Dietary apigenin reduces LPS‐induced expression of miR‐155 restoring immune balance during inflammation

Arango, Daniel; Diosa-Toro, Mayra; Rojas-Hernandez, Laura S.; Cooperstone, Jessica L.; Schwartz, Steven J.; Mo, Xiaokui; Jiang, Jinmai; Schmittgen, Thomas D.; Doseff, Andrea I.

doi:10.1002/mnfr.201400705

Cited by 76 publications

(57 citation statements)

References 51 publications

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“…Predominantly, these miRNA species are linked to some, if not all, pathways in innate immunity in cellular [146, 147] and in animal models [148, 149]. One of the well-known anti-inflammatory dietary components is flavonoids.…”

Section: Discussionmentioning

confidence: 99%

“…One of the well-known anti-inflammatory dietary components is flavonoids. In vitro investigation of a flavonoid, apigenin, revealed that it suppresses LPS-induced miR-155 expression in macrophages, leading to upregulation of the anti-inflammatory regulators forkhead box O3a and MAD-related protein 2 [146]. The protective effect was further elaborated by a murine sepsis model in which an apigenin-rich diet considerably reduced the expression of miR-155 and TNF-α in the lungs [146].…”

Section: Discussionmentioning

confidence: 99%

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The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Chan

Wong

et al. 2016

Crit Care

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BackgroundSepsis coincides with altered gene expression in different tissues. Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and circular RNAs are important molecules involved in the crosstalk with various pathways pertinent to innate immunity, mitochondrial functions, and apoptosis.MethodsWe searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/Abstract words (“microRNA”, “long non-coding RNA”, “circular RNA”, “sepsis” and/or “septic shock”) from inception to Sep 2016. Studies investigating the role of host-derived microRNA, long non-coding RNA, and circular RNA in the pathogenesis of and as biomarkers or therapeutics in sepsis were included. Data were extracted in terms of the role of non-coding RNAs in pathogenesis, and their applicability for use as biomarkers or therapeutics in sepsis. Two independent researchers assessed the quality of studies using a modified guideline from the Systematic Review Center for Laboratory animal Experimentation (SYRCLE), a tool based on the Cochrane Collaboration Risk of Bias tool.ResultsObservational studies revealed dysregulation of non-coding RNAs in septic patients. Experimental studies confirmed their crosstalk with JNK/NF-κB and other cellular pathways pertinent to innate immunity, mitochondrial function, and apoptosis. Of the included studies, the SYRCLE scores ranged from 3 to 7 (average score of 4.55). This suggests a moderate risk of bias. Of the 10 articles investigating non-coding RNAs as biomarkers, none of them included a validation cohort. Selective reporting of sensitivity, specificity, and receiver operating curve was common.ConclusionsAlthough non-coding RNAs appear to be good candidates as biomarkers and therapeutics for sepsis, their differential expression across tissues complicated the process. Further investigation on organ-specific delivery of these regulatory molecules may be useful.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1555-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Chan

Wong

et al. 2016

Crit Care

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“…9). Indeed, it was recently reported that the mechanism by which the flavone apigenin exerts its antiinflammatory activity in macrophages is through the down-regulation of microRNA-155 induced by infection (Arango et al, 2015). Interestingly, AtDMR6 is induced by salicylic acid and AtDMR6 is expressed around the infection site during pathogen attack, so a complex feedback inhibition regulation by flavones may exist to balance levels of salicylic acid.…”

Section: Discussionmentioning

confidence: 99%

The Identification of Maize and Arabidopsis Type I FLAVONE SYNTHASEs Links Flavones with Hormones and Biotic Interactions

et al. 2015

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Flavones are a major group of flavonoids with diverse functions and are extensively distributed in land plants. There are two different classes of FLAVONE SYNTHASE (FNS) enzymes that catalyze the conversion of the flavanones into flavones. The FNSI class comprises soluble Fe 2+ /2-oxoglutarate-dependent dioxygenases, and FNSII enzymes are oxygen-and NADPH-dependent cytochrome P450 membrane-bound monooxygenases. Here, we describe the identification and characterization of FNSI enzymes from maize (Zea mays) and Arabidopsis (Arabidopsis thaliana). In maize, ZmFNSI-1 is expressed at significantly higher levels in silks and pericarps expressing the 3-deoxy flavonoid R2R3-MYB regulator P1, suggesting that ZmFNSI-1 could be the main enzyme for the synthesis of flavone O-glycosides. We also show here that DOWNY MILDEW RESISTANT6 (AtDMR6), the Arabidopsis homologous enzyme to ZmFNSI-1, has FNSI activity. While dmr6 mutants show loss of susceptibility to Pseudomonas syringae, transgenic dmr6 plants expressing ZmFNSI-1 show similar susceptibility to wild-type plants, demonstrating that ZmFNSI-1 can complement the mutant phenotype. AtDMR6 expression analysis showed a tissue-and developmental stage-dependent pattern, with high expression in cauline and senescing leaves. Finally, we show that Arabidopsis cauline and senescing leaves accumulate apigenin, demonstrating that Arabidopsis plants have an FNSI activity involved in the biosynthesis of flavones. The results presented here also suggest cross talk between the flavone and salicylic acid pathways in Arabidopsis; in this way, pathogens would induce flavones to decrease salicylic acid and, hence, increase susceptibility.

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“…Very recently, a number of studies have focused on the activity of apigenin. These studies reported different activities for the flavonoid: antileukemic activities [74], increased chemosensitivity of cancer cells to drugs [75], anti-inflammatory activities [76], inhibition of nitric oxide production [77], and immune balance during inflammation [78]. In addition, apigenin was presented as a promising molecule for cancer prevention [79].…”

Section: Discussionmentioning

confidence: 99%

Potential Antitumor Activity and Apoptosis Induction of Glossostemon bruguieri Root Extract against Hepatocellular Carcinoma Cells

Alwahibi

Khalil

Ibrahim

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Glossostemon bruguieri (moghat) is used as a nutritive and demulcent drink. This study was performed to investigate the antiproliferative effects of moghat root extract (MRE) and its apoptotic mechanism in hepatocellular carcinoma (HCC) cells, HepG2 and Hep3B. MTT assay, morphological changes, apoptosis enzyme linked immunosorbent assay, caspase and apoptotic activation, flow cytometry, and immunoblot analysis were employed. The IC50 of MRE for HepG2 (910 ± 6 μg/ml) and for Hep3B (1510 ± 5 μg/ml) induced significant growth-inhibitory effects against HCC cells, with no cytotoxic effect on normal hepatocytes. MRE treatment induced apoptotic effects to HepG2 cells in a caspase-dependent manner and via upregulating p53/p21 and PCNA. The upregulation of p21 was controlled by p53 expression in HepG2 but not in Hep3B despite upregulation of Bax protein in both cell lines. Interestingly, p21 may be a remarkable switch to G1 arrest in HepG2 cells, but not in Hep3B cells. In addition, Fas- and mitochondria-mediated pathways were found to be involved in MRE-induced apoptosis in Hep3B cells. The GC-MS analysis of MRE revealed two major constituents of pharmaceutical importance: the flavonoid apigenin (17.04%) and the terpenoid squalene (11.32%). The data presented in this paper introduces G. bruguieri as a promising nontoxic herb with therapeutic potential for HCC. To the authors' knowledge, the present study provides the first report on the anticancer activity of MRE on HCC cells.

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Dietary apigenin reduces LPS‐induced expression of miR‐155 restoring immune balance during inflammation

Abstract: These results demonstrate that apigenin and apigenin-rich diets exert effective anti-inflammatory activity in vivo by reducing LPS-induced expression of miR-155, thereby restoring immune balance.

Cited by 76 publications

References 51 publications

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

The Identification of Maize and Arabidopsis Type I FLAVONE SYNTHASEs Links Flavones with Hormones and Biotic Interactions

Potential Antitumor Activity and Apoptosis Induction of Glossostemon bruguieri Root Extract against Hepatocellular Carcinoma Cells

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