Molecular chemoprevention by morin – A plant flavonoid that targets nuclear factor kappa B in experimental colon cancer

Sharma, Sharada H.; Kumar, Jayasurya Suresh; Chellappan, David Raj; Sangeetha, N.

doi:10.1016/j.biopha.2018.02.035

Cited by 58 publications

(40 citation statements)

References 35 publications

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“…In this in vitro study, we also demonstrated that MH prevents the release of proinflammatory cytokines in LPS-stimulated macrophages by inhibiting TREM-1/TLR4/NF-κB signaling pathway ( Figure 6 ). Similarly, it has been shown that MH suppresses the activation of NF-κB and downstream proinflammatory mediators in various experimental models (Wang et al, 2013; Tian et al, 2017; Sharma et al, 2018).…”

Section: Discussionmentioning

confidence: 86%

Morin Hydrate Inhibits TREM-1/TLR4-Mediated Inflammatory Response in Macrophages and Protects Against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Yao

Huang

et al. 2019

Front. Pharmacol.

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This study aims to investigate the protective effects of morin hydrate (MH) against acute liver injury induced by carbon tetrachloride (CCl4) in mice and to elucidate the possible molecular mechanism of action. Mice were pretreated with MH (50 mg/kg body weight) or vehicle by oral gavage once daily for 5 days, followed by intraperitoneal injection of a single dose of CCl4 (1 ml/kg in olive oil). Mice were sacrificed 24 h later; the blood and liver samples were harvested for analysis. We also used the model of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in vitro and examined the effects of MH and its mechanism of action on the inflammatory response. Our results revealed that MH remarkably attenuated liver histopathological alterations, serum transaminases, hepatocytes death, and inflammatory response induced by CCl4. Importantly, MH reduced expression of the triggering receptor expressed on myeloid cells-1 (TREM-1) and toll-like receptor 4 (TLR4) both in vivo and in vitro experiments. This inhibitory effect MH on expression of the TREM-1 and TLR4 in cell culture was further heightened after TREM-1 knockdown with small interfering RNA (siRNA). Moreover, MH dramatically suppressed the inhibitor of kappa B α (IκBα) degradation and subsequent nuclear factor-kappa B (NF-κB) p65 translocation into the nucleus and NF-κB-mediated cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6. Additionally, MH also ameliorated CCl4-induced oxidative stress by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in the injured livers. Taken together, MH has hepatoprotective activity, and this effect may be elicited by attenuating macrophage-mediated inflammatory responses via inhibition TREM-1/TLR4/NF-κB signaling and by regulating hepatic oxidative stress via enhancement Nrf2/HO-1 antioxidant pathway.

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Section: Discussionmentioning

confidence: 86%

Morin Hydrate Inhibits TREM-1/TLR4-Mediated Inflammatory Response in Macrophages and Protects Against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Yao

Huang

et al. 2019

Front. Pharmacol.

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“…Although the details of the anti-inflammatory mechanisms of morin hydrate are still not clear, it is reported to have anti-inflammatory effect in inflammatory bowel disease through the inhibition of nitric oxide synthase activity and in ameliorating Alzheimer's disease by reducing oxidative stress ( 36 37 ). In addition, morin hydrate inhibits TREM-1/TLR4-mediated inflammatory responses in the mouse model of carbon tetrachloride-induced liver injury ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…Besides, morin hydrate exerts its anti-inflammatory effects in atherosclerosis through autophagy regulation and reduces TNF-α expression mediated by cAMP-PKA-AMPK-SIR1 signaling pathway ( 12 ). Morin hydrate also regulates NF-κB pathway, leading to reduced production of pro-inflammatory cytokines, such as TNF-α, IL-6, cyclooxygenase-2, prostaglandin E2, in animal model of colon cancer ( 36 ), and inhibits IL-1β-induced inflammation in osteoarthritis model ( 37 ). In this study, we observed that mice treated with morin hydrate showed decreased levels of pro-inflammatory cytokines in lungs during influenza infection, which may be associated with its effects on immune cells, in addition to direct inhibition of influenza virus entry.…”

Section: Discussionmentioning

confidence: 99%

Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice

et al. 2020

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Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2′,4′-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-кB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/ PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

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“…Monte Carlo, simulated annealing, and evolutionary methods are examples of stochastic search method, and they are the most common in molecular docking softwares [32,33]. In the pathway that triggers the activation of nuclear factor κB (NF-κB) in tumor necrosis factor (TNF) stimulated cells ( Figure 6), IKK complex is a target for many flavonoids such as apinegin [34], luteolin [34], acacetin [35], ochnaflavone [35], delphinidin [35], and morin [36].…”

Section: Theory Of Molecular Dockingmentioning

confidence: 99%

“…In LPS-stimulated cells (Figure 7), epigallocatechin-3-gallate (EGCG) [37] and morin [36] inhibited the activation of NF-κB activity by IKK complex inhibition. Besides that, EGCG also inhibited p38 MAP kinase activity [37].…”

Section: Molecular Targets For Flavonoidsmentioning

confidence: 99%

Molecular Mechanism of Flavonoids Using Fluorescence Spectroscopy and Computational Tools

Povinelli¹,

Zazeri²,

Cornélio³

2020

Flavonoids - A Coloring Model for Cheering Up Life

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With more than 4000 compounds identified up to now, flavonoids are present in human diet since they can be found in fruits, vegetables, seeds, grains, and beverages, such as wine and tea. Over the years, medicinal properties of these polyphenolic compounds have been noticed. Consequently, the search for the biological targets and for the description of flavonoids action mechanism has been growing. Fluorescence spectroscopy and molecular docking are techniques based on physical theories which have been helping researchers to describe the interaction between flavonoids and biological targets. In this way, this chapter comes not only as an attempt to gather some works dedicated to explain flavonoid molecular mechanisms of action but also to introduce a brief theory of steady-state fluorescence spectroscopy and molecular docking.

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Molecular chemoprevention by morin – A plant flavonoid that targets nuclear factor kappa B in experimental colon cancer

Cited by 58 publications

References 35 publications

Morin Hydrate Inhibits TREM-1/TLR4-Mediated Inflammatory Response in Macrophages and Protects Against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Morin Hydrate Inhibits TREM-1/TLR4-Mediated Inflammatory Response in Macrophages and Protects Against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice

Molecular Mechanism of Flavonoids Using Fluorescence Spectroscopy and Computational Tools

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