaT) was used to induce AP model to assess the effects of SMI in treating AP and validate the potential molecular mechanisms. Results: By searching the TCMSP and ETCM databases, 119 candidate components of SMI were obtained. UHPLC-QTOF/MS analysis successfully determined the representative components of SMI: ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D. Fifteen hub targets and eight related pathways were obtained to establish the main pharmacology network. Subnetwork analysis and molecular docking indicated that the effects of these four main SMI components were mostly related to the interleukin (IL) 6/STAT3 pathway. In vitro, SMI, ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D increased the cell viability of NaT-stimulated mouse pancreatic acinar 266-6 cells and decreased IL6 and STAT3 expression. In vivo, 10 mL/kg SMI significantly alleviated the pancreatic histopathological changes and the expression of IL6 and STAT3 in the AP mice. Conclusion: This study demonstrated SMI may exert anti-inflammatory effects against AP by suppressing IL6/STAT3 activation, thus providing a basis for its potential use in clinical practice and further study in treating AP.


Subject(s)
Drugs, Chinese Herbal , Pancreatitis , Acute Disease , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Drug Combinations , Interleukin-6 , Mice , Molecular Docking Simulation , Network Pharmacology , Pancreatitis/metabolism
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