scholarly journals Calcio-Herbal Medicine Divya-Swasari-Vati Ameliorates SARS-CoV-2 Spike Protein-Induced Pathological Features and Inflammation in Humanized Zebrafish Model by Moderating IL-6 and TNF-α Cytokines

2020 ◽  
Vol Volume 13 ◽  
pp. 1219-1243
Author(s):  
Acharya Balkrishna ◽  
Sudeep Verma ◽  
Siva Kumar Solleti ◽  
Lakshmipathi Khandrika ◽  
Anurag Varshney
Keyword(s):  
Herbal Medicine ◽  
Spike Protein ◽  
Pathological Features ◽  
Zebrafish Model ◽  
Tnf Α

scholarly journals Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5091
Author(s):  
Acharya Balkrishna ◽  
Siva Kumar Solleti ◽  
Sudeep Verma ◽  
Anurag Varshney
Keyword(s):  
Herbal Medicine ◽  
High Performance ◽  
Normal Skin ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Spike Protein ◽  
Protective Effects ◽  
Cell Degeneration ◽  
Zebrafish Model ◽  
Tnf Α

Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV–V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1β induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.

scholarly journals Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

2017 ◽  
Vol 43 (5) ◽  
pp. 2074-2087 ◽  
Author(s):  
Liling Yang ◽  
Xiangjun Zhou ◽  
Weijuan Huang ◽  
Qin Fang ◽  
Jianlan Hu ◽  
...  
Keyword(s):  
Signalling Pathway ◽  
Dependent Manner ◽  
Zebrafish Model ◽  
Lps Challenge ◽  
Cell Counts ◽  
Tnf Α ◽  
Forsythia Suspensa ◽  
Anti Inflammatory

Background/Aims: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF-α expression. Conclusion: This study provides a rationale for the clinical application of PHN as an anti-inflammatory agent.

scholarly journals Effects of Toosendanin on Pregnancy and Uterine Immunity Alterations in Mice

2010 ◽  
Vol 38 (02) ◽  
pp. 319-328 ◽  
Author(s):  
Jian-Lou Zhang ◽  
Wang-Yu Shi ◽  
Wei Zhong ◽  
Ai-Tuan Ma ◽  
Xiao-Dan Wang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Herbal Medicine ◽  
Chinese Herbal Medicine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chinese Herbal ◽  
Cd8 T Lymphocytes ◽  
Tnf Α ◽  
Ifn Γ ◽  
Th1 Cytokines ◽  
Dose Dependent

This study was conducted to explore the abortifacient effect and the mechanisms of the Chinese herbal medicine component toosendanin, and to elucidate the significance of the Th1 cytokines IFN-γ and TNF-α, CD4+ and CD8+ T lymphocytes in the occurrence of abortion. Graded doses of toosendanin were given by intraperitoneal injection (i.p.) to mice at day 5, 6, 7 of gestation. The levels of Th1 cytokines (IFN-γ, TNF-α) in serum and uterine tissues from mice sacrificed at day 8 were analyzed by enzyme linked immunosorbent assay (ELISA). Presence of T lymphocytes in endometrium was detected by immunohistochemistry. The results revealed that injection of toosendanin could produce a dose-dependent toxicity. The IFN-γ, TNF-α content in serum and uterine tissues were increased significantly. The CD4+ and CD8+ T lymphocytes were also increased in the endometrium of toosendanin treated groups. In conclusion, toosendanin is pregnancy-toxic to animals and it is relevant to the increased contents of IFN-γ, TNF-α and CD4+, CD8+ T lymphocytes.

scholarly journals SARS-CoV-2 Spike Protein S1-Mediated Endothelial Injury and Pro-Inflammatory State Is Amplified by Dihydrotestosterone and Prevented by Mineralocorticoid Antagonism

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2209
Author(s):  
Nitin Kumar ◽  
Yu Zuo ◽  
Srilakshmi Yalavarthi ◽  
Kristina L. Hunker ◽  
Jason S. Knight ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Activation ◽  
Endothelial Injury ◽  
Spike Protein ◽  
Severe Illness ◽  
Therapeutic Effects ◽  
Vascular Effects ◽  
Adjunct Treatment ◽  
Tnf Α

Men are disproportionately affected by the coronavirus disease-2019 (COVID-19), and face higher odds of severe illness and death compared to women. The vascular effects of androgen signaling and inflammatory cytokines in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-mediated endothelial injury are not defined. We determined the effects of SARS-CoV-2 spike protein-mediated endothelial injury under conditions of exposure to androgen dihydrotestosterone (DHT) and tumor necrosis factor-a (TNF-α) and tested potentially therapeutic effects of mineralocorticoid receptor antagonism by spironolactone. Circulating endothelial injury markers VCAM-1 and E-selectin were measured in men and women diagnosed with COVID-19. Exposure of endothelial cells (ECs) in vitro to DHT exacerbated spike protein S1-mediated endothelial injury transcripts for the cell adhesion molecules E-selectin, VCAM-1 and ICAM-1 and anti-fibrinolytic PAI-1 (p < 0.05), and increased THP-1 monocyte adhesion to ECs (p = 0.032). Spironolactone dramatically reduced DHT+S1-induced endothelial activation. TNF-α exacerbated S1-induced EC activation, which was abrogated by pretreatment with spironolactone. Analysis from patients hospitalized with COVID-19 showed concordant higher circulating VCAM-1 and E-Selectin levels in men, compared to women. A beneficial effect of the FDA-approved drug spironolactone was observed on endothelial cells in vitro, supporting a rationale for further evaluation of mineralocorticoid antagonism as an adjunct treatment in COVID-19.

scholarly journals SARS-CoV-2 Spike Glycoprotein S1 Induces Neuroinflammation in BV-2 Microglia

2021 ◽  
Author(s):  
Olumayokun A. Olajide ◽  
Victoria U. Iwuanyanwu ◽  
Oyinkansola D. Adegbola ◽  
Alaa A. Al-Hindawi
Keyword(s):  
P38 Mapk ◽  
Transcriptional Activity ◽  
Immunofluorescence Microscopy ◽  
Spike Protein ◽  
Respiratory Complications ◽  
Protein Levels ◽  
Tnf Α ◽  
Tlr4 Activation ◽  
Interfering Rna ◽  
Culture Supernatants

AbstractIn addition to respiratory complications produced by SARS‐CoV‐2, accumulating evidence suggests that some neurological symptoms are associated with the disease caused by this coronavirus. In this study, we investigated the effects of the SARS‐CoV‐2 spike protein S1 stimulation on neuroinflammation in BV-2 microglia. Analyses of culture supernatants revealed an increase in the production of TNF-α, IL-6, IL-1β and iNOS/NO. S1 also increased protein levels of phospho-p65 and phospho-IκBα, as well as enhanced DNA binding and transcriptional activity of NF-κB. These effects of the protein were blocked in the presence of BAY11-7082 (1 µM). Exposure of S1 to BV-2 microglia also increased the protein levels of NLRP3 inflammasome and enhanced caspase-1 activity. Increased protein levels of p38 MAPK was observed in BV-2 microglia stimulated with the spike protein S1 (100 ng/ml), an action that was reduced in the presence of SKF 86,002 (1 µM). Results of immunofluorescence microscopy showed an increase in TLR4 protein expression in S1-stimulated BV-2 microglia. Furthermore, pharmacological inhibition with TAK 242 (1 µM) and transfection with TLR4 small interfering RNA resulted in significant reduction in TNF-α and IL-6 production in S1-stimulated BV-2 microglia. These results have provided the first evidence demonstrating S1-induced neuroinflammation in BV-2 microglia. We propose that induction of neuroinflammation by this protein in the microglia is mediated through activation of NF-κB and p38 MAPK, possibly as a result of TLR4 activation. These results contribute to our understanding of some of the mechanisms involved in CNS pathologies of SARS-CoV-2.

scholarly journals Study on Anti-Inflammatory Effect and Major Anti-Inflammatory Components of PSORI-CM02 by Zebrafish Model

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiaohong Yuan ◽  
Leyu Huang ◽  
Jiaqi Lei ◽  
Yingxin Long ◽  
Cong Li
Keyword(s):  
Chinese Medicine ◽  
Herbal Medicine ◽  
Critical Role ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Macrophage Phagocytosis ◽  
The Common ◽  
Multiple Component ◽  
Anti Inflammatory

PSORI-CM02 is an optimization formula of PSORI-CM01, which is a clinical herbal formula for the treatment for psoriasis in the Guangdong Provincial Hospital of Chinese Medicine. Previous research indicates that it plays a critical role in anti-inflammation and immunoregulation. Rhizoma smilacis glabrae (RSG) is one herbal medicine of PSORI-CM02, whose effective anti-inflammatory component is astilbin. This study aims to test the anti-inflammatory and immunoregulation effects of astilbin as well as RSG in PSORI-CM02, and we, respectively, used the CuSO4-induced neutrophil-specific transgenic zebrafish model Tg(mpx: EGFP) and the melanin allele mutated Albino strain zebrafish model to visualize the effects of neutrophil recruitment and macrophage phagocytosis. Our data indicated that both PSORI-CM02 and astilbin had anti-inflammatory effects, leading to a reduction in the recruitment of neutrophils and promotion in macrophage phagocytosis. Nevertheless, the negative liquor of Rhizoma smilacis glabrae (PSORI-CM02 without RSG) also had anti-inflammatory and promoting macrophage phagocytosis effects. The results revealed the formula excluding RSG also had anti-inflammatory and immunoregulation effects, which demonstrated that RSG was not the major anti-inflammatory herbal medicine in PSORI-CM02. Similarly, astilbin was not the major anti-inflammatory active ingredient in the formula. The anti-inflammatory and the promotion of macrophage phagocytosis effect of PSORI-CM02 in vivo zebrafish were the results of multiple component interaction, which was the common characteristic of the Chinese medicine compound.

scholarly journals Up-regulation of IL-6 and TNF-α induced by SARS-coronavirus spike protein in murine macrophages via NF-κB pathway

2007 ◽  
Vol 128 (1-2) ◽  
pp. 1-8 ◽  
Author(s):  
Wei Wang ◽  
Linbai Ye ◽  
Li Ye ◽  
Baozong Li ◽  
Bo Gao ◽  
...  
Keyword(s):  
Spike Protein ◽  
Sars Coronavirus ◽  
Murine Macrophages ◽  
Tnf Α

Macrophage-Mediated Inhibitory Effect ofZingiber officinaleRosc, A Traditional Oriental Herbal Medicine, on the Growth of Influenza A/Aichi/2/68 Virus

2006 ◽  
Vol 34 (01) ◽  
pp. 157-169 ◽  
Author(s):  
Nobuko Imanishi ◽  
Tsugunobu Andoh ◽  
Naoki Mantani ◽  
Shinya Sakai ◽  
Katsutoshi Terasawa ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Influenza A ◽  
Mdck Cells ◽  
Zingiber Officinale ◽  
Inhibitory Effect ◽  
Aichi Virus ◽  
Tnf Α ◽  
Infected Cells ◽  
Necrosis Factor ◽  
Darby Canine Kidney

The inhibitory effect of Zingiber officinale Rosc (ZOR), an Oriental traditional herbal medicine, on the growth of influenza A/Aichi/2/68 (Aichi) virus was investigated in Madin-Darby canine kidney (MDCK) cells. Direct addition of ZOR (0.1 ~ 100 μ g/ml ) to the infected cells did not have any inhibitory effect. However, the ZOR-induced conditioned medium (ZOR-CM) of RAW cells, a murine macrophage (Mφ) cell line, exhibited an apparent inhibitory effect on MDCK cells without cytotoxicity. In accordance with the time-dependent inhibitory effect of ZOR-CM, it has been demonstrated that tumor necrosis factor (TNF)-α was gradually accumulated in ZOR-CM by the induction of TNF-α mRNA expression in ZOR-stimulated RAW cells. Conversely, the inhibitory effect of ZOR-CM was reduced significantly by the removal of TNF-α after the formation of an immune complex with anti-TNF-α monoclonal antibody. These data suggested that ZOR itself has no inhibitory effect on the growth of influenza virus, but could exert its effect via macrophage activation leading to production of TNF-α.

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