Prunetin

Tuberc Respir Dis (Seoul). 2013 Nov;75(5):205-9.

Effect of Prunetin on TNF-α-Induced MUC5AC Mucin Gene Expression, Production, Degradation of IκB and Translocation of NF-κB p65 in Human Airway Epithelial Cells.[Pubmed: 24348668]

We investigated whether Prunetin significantly affects tumor necrosis factor-α (TNF-α)-induced MUC5AC mucin gene expression, production, inhibitory kappa B (IκB) degradation and nuclear factor kappa B (NF-κB) p65 translocation in human airway epithelial cells.
METHODS AND RESULTS:
Confluent NCI-H292 cells were pretreated with Prunetin for 30 minutes and then stimulated with TNF-α for 24 hours or the indicated periods. MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The effect of Prunetin on TNF-α-induced degradation of IκB and translocation of NF-κB p65 was investigated by western blot analysis. We found that incubation of NCI-H292 cells with Prunetin significantly inhibited mucin production and down-regulated the MUC5AC gene expression induced by TNF-α. Prunetin inhibited TNF-α-induced degradation of IκB and translocation of NF-κB p65.
CONCLUSIONS:
This result suggests that Prunetin inhibits the NF-κB signaling pathway, which may explain its role in the inhibition of MUC5AC mucin gene expression and production regulated by the NF-κB signaling pathway.

Free Radic Biol Med. 2014 May;70:255-64.

Biochanin A and prunetin improve epithelial barrier function in intestinal CaCo-2 cells via downregulation of ERK, NF-κB, and tyrosine phosphorylation.[Pubmed: 24631489]

The single-layered gut epithelium represents the primary line of defense against environmental stressors; thereby monolayer integrity and tightness are essentially required to maintain gut health and function. To date only a few plant-derived phytochemicals have been described as affecting intestinal barrier function.
CONCLUSIONS:
We investigated the impact of 28 secondary plant compounds on the barrier function of intestinal epithelial CaCo-2/TC-7 cells via transepithelial electrical resistance (TEER) measurements. Apart from genistein, the compounds that had the biggest effect in the TEER measurements were biochanin A and Prunetin. These isoflavones improved barrier tightness by 36 and 60%, respectively, compared to the untreated control. Furthermore, both isoflavones significantly attenuated TNFα-dependent barrier disruption, thereby maintaining a high barrier resistance comparable to nonstressed cells. In docking analyses exploring the putative interaction with the tyrosine kinase EGFR, these novel modulators of barrier tightness showed very similar values compared to the known tyrosine kinase inhibitor genistein.
CONCLUSIONS:
Both biochanin A and Prunetin were also identified as potent reducers of NF-κB and ERK activation, zonula occludens 1 tyrosine phosphorylation, and metalloproteinase-mediated shedding activity, which may account for the barrier-improving ability of these isoflavones.

Biomed Pharmacother . 2018 Oct;106:1469-1477.

Prunetin inhibits lipopolysaccharide-induced inflammatory cytokine production and MUC5AC expression by inactivating the TLR4/MyD88 pathway in human nasal epithelial cells[Pubmed: 30119221]

Abstract Allergic rhinitis (AR) is a chronic upper respiratory disorder characterized by inflammation of the nasal mucosa. Prunetin is an O-methylated isoflavone, which has been found to possess anti-inflammatory activity. The aim of the current study was to evaluate the effect of Prunetin on inflammatory cytokine and mucus production and its underlying mechanism in nasal epithelial cells. Results showed that treatment with Prunetin (10, 30, and 50 μM) inhibited lipopolysaccharide (LPS)-induced expression and secretion of interleukin (IL)-6, IL-8, and mucin 5 AC (MUC5 AC) in RPMI2650 cells, and attenuated the effect of LPS on toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) expression. TAK-242 (an inhibitor of TLR4) treatment or TLR4 knockdown attenuated LPS-induced expression and secretion of IL-6, IL-8 and MUC5 AC. In conclusion, Prunetin inhibited LPS-induced inflammatory cytokine production and MUC5 AC expression and secretion by inactivating the TLR4/MyD88 pathway in human nasal epithelial cells. These results suggested that Prunetin might be a useful agent in the treatment of AR. Keywords: Allergic rhinitis; Inflammatory cytokine; MUC5AC; Prunetin; TLR4/MyD88 pathway.

Food Chem Toxicol. 2013 Aug;58:124-32.

Anti-inflammatory effect of prunetin via the suppression of NF-κB pathway.[Pubmed: 23597450]

Prunetin is an O-methylated isoflavone, which is found in Prunus yedoensis. To date no report has been published on anti-inflammatory activities of Prunetin.
METHODS AND RESULTS:
In the present study, the anti-inflammatory effect of Prunetin on LPS-stimulated RAW 264.7 macrophage and LPS-induced septic shock model were investigated. Inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) expressions were determined by western blot and or realtime-PCR (RT-PCR). To elucidate its underlying mechanism, nuclear factor-kappa B (NF-κb) activation and its downstream pathways were investigated by NF-κB transcription factor assay, reporter gene expression, and western blot. In vivo anti-inflammatory effects of Prunetin were evaluated in LPS-induced endotoxemia. Promoter assay revealed that Prunetin inhibits LPS-induced nitric oxide and prostaglandin E2 production through the suppression of iNOS and COX-2 at the transcriptional level. In addition, Prunetin inhibits NF-κB-dependent inflammatory responses by modulating IκB kinase (IKK)-inhibitor κBα (IκBα)-NF-κB signaling. Consistent with these results, Prunetin significantly reduced serum levels of inflammatory cytokines and mortality in mice challenged with lipopolysaccharide.
CONCLUSIONS:
These findings offer a potential mechanism for the anti-inflammatory activity of Prunetin.

Phytother Res. 2011 Aug;25(8):1196-200.

Inhibition of secretion, production and gene expression of mucin from cultured airway epithelial cells by prunetin.[Pubmed: 21305630]

This study investigated whether Prunetin significantly affects the secretion, production and gene expression of mucin from cultured airway epithelial cells.
METHODS AND RESULTS:
Confluent primary rat tracheal surface epithelial (RTSE) cells were pretreated with adenosine triphosphate (ATP) for 5 min and then chased for 30 min in the presence of Prunetin to assess the effect on mucin secretion using enzyme-linked immunosorbent assay (ELISA). At the same time, confluent NCI-H292 cells were pretreated with Prunetin for 30 min and then stimulated with epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA) for 24 h, respectively. The MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription-polymerase chain reaction (RT-PCR) and ELISA. The results were as follows: (1) Prunetin significantly suppressed ATP-induced mucin secretion from cultured RTSE cells; (2) Prunetin inhibited the production of MUC5AC mucin protein induced by EGF or PMA from NCI-H292 cells; (3) Prunetin also inhibited the expression of MUC5AC mucin gene induced by EGF or PMA from NCI-H292 cells.
CONCLUSIONS:
This result suggests that Prunetin can regulate the secretion, production and gene expression of mucin, by directly acting on airway epithelial cells.

Biochem Pharmacol. 2013 May 15;85(10):1525-33.

Molecular mechanisms underlying the anti-obesity potential of prunetin, an O-methylated isoflavone.[Pubmed: 23438470]

Prunetin is an O-methylated isoflavone, which is a type of flavonoid. There are a limited number of reports detailing the biological activities of Prunetin. Although an anti-inflammatory effect of Prunetin has been reported in vitro, to our knowledge, there have been no reports on anti-adipogenic effects of Prunetin in obese animals.
METHODS AND RESULTS:
The aims of this study were to determine whether Prunetin suppresses high-fat diet (HFD)-induced adipogenesis in the liver and visceral adipose tissues of mice, and to explore the underlying mechanisms mediating the actions of Prunetin. To this end, mice were fed a HFD for 10 weeks to induce obesity, and Prunetin (10 μg/kg or 20 μg/kg) was administered in the last 3 weeks. Compared to saline-treated mice, mice treated with Prunetin showed significantly reduced body weight gain, visceral fat pad weights, and plasma glucose levels. We found that Prunetin significantly inhibited the HFD-induced upregulation of the expression of important adipogenic genes (PPARγ, C/EBPα, SREBP, aP2, LPL adiponectin, and leptin), and suppressed HFD-mediated increase in expression of lipid metabolism-related genes (SREBP, PPARγ, LXR, and HMG-CoA) in the liver tissues. Furthermore, Prunetin induced expression of adiponectin receptors 1 and 2 (adipoR1, adipoR2), as well as that of AMP-activated protein kinase (AMPK) in the liver and adipose tissue.
CONCLUSIONS:
These results suggest that Prunetin mediates anti-obesity/adipogenesis effects by suppressing obesity-related transcription through a feedback mechanism that regulates the expression of adiponectin, adipoR1, adipoR2, and AMPK.