β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling

Zhou, Beixian; Li, Jing; Liang, Xiaoli; Pan, Xiping; Hao, Yanbing; Xie, Peifang; Jiang, Haiming; Yang, Zifeng; Zhong, Nanshan

doi:10.1038/s41401-020-0403-9

Cited by 47 publications

(36 citation statements)

References 88 publications

(111 reference statements)

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“…The mechanism may be related to the targeting of NETs through NADPH/ROS network signaling [70] . β-sitosterol exhibited a dose-dependent inhibition of in ammatory responses in in uenza A virus -infected cells via NF-κB and p38MAPK signaling [71] .…”

Section: Discussionmentioning

confidence: 96%

WITHDRAWN: Network Pharmacology and Molecular Docking Study of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-21

Zhang

Chen

et al. 2021

Preprint

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PurposeJinwei decoction can enhance the anti-inflammatory effect of glucocorticoid (GC) on chronic obstructive pulmonary disease (COPD) by restoring the activity of HDAC2. But the upstream mechanism of Jinwei decoction on HDAC2 expression is not clear. ObjectiveTo explore whether Jinwei decoction can enhance the anti-inflammatory effect of GC on COPD through microRNA21 (miR-21) by network pharmacology. MethodsThe TCMSP database was used to screen active ingredients and target genes of Jinwei decoction, and miRWalk2.0 was used to predict downstream target genes of miR-21. COPD-related genes were identified by searching GeneCards and OMIM databases; Venny 2.1 was used to screen intersection genes; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of intersection genes were analyzed by R software. Protein-protein interactions (PPIs) were analyzed by Cytoscape 3.7.2 software to identify core genes. Finally, interactions between main compounds and potential targets were verified by molecular docking. ResultsTwo hundred ninety-two active ingredients, 316 Jinwei drug targets, 10170 miR-21 target genes, 6617 COPD target genes, and 184 intersection gene were identified. Eleven core proteins of PPI networks may be involved. GO enrichment analysis showed that oxidative stress, regulation of inflammatory response, hormone transport, and histone modification were involved; KEGG pathway enrichment analysis concentrated in the PI3K-Akt, mitogen-activated protein kinase (MAPK), HIF-1, neutrophil extracellular bactericidal network, and other signaling pathways. ConclusionJinwei decoction can regulate histone deacetylase-2 activity and enhance the anti-inflammatory effect of GC on COPD by modulating miR-21. Its mechanism of action may be related to its effect on the PI3K Akt, MAPK, and TNF signaling pathways and neutrophil extracellular trap formation through miR-21.

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Section: Discussionmentioning

confidence: 96%

WITHDRAWN: Network Pharmacology and Molecular Docking Study of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-21

Zhang

Chen

et al. 2021

Preprint

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“…Li et al reported that β-sitosterol is a candidate for the development of anti-virulence agents against pathogens that rely on cholesterol-dependent toxins for successful infections [25]. Zhou et al reported that β-sitosterol blocks the immune response mediated by RIG-I signaling and deleterious IFN production, providing a potential benefit for the treatment of influenza [26]. Parvez et.…”

Section: β-Sitosterol As Immunostimulant As Antiviral and As Antioxidantmentioning

confidence: 99%

Beta-Sitosterol: As Immunostimulant, Antioxidant and Inhibitor of SARS-CoV-2 Spike Glycoprotein

2020

Arch Pharmacol Ther

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Potential Inhibitor of SARS-CoV-2 M pro (COVID-19)", we have investigated the role of β-sitosterol as immunostimulant, antioxidant and inhibitory potential against Receptor Binding Domain (RBD) of SARS-CoV-2 Spike Glycoprotein with the aid of molecular docking. There are many studies which reveals the antioxidant and immune boosting role of β-sitosterol especially in viral infection including pneumoniae. This commentary emphasis on further potential of β-sitosterol in treatment of COVID-19 through molecular docking studies. We have targeted RBD of spike glycoprotein and performed molecular docking studies of β-sitosterol to find out its inhibitory potential of SARS-CoV-2. β-sitosterol have showed binding affinity -7.8 kcal/mol with 0 RMSD lower and upper bound. It formed one hydrogen bond with Ala-B:419 with bond length of 2.16A 0 . β-sitosterol has formed five alkyl bonds with Pro-C:384 (5.0A 0 , 4.66A 0 , 5.23A 0 , 4.27A 0 ) and with Lys-C:378 (4.66A 0 ). From present commentary, we have concluded that β-sitosterol can be used to enhance immunity against the SARS-CoV-2 infection as well as to restrict the viral invasion into the host cell through angiotensin converting enzyme-2 (ACE-2) by inhibiting spike glycoprotein. If we can increase the dietary intake of β-sitosterol and other phytosterols it can modulate the immunity which is todays need to face COVID-19.

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“…Nonetheless, the decrease in markers of inflammation might be a side effect of the cholesterol reduction. The influence of -sitosterol (Figure 3), the most abundant form in human serum (about 6 m), on inflammation caused by influenza A virus (IAV) infection was recently reported by Zhou et al [73].…”

Section: Cholesterol Reduction By Statins As Antiviral Treatmentmentioning

confidence: 70%

Cholesterol in virus entry into host cell: diet, phytosterols and statins

Montero

2021

FFHD

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Cholesterol has been reported in a number of studies to play an essential role in the effectiveness of viral infection in mammal cells. The main characteristic of cholesterol that is involved in viral infection is its capability to afford negative curvature to the membrane. This faculty of cholesterol has to do with the necessary steep curvature that the host cell membrane undergoes in the primary processes of viral infection, namely virus entry mechanism and building up of the virus reproduction scaffold, in particular for RNA enveloped viruses. Low cholesterol diet has been shown to reduce or even suppress virus infection efficiency in murine models or cell cultures; but to what extent a diet-based lowering of the blood cholesterol level may help preventing virus infection lacks still of enough scientific evidence. The use of statins in individuals with hypercholesterolemia has been recommended in the recent COVID-19 outbreak. The possibility of using sterols from natural sources in the diet or in supplementary concentrates has been suggested to be an alternative to drop the circulating cholesterol. In this manuscript, the most relevant and recent bibliography on the aforementioned issues is reviewed.

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β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling

Cited by 47 publications

References 88 publications

WITHDRAWN: Network Pharmacology and Molecular Docking Study of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-21

WITHDRAWN: Network Pharmacology and Molecular Docking Study of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-21

Beta-Sitosterol: As Immunostimulant, Antioxidant and Inhibitor of SARS-CoV-2 Spike Glycoprotein

Cholesterol in virus entry into host cell: diet, phytosterols and statins

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