scholarly journals A cannabinoid receptor agonist shows anti-inflammatory and survival properties in human SARS-CoV-2-infected iPSC-derived cardiomyocytes

2021 ◽  
Author(s):  
Luiz Guilherme H. S. Aragão ◽  
Júlia T. Oliveira ◽  
Jairo R. Temerozo ◽  
Mayara A. Mendes ◽  
José Alexandre Salerno ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
List Type ◽  
Protective Effects ◽  
Cardiac Damage ◽  
Necrosis Factor Alpha ◽  
Risk Of Mortality ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Human Ipsc

AbstractCoronavirus disease 2019 (COVID-19) is caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs and lead to loss of vital organ function, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, caused both directly and indirectly by SARS-CoV-2, and which is associated with a high risk of mortality. One of the hallmarks of severe COVID-19 is the “cytokine storm”, at which point the immune system malfunctions, leading to possible organ failure and death. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) on SARS-CoV-2-infected human iPSC-derived cardiomyocytes (hiPSC-CMs). Although WIN did not modulate angiotensin-converting enzyme II, nor reduced SARS-CoV-2 infection and replication in hiPSC-CMs at the conditions tested, it had anti-inflammatory and protective effects by reducing the levels of interleukins 6, 8,18 and tumor necrosis factor-alpha (TNF-α) and lactate dehydrogenase (LDH) activity in these cells without causing hypertrophic cardiac damage. These findings suggest that cannabinoids should be further investigated as an alternative therapeutic tool for the treatment of COVID-19.HighlightsHuman iPSC-derived cardiomyocytes (hiPSC-CMs) express CB1 receptor.The cannabinoid receptor agonist, WIN 55,212-2 (WIN), does not influence SARS-CoV-2 infection in hiPSC-CMs.WIN reduces inflammation and death in SARS-CoV-2-infected hiPSC-CMs.

scholarly journals WIN 55,212-2 shows anti-inflammatory and survival properties in human iPSC-derived cardiomyocytes infected with SARS-CoV-2

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12262
Author(s):  
Luiz Guilherme H. S. Aragão ◽  
Júlia T. Oliveira ◽  
Jairo R. Temerozo ◽  
Mayara A. Mendes ◽  
José Alexandre Salerno ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Heart Tissue ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Risk Of Mortality ◽  
Inflammatory Processes ◽  
Infected Cells ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Human Ipsc

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that lead to damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the “cytokine storm”, strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins six, eight, 18 and tumor necrosis factor-alpha (TNF-α) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.

scholarly journals Extracts from Fermented Black Garlic Exhibit a Hepatoprotective Effect on Acute Hepatic Injury

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1112 ◽  
Author(s):  
Jen-Chieh Tsai ◽  
Yi-An Chen ◽  
Jung-Tsung Wu ◽  
Kuan-Chen Cheng ◽  
Ping-Shan Lai ◽  
...  
Keyword(s):  
Hepatic Injury ◽  
Interleukin 1 ◽  
Water Layer ◽  
Hepatoprotective Effect ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Acute Hepatic Injury ◽  
Factor Alpha ◽  
Anti Inflammatory

The mechanism of hepatoprotective compounds is usually related to its antioxidant or anti-inflammatory effects. Black garlic is produced from garlic by heat treatment and its anti-inflammatory activity has been previously reported. Therefore, the aim of this study was to investigate the hepatoprotective effect of five different extracts of black garlic against carbon tetrachloride (CCl4)-induced acute hepatic injury (AHI). In this study, mice in the control, CCl4, silymarin, and black garlic groups were orally administered distilled water, silymarin, and different fraction extracts of black garlic, respectively, after CCl4 was injected intraperitoneally to induce AHI. The results revealed that the n-butanol layer extract (BA) and water layer extract (WS) demonstrated a hepatoprotective effect by reducing the levels of alanine aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and hepatic malondialdehyde (MDA). Furthermore, the BA and WS fractions of black garlic extract increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), tumor necrosis factor alpha (TNF-α), and the interleukin-1 (IL-1β) level in liver. It was concluded that black garlic exhibited significant protective effects on CCl4-induced acute hepatic injury.

scholarly journals Anti-Neuroinflammatory and Anti-Inflammatory Activities of Phenylheptatriyne Isolated from the Flowers of Coreopsis lanceolata L. via NF-κB Inhibition and HO-1 Expression in BV2 and RAW264.7 Cells

2021 ◽  
Vol 22 (14) ◽  
pp. 7482
Author(s):  
Hwan Lee ◽  
Zhiming Liu ◽  
Chi-Su Yoon ◽  
Linsha Dong ◽  
Wonmin Ko ◽  
...  
Keyword(s):  
Silica Gel ◽  
Column Chromatography ◽  
Raw264.7 Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Etoac Fraction ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
And Oxidative Stress ◽  
Necrosis Factor

Aging is associated with immune disregulation and oxidative stress which lead to inflammation and neurodegenerative diseases. We have tried to identify the anti-neuroinflammatory and anti-inflammatory components of Coreopsis lanceolata L. The dried flowers of C. lanceolata were extracted with 70% EtOH, and the obtained extract was divided into CH2Cl2, EtOAc, n-BuOH, and H2O fractions. The CH2Cl2 fraction was separated using silica gel and C-18 column chromatography to yield phenylheptatriyne (1), 2′-hydroxy-3,4,4′-trimethoxychalcone (2), and 4′,7-dimethoxyflavanone (3). Additionally, the EtOAc fraction was subjected to silica gel, C-18, and Sephadex LH-20 column chromatography to yield 8-methoxybutin (4) and leptosidin (5). All the compounds isolated from C. lanceolata inhibited the production of nitric oxide (NO) in LPS-induced BV2 and RAW264.7 cells. In addition, phenylheptatriyne and 4′,7-dimethoxyflavanone reduced the secretion of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6. Among them, phenylheptatriyne was significantly downregulated in the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequently, phenylheptatriyne also effectively inhibited nuclear factor-kappa B (NF-κB) activation in LPS-stimulated BV2 and RAW264.7 cells. Based on these results, the anti-neuroinflammatory effect of phenylheptatriyne isolated from C. lanceolata was confirmed, which may exert a therapeutic effect in treatment of neuroinflammation-related diseases.

scholarly journals A Novel Curcumin-Mycophenolic Acid Conjugate Inhibited Hyperproliferation of Tumor Necrosis Factor-Alpha-Induced Human Keratinocyte Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 956
Author(s):  
Yonelian Yuyun ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Wiwat Supasena ◽  
Piyapan Suwattananuruk ◽  
Kemika Praengam ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Mycophenolic Acid ◽  
Tumor Necrosis ◽  
Molecular Mechanisms ◽  
Cellular Transport ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Curcumin (CUR) has been used as adjuvant therapy for therapeutic application in the treatment of psoriasis through several mechanisms of action. Due to the poor oral bioavailability of CUR, several approaches have been developed to overcome the limitations of CUR, including the prodrug strategy. In this study, CUR was esterified with mycophenolic acid (MPA) as a novel conjugate prodrug. The MPA-CUR conjugate was structurally elucidated using FT-IR, 1H-NMR, 13C-NMR, and MS techniques. Bioavailable fractions (BFs) across Caco-2 cells of CUR, MPA, and MPA-CUR were collected for further biological activity evaluation representing an in vitro cellular transport model for oral administration. The antipsoriatic effect of the BFs was determined using antiproliferation and anti-inflammation assays against hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced human keratinocytes (HaCaT). The BF of MPA-CUR provided better antiproliferation than that of CUR (p < 0.001). The enhanced hyperproliferation suppression of the BF of MPA-CUR resulted from the reduction of several inflammatory cytokines, including IL-6, IL-8, and IL-1β. The molecular mechanisms of anti-inflammatory activity were mediated by an attenuated signaling cascade of MAPKs protein, i.e., p38, ERK, and JNK. Our results present evidence for the MPA-CUR conjugate as a promising therapeutic agent for treating psoriasis by antiproliferative and anti-inflammatory actions.

scholarly journals Hyaluronic Acid-Modified and TPCA-1-Loaded Gold Nanocages Alleviate Inflammation

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 143 ◽  
Author(s):  
Jingnan Zhao
Keyword(s):  
Hyaluronic Acid ◽  
Inflammatory Cells ◽  
Oxygen Species ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Nanogold Particles ◽  
Gold Nanocages ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Gold nanocages (AuNCs) are biocompatible and porous nanogold particles that have been widely used in biomedical fields. In this study, hyaluronic acid (HA) and peptide- modified gold nanocages (HA-AuNCs/T/P) loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) were prepared to investigate their potential for combating inflammation. TPCA-1 was released from AuNCs, intracellularly when HA was hydrolyzed by hyaluronidase. HA-AuNCs/T/P show a much higher intracellular uptake than AuNCs/T/P, and exhibit a much higher efficacy on the suppression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) than free TPCA-1, suggesting great improvement to the anti-inflammatory efficacy of TPCA-1 through the application of AuNCs. HA-AuNCs/T/P can also reduce the production of reactive oxygen species in inflammatory cells. This study suggests that HA-AuNCs/T/P may be potential agents for anti-inflammatory treatment, and are worthy of further investigation.

scholarly journals N-Acetylcysteine (NAC): Impacts on Human Health

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 967
Author(s):  
Micaely Cristina dos Santos Tenório ◽  
Nayara Gomes Graciliano ◽  
Fabiana Andréa Moura ◽  
Alane Cabral Menezes de Oliveira ◽  
Marília Oliveira Fonseca Goulart
Keyword(s):  
Human Health ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Primary Role ◽  
Necrosis Factor Alpha ◽  
Biochemical Basis ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

scholarly journals Suppression of tumor necrosis factor-alpha-induced neutrophil adherence responses by essential oils

2003 ◽  
Vol 12 (6) ◽  
pp. 323-328 ◽  
Author(s):  
Shigeru Abe ◽  
Naho Maruyama ◽  
Kazumi Hayama ◽  
Hiroko Ishibashi ◽  
Shigeharu Inoue ◽  
...  
Keyword(s):  
Essential Oils ◽  
Tumor Necrosis ◽  
Neutrophil Activation ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Neutrophil Adherence ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Background:In aromatherapy, essential oils are used as anti-inflammatory remedies, but experimental studies on their action mechanisms are very limited.Aims:To assess their anti-inflammatory activities, effects of essential oils on neutrophil activation were examinedin vitro.Methods:Neutrophil activation was measured by tumor necrosis factor-alpha (TNF-α)-induced adherence reaction of human peripheral neutrophils.Results:All essential oils tested at 0.1% concentration suppressed TNF-α-induced neutrophil adherence, and, in particular, lemongrass, geranium and spearmint oils clearly lowered the reaction even at 0.0125%. Similar inhibitory activities for the neutrophil adherence were obtained by their major constituent terpenoids: citral, geraniol, citronellol and carvone. In contrast, very popular essential oils, tea tree oil and lavender oil, did not display the inhibitory activity at the concentration.Conclusion:Thus, some essential oils used as anti-inflammatory remedies suppress neutrophil activation by TNF-α at a low concentration (0.0125-0.025%)in vitro.

scholarly journals Local and systemic influence of toxic levels of airborne ozone on the inflammatory response in rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Małgorzata Chmielewska-Krzesińska ◽  
Krzysztof Wąsowicz
Keyword(s):  
Inflammatory Response ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Necrosis Factor Alpha ◽  
Genes Expression ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Abstract Introduction Ozone is not harmful itself; however, it directly oxidises biomolecules and produces radical-dependent cytotoxicity. Exposure to ozone is by inhalation and therefore the lungs develop the main anti-inflammatory response, while ozone has an indirect impact on the other organs. This study investigated the local and systemic effects of the ozone-associated inflammatory response. Material and Methods Three groups each of 5 Wistar Han rats aged 6 months were exposed for 2h to airborne ozone at 0.5 ppm and a fourth identical group were unexposed controls. Sacrifice was at 3h after exposure for control rats and one experimental group and at 24 h and 48 h for the others. Lung and liver samples were evaluated for changes in expression of transforming growth factor beta 1, anti-inflammatory interleukin 10, pro-inflammatory tumour necrosis factor alpha and interleukin 1 beta and two nuclear factor kappa-light-chain-enhancer of B cells subunit genes. Total RNA was isolated from the samples in spin columns and cDNA was synthesised in an RT-PCR. Expression levels were compared to those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and analysed statistically. Results All variables changed non-linearly over time comparing experimental groups to the control. Conspicuous expression changes in the subunit genes and cytokines were observed in both evaluated organs. Conclusion Locally and systemically, inflammation responses to ozone inhalation include regulation of certain genes’ expression. The mechanisms are unalike in lungs and liver but ozone exerts a similar effect in both organs. A broader range of variables influential on ozone response should be studied in the future.

scholarly journals INHIBITORY EFFECTS ON TUMOR NECROSIS FACTOR ALPHA AND INTERLEUKIN 12 USING CLOBETASOL PROPIONATE LOADED TEA TREE OIL NANOEMULSION GEL ON ANIMAL MODEL

2018 ◽  
Vol 11 (6) ◽  
pp. 182
Author(s):  
Md Sarfaraz Alam ◽  
Mohamammad Daud Ali ◽  
Md Salahuddin Ansari ◽  
Pankaj Sharma
Keyword(s):  
Clobetasol Propionate ◽  
Interleukin 12 ◽  
Tea Tree Oil ◽  
Necrosis Factor Alpha ◽  
Tea Tree ◽  
Tnf Α ◽  
Nanoemulsion Gel ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Objective: The main objective of our study is to explore anti-inflammatory activity at its molecular level like tumor necrosis factor alpha (TNF-α), interleukin 12 (IL-12) expression, and histopathological study.Methods: As per solubility/miscibility of clobetasol propionate (CP) with tea tree oil (TTO), surfactant and cosurfactant (Smix), and water in a ratio of oil:Smix:water (15:35:50) taken in milliliter for the preparation of nanoemulsion. Induced allergic contact dermatitis (ACD) with dinitrofluorobenzene (DNFB) was used for the study. TNF-α and interleukin 12 (IL-12) were estimated with rabbit antimouse TNF-α and rat antimouse IL-12 antibodies in 1% of bovine serum albumin in phosphate buffer.Results: Topical application of CP loaded nanoemulsion gel inhibits ear inflammation and erythema in DNFB-induced ACD in mice and significantly reduces the intracellular edema and infiltration with inflammatory mediator cells involving of mononuclear cells and neutrophils. CP loaded nanoemulsion gel reduces expression of protein level of TNF-α and IL-12.Conclusion: CP loaded nanoemulsion gel confirmed that anti-inflammatory effects showed more rapidly than the placebo and marketed gel preparation. However, the animals treated with placebo nanoemulsion gel showed a somehow comparable reduction of their inflammation during treatment compared with the marketed gel. This effect may be due to anti-inflammatory effect of TTO. This result suggested that anti-inflammatory activity of placebo nanoemulsion gel may be due to TTO present in nanoemulsion as vehicle.

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