Diosmin downregulates the expression of T cell receptors, pro-inflammatory cytokines and NF-κB activation against LPS-induced acute lung injury in mice

Imam, Faisal; Al-Harbi, Naif O.; Alharbi, Mohammed; Ansari, Mushtaq Ahmad; Zoheir, Khairy M.A.; Iqbal, Muzaffar; Anwer, Md. Khalid; Hoshani, Ali R. Al; Attia, Sabry M.; Ahmad, Sheikh F.

doi:10.1016/j.phrs.2015.09.001

Cited by 82 publications

(49 citation statements)

References 58 publications

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“…1708882, Bio-Rad). According to previous reports6566, the levels of mRNA, expressed as relative mRNA levels compared with control, were calculated three times in duplicate after normalization to β-actin. Sequences for primers were design by Oligo 7 software (Table S3).…”

Section: Methodsmentioning

confidence: 99%

Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4/NF-κBp65/MAPKs signaling cascade

Wang

et al. 2017

Sci Rep

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Resveratrol (RSV) is a natural compound exhibiting anti-inflammatory effect, but the anti-inflammatory mechanism has not been fully understood. This study is aimed to evaluate the anti-inflammatory activity and mechanism of RSV in lipopolysaccharides-induced rats’ model. The visceral wet/dry weight ratios and the changes of hematologic and biochemical indices indicated that LPS- stimulation mainly caused damages to liver and lung, while pretreatment with RSV could alleviate the lesions. The cytokine assays showed that RSV could markedly decrease the production of proinflammatory mediators and cytokines (IL-1, IL-1β, IL-6, NO, iNOS and COX-2), and increase the expression of anti-inflammatory mediator (IL-10). RSV could inhibit TLR4 signaling pathway by down-regulating the mRNA levels of MyD88 and TRAF6, and suppressing the TLR4 protein. RSV could inhibit the signaling cascades of NF-κBp65 and MAPKs through down-regulating the mRNA levels of IκBα, p38MAPK, JNK, ERK1, ERK2 and ERK5 in liver and lung, and suppressing the dynamic changes of proteins and phosphorylated proteins including IκBα, NF-κBp65, p38MAPK, JNK, ERK1/2 and ERK5 from tissue’s cytoplasm to nucleus. In conclusion, RSV possessed a therapeutic effect on LPS-induced inflammation in rats and the mechanism mainly attributed to suppressing the signaling cascades of NF-κBp65 and MAPKs by inhibiting the TLR4 signaling pathway.

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Section: Methodsmentioning

confidence: 99%

Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4/NF-κBp65/MAPKs signaling cascade

Wang

et al. 2017

Sci Rep

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“…Most of the bioactivities of diosmin are based on strong antioxidant effects on levels of free radical scavenger activity to reduce oxidative stress. Strong anti-inflammatory effects of diosmin (or diosmetin) were demonstrated by suppression of proinflammatory cytokines and mediators (e.g., TNF-α, IL-1β, IL-6, IL-17, iNOS and COX-2) (Imam et al, 2015;Shalkami et al, 2018;Yu et al, 2014). The suppression of the inflammatory cascade by diosmin is based, at least in part, via inhibition of NFκB signaling (Shalkami et al, 2018;Yu et al, 2014).…”

Section: Diosmin and Diosmetinmentioning

confidence: 99%

“…The suppression of the inflammatory cascade by diosmin is based, at least in part, via inhibition of NFκB signaling (Shalkami et al, 2018;Yu et al, 2014). It was demonstrated that diosmin attenuated the canonical NFκB pathway on levels of IκB kinase (IKK) to decrease IκB-α phosphorylation (Imam et al, 2015). Another pathway affected by diosmin to alleviate oxidative stress and inflammation may include stimulation of the PPAR-γ pathway as demonstrated in a radiationinduced hepatic fibrosis rat model (Hasan et al, 2017).…”

Section: Diosmin and Diosmetinmentioning

confidence: 99%

The role of rutin and diosmin, two citrus polyhydroxyflavones in disease prevention and treatment

Gosslau¹,

Ho²,

Li³

2019

JFB

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Chronic inflammation and dysregulation of apoptotic pathways leading to free radical-induced tissue damage are widely recognized as major underlying causes of major degenerative diseases, including cancer, diabetes, neurological and cardiovascular disorders. Citrus fruits are rich sources of polyphenolic flavonoids well known for their wide range of pharmacological properties. Rutin (quercetin-3-O-rutinoside) and diosmin (diosmetin 7-Orutinoside) are two major polyhydroxyflavone glycosides abundantly found in citrus peels and, to a lesser extent, in pulp of a variety of different citrus species. During digestion, hydrolysis by intestinal enzymes and gut microbiota lead to the release of their corresponding bioactive aglycones (e.g., quercetin or diosmetin). Data obtained in cell-based, animal and clinical studies demonstrated strong preventive and/or therapeutic effects of rutin and its aglycone flavone quercetin. Although lesser studies available, our recent literature review suggests diosmin as promising citrus fruit polyhydroxyflavonoids, effective against various diseases associated with chronic inflammation.

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“…Diosmin highlighted the third strongest binding energy at the active site of the MPro with a MoLDock score of −174.1260 and a HBond of −27.2572. As signaled for the rutin, in preclinical models the diosmin reduced the level of interleukin 6 as well as the number of CD4 and CD8 receptors in T cells [4]. Recently, Caly and colleagues reported a potential antiretroviral activity of the anti-parasitic agent ivermectin against SARS-CoV-2 virus.…”

mentioning

confidence: 94%

Potential Unconventional Medicines for the Treatment of SARS-CoV-2

Coppola

Mondola²

2020

Drug Res (Stuttg)

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Diosmin downregulates the expression of T cell receptors, pro-inflammatory cytokines and NF-κB activation against LPS-induced acute lung injury in mice

Cited by 82 publications

References 58 publications

Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4/NF-κBp65/MAPKs signaling cascade

Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4/NF-κBp65/MAPKs signaling cascade

The role of rutin and diosmin, two citrus polyhydroxyflavones in disease prevention and treatment

Potential Unconventional Medicines for the Treatment of SARS-CoV-2

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