Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in interleukin-1β-treated hepatocytes

Yoshigai, Emi; Machida, Toru; Okuyama, Tetsuya; Mori, Masatoshi; Murase, Hiromitsu; Yamanishi, Ryota; Okumura, Tadayoshi; Ikeya, Yukinobu; Nishino, Hoyoku; Nishizawa, Mikio

doi:10.1016/j.bbrc.2013.08.029

Cited by 55 publications

(38 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, theaflavins, which are produced in black tea through the oxidative polymerization of two flavanol molecules, suppress iNOS induction by preventing NF-κB activation in macrophages [45]. Third, nobiletin, which is a polymethoxylated flavone found in citrus fruits, also suppresses iNOS expression and decreases the nuclear NF-κB levels in hepatocytes [24]. All of these data support the idea that flavanols in FRLFE may inhibit NF-κB activation by affecting the IκB-α phosphorylation and the NF-κB translocation into the nucleus.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the suppression of IL-1β-induced iNOS expression generally correlates with anti-inflammatory activity of the compound. We demonstrated that NO is a sensitive marker of liver protection that can be used to monitor inflammatory responses to functional foods, such as the active hexose correlated compound [20], [21] and Japanese herbal medicines and their constituents [19], [22]–[24]. These compounds suppress iNOS induction at the transcriptional level through transcription factors, including nuclear factor κB (NF-κB) [25].…”

Section: Introductionmentioning

confidence: 99%

“…asRNA-mediated posttranscriptional regulation is thought to be a general mechanism to modulate the stability of mRNAs involved in inflammation [27], [29]. Furthermore, several herbal constituents have been shown to suppress the expression of iNOS asRNA [19], [22]–[24]. Therefore, FRLFE is expected to be involved in the asRNA-mediated regulation of iNOS gene expression.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Anti-Inflammatory Effects of Flavanol-Rich Lychee Fruit Extract in Rat Hepatocytes

et al. 2014

Self Cite

View full text Add to dashboard Cite

Flavanol (flavan-3-ol)-rich lychee fruit extract (FRLFE) is a mixture of oligomerized polyphenols primarily derived from lychee fruit and is rich in flavanol monomers, dimers, and trimers. Supplementation with this functional food has been shown to suppress inflammation and tissue damage caused by high-intensity exercise training. However, it is unclear whether FRLFE has in vitro anti-inflammatory effects, such as suppressing the production of the proinflammatory cytokine tumor necrosis factor α (TNF-α) and the proinflammatory mediator nitric oxide (NO), which is synthesized by inducible nitric oxide synthase (iNOS). Here, we analyzed the effects of FRLFE and its constituents on the expression of inflammatory genes in interleukin 1β (IL-1β)-treated rat hepatocytes. FRLFE decreased the mRNA and protein expression of the iNOS gene, leading to the suppression of IL-1β-induced NO production. FRLFE also decreased the levels of the iNOS antisense transcript, which stabilizes iNOS mRNA. By contrast, unprocessed lychee fruit extract, which is rich in flavanol polymers, and flavanol monomers had little effect on NO production. When a construct harboring the iNOS promoter fused to the firefly luciferase gene was used, FRLFE decreased the luciferase activity in the presence of IL-1β, suggesting that FRLFE suppresses the promoter activity of the iNOS gene at the transcriptional level. Electrophoretic mobility shift assays indicated that FRLFE reduced the nuclear transport of a key regulator, nuclear factor κB (NF-κB). Furthermore, FRLFE inhibited the phosphorylation of NF-κB inhibitor α (IκB-α). FRLFE also reduced the mRNA levels of NF-κB target genes encoding cytokines and chemokines, such as TNF-α. Therefore, FRLFE inhibited NF-κB activation and nuclear translocation to suppress the expression of these inflammatory genes. Our results suggest that flavanols may be responsible for the anti-inflammatory and hepatoprotective effects of FRLFE and may be used to treat inflammatory diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Anti-Inflammatory Effects of Flavanol-Rich Lychee Fruit Extract in Rat Hepatocytes

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, in the rice plant, NATs regulate expression of a protein important for phosphate homeostasis (Jabnoune et al, 2013). Similarly NAT of interleukin (IL) 1 beta) (Lu et al, 2013), iNOS (inducible nitric oxide synthase) (Yoshigai et al, 2013), and ubiquitin c-terminal hydrolase (uch) (Carrieri et al, 2012), Huntington's disease (Chung et al, 2011) suppress expression of their complementary transcripts. Importantly, inhibition of expression of NATs has resulted in upregulation of gene specific transcription (Modarresi et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Asymmetric localization of natural antisense RNA of neuropeptide sensorin in Aplysia sensory neurons during aging and activity

et al. 2014

View full text Add to dashboard Cite

Despite the advances in our understanding of transcriptome, regulation and function of its non-coding components continue to be poorly understood. Here we searched for natural antisense transcript for sensorin (NAT-SRN), a neuropeptide expressed in the presynaptic sensory neurons of gill-withdrawal reflex of the marine snail Aplysia californica. Sensorin (SRN) has a key role in learning and long-term memory storage in Aplysia. We have now identified NAT-SRN in the central nervous system (CNS) and have confirmed its expression by northern blotting and fluorescent RNA in situ hybridization. Quantitative analysis of NAT-SRN in micro-dissected cell bodies and processes of sensory neurons suggest that NAT-SRN is present in the distal neuronal processes along with sense transcripts. Importantly, aging is associated with reduction in levels of NAT-SRN in sensory neuron processes. Furthermore, we find that forskolin, an activator of CREB signaling, differentially alters the distribution of SRN and NAT-SRN. These studies reveal novel insights into physiological regulation of natural antisense RNAs.

show abstract

“…For example, Citrus polyphenol limonene promoted NO• production in several studies, leading to an inhibition in proliferation of human melanoma A375 cells [22], leukemia HL-60 cells [23], and epidermoid carcinoma A431 cells [24]. On the other hand, Sudachitin, a polymethoxyflavone from Citrus sudachi, inhibited LPS-mediated NO• production and iNOS protein expression in RAW264.7 macrophages [9], and Citrus nobiletin reduced NO• levels and decreased iNOS expression in hepatocytes [25]. Our data indicate a direct relationship between increased NO• production and loss of cell viability (Figs.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic properties of Citrus sudachi Hort, ex Shirai (Rutaceae) extract on human A549 and HepG2 cancer cells

Kim¹,

Kim²

2016

Trop. J. Pharm Res

View full text Add to dashboard Cite

Purpose: To investigate whether Citrus sudachi harvested at two stages of maturity can induce toxicity in a cell-specific manner and to determine the possible mechanisms of Citrus sudachi-induced cytotoxic responses in two types of cancer cells (human lung adenocarcinoma A549 and hepatocellular carcinoma HepG2 cells) and two normal cell lines (lung 16HBE140-and liver CHANG cells). Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodidle assay were used to test the antiproliferative activity and apoptosis of methanol extract of Citrus sudachi, respectively. Griess reaction and reverse transcriptase-polymerase chain reaction (RT-PCR) were carried out to evaluate nitric oxide (NO • ) production and the mRNA levels of inhibitors of apoptosis (IAP). Results: Citrus sudachi exerted cytotoxicity in a time-dependent manner in cancer cells which increased with increase in maturity but did not affect normal cells. Citrus sudachi was found to induce accumulation of cells in the sub

show abstract

Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in interleukin-1β-treated hepatocytes

Cited by 55 publications

References 23 publications

The Anti-Inflammatory Effects of Flavanol-Rich Lychee Fruit Extract in Rat Hepatocytes

The Anti-Inflammatory Effects of Flavanol-Rich Lychee Fruit Extract in Rat Hepatocytes

Asymmetric localization of natural antisense RNA of neuropeptide sensorin in Aplysia sensory neurons during aging and activity

Apoptotic properties of Citrus sudachi Hort, ex Shirai (Rutaceae) extract on human A549 and HepG2 cancer cells

Contact Info

Product

Resources

About