Sakuranetin

Analysis on blast fungus-responsive characters of a flavonoid phytoalexin sakuranetin; accumulation in infected rice leaves, antifungal activity and detoxification by fungus.[Pubmed: 25093982]

Molecules. 2014 Aug 4;19(8):11404-18.

To understand the role of the rice flavonoid phytoalexin (PA) Sakuranetin for blast resistance, the fungus-responsive characteristics were studied.
METHODS AND RESULTS:
Young rice leaves in a resistant line exhibited hypersensitive reaction (HR) within 3 days post inoculation (dpi) of a spore suspension, and an increase in Sakuranetin was detected at 3 dpi, increasing to 4-fold at 4 dpi. In the susceptible line, increased Sakuranetin was detected at 4 dpi, but not at 3 dpi, by which a large fungus mass has accumulated without HR. Induced expression of a PA biosynthesis gene OsNOMT for naringenin 7-O-methyltransferase was found before accumulation of Sakuranetin in both cultivars. The antifungal activity of Sakuranetin was considerably higher than that of the major rice diterpenoid PA momilactone A in vitro and in vivo under similar experimental conditions. The decrease and detoxification of Sakuranetin were detected in both solid and liquid mycelium cultures, and they took place slower than those of momilactone A. Estimated local concentration of Sakuranetin at HR lesions was thought to be effective for fungus restriction, while that at enlarged lesions in susceptible rice was insufficient.
CONCLUSIONS:
These results indicate possible involvement of Sakuranetin in blast resistance and its specific relation to blast fungus.

Sakuranetin induces adipogenesis of 3T3-L1 cells through enhanced expression of PPARgamma2.[Pubmed: 18522800 ]

Biochem Biophys Res Commun. 2008 Aug 8;372(4):835-9.

Sakuranetin (5,4'-dihydroxy-7-methoxyflavone) belongs to the flavanone class of polyphenols predominantly known as phytoalexin in rice plant.
METHODS AND RESULTS:
In this study, we demonstrate that Sakuranetin strongly induces differentiation of 3T3-L1 preadipocytes, as evidenced by increased triglyceride accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity. In addition, even in the absence of adipogenic hormonal stimuli, Sakuranetin strongly induced adipogenesis and expression of genes that are critical for the adipocytes phenotype. Time-course analyses indicated that Sakuranetin induces PPARgamma2 expression without prior induction of C/EBPbeta, a transcriptional regulator of PPARgamma2 in adipogenesis. In 3T3-L1 preadipocytes, the transcriptional factors GATA-2 and GATA-3 are known to down-regulate adipogenesis by direct binding to the C/EBPbeta protein and to the GATA-binding site on the PPARgamma2 promoter. We found that Sakuranetin significantly reduced the expression of GATA-2. Moreover, we observed that Sakuranetin stimulated glucose uptake in differentiated 3T3-L1 adipocytes.
CONCLUSIONS:
These results suggest that Sakuranetin may contribute to maintain glucose homeostasis in animals.

Antimutagenic Activity of Sakuranetin from Prunus Jamasakura.[Reference: WebLink]

J. Food Sci., 2003, 68(68):52-6.

Sakuranetin (compound 1) from bark of Prunus jamasakura showed a suppressive effect on umu gene expression of SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen furylfuramide.
METHODS AND RESULTS:
Gene expression was suppressed 83% at a concentration of 0.70 μmol/mL. The ID50 value of compound 1 was 0.30 μmol/mL. This compound showed the suppression of 4NQO, MNNG, Trp-P-1, AfB1, activated Trp-P-1, and UV irradiation-induced SOS response. The methylated derivative (compound 2) of compound 1 showed less suppressive effect against all mutagens than compound 1. The antimutagenic activities of compounds 1 and 2 against furylfuramide, Trp-P-1, and activated Trp-P-1 were assayed by the Ames test using the S. typhimurium TA100 strain.

Sakuranetin reverses vascular peribronchial and lung parenchyma remodeling in a murine model of chronic allergic pulmonary inflammation.[Pubmed: 27425653 ]

Acta Histochem. 2016 Jul;118(6):615-624.

Asthma is a disease of high prevalence and morbidity that generates high costs in hospitalization and treatment. Although the airway is involved in the physiopathology of asthma, there is also evidence of the importance of vascular and lung parenchyma inflammation and remodeling, which can contribute to the functional pulmonary alterations observed in asthmatic patients. Our aim was to evaluate treatment using Sakuranetin, a flavone isolated from the twigs of Baccharis retusa (Asteraceae), on vascular and lung parenchyma alterations in an experimental murine model of asthma.
METHODS AND RESULTS:
Male BALB/c mice were subjected to a sensitization protocol with ovalbumin for 30days and were treated with or without Sakuranetin (20mg/kg/mice) or dexamethasone (5mg/kg/mice); then, the lungs were collected for histopathological analysis. We evaluated extracellular matrix remodeling (collagen and elastic fibers), inflammation (eosinophils and NF-kB) and oxidative stress (8-isoprostane) in the pulmonary vessels and lung parenchyma. The thickness of the vascular wall was quantified, as well as the vascular endothelial growth factor (VEGF) levels. We demonstrated that Sakuranetin reduced the number of eosinophils and elastic fibers in both the pulmonary vessels and the lung parenchyma, probably due to a reduction of oxidative stress and of the transcription factor NF-kB and VEGF levels in the lung. In addition, it reduced the thickness of the pulmonary vascular wall. The treatment had no effect on the collagen fibers. In most of the parameters, the effect of Sakuranetin was similar to the dexamethasone effect.
CONCLUSIONS:
Sakuranetin had anti-inflammatory and antioxidant effects, preventing vascular and distal parenchyma changes in this experimental model of asthma.

Sakuranetin Induces Melanogenesis in B16BL6 Melanoma Cells through Inhibition of ERK and PI3K/AKT Signaling Pathways.[Pubmed: 27000529]

Phytother Res. 2016 Jun;30(6):997-1002.

Asthma is a disease of high prevalence and morbidity that generates high costs in hospitalization and treatment. Although the airway is involved in the physiopathology of asthma, there is also evidence of the importance of vascular and lung parenchyma inflammation and remodeling, which can contribute to the functional pulmonary alterations observed in asthmatic patients. Our aim was to evaluate treatment using Sakuranetin, a flavone isolated from the twigs of Baccharis retusa (Asteraceae), on vascular and lung parenchyma alterations in an experimental murine model of asthma.
METHODS AND RESULTS:
Male BALB/c mice were subjected to a sensitization protocol with ovalbumin for 30days and were treated with or without Sakuranetin (20mg/kg/mice) or dexamethasone (5mg/kg/mice); then, the lungs were collected for histopathological analysis. We evaluated extracellular matrix remodeling (collagen and elastic fibers), inflammation (eosinophils and NF-kB) and oxidative stress (8-isoprostane) in the pulmonary vessels and lung parenchyma. The thickness of the vascular wall was quantified, as well as the vascular endothelial growth factor (VEGF) levels. We demonstrated that Sakuranetin reduced the number of eosinophils and elastic fibers in both the pulmonary vessels and the lung parenchyma, probably due to a reduction of oxidative stress and of the transcription factor NF-kB and VEGF levels in the lung. In addition, it reduced the thickness of the pulmonary vascular wall. The treatment had no effect on the collagen fibers. In most of the parameters, the effect of Sakuranetin was similar to the dexamethasone effect.
CONCLUSIONS:
Sakuranetin had anti-inflammatory and antioxidant effects, preventing vascular and distal parenchyma changes in this experimental model of asthma.

Molecules. 2014 Jun 6;19(6):7528-42.

Structural crystalline characterization of sakuranetin--an antimicrobial flavanone from twigs of Baccharis retusa (Asteraceae).[Pubmed: 24914898]

Bioactivity-guided fractionation of an antimicrobial active extract from twigs of Baccharis retusa C. DC. (Asteraceae) yielded the flavanone 5,4'-dihydroxy-7-methoxy-flavanone (Sakuranetin) as responsible for the detected activity.
METHODS AND RESULTS:
The structure of the bioactive compound was established on the basis of spectroscopic data analysis, including NMR and MS. Additionally, the structure of a new crystal form of Sakuranetin was confirmed by X-ray diffratometry. The minimum inhibitory concentrations (MIC) of isolated compound were determined against pathogenic yeast belonging to the genus Candida (six species), Cryptococcus (two species/four serotypes) and S. cerevisiae BY 4742 (S288c background) and ranged from 0.32 to 0.63 μg/μL.
CONCLUSIONS:
Our results showed that Sakuranetin, which structure was fully characterized, could be used as a tool for the design of novel and more efficacious antifungal agents.

Bioengineered. 2012 Nov-Dec;3(6):352-7.

The potential bioproduction of the pharmaceutical agent sakuranetin, a flavonoid phytoalexin in rice.[Pubmed: 22895058]

Sakuranetin, the major flavonoid phytoalexin in rice, can be induced by ultraviolet (UV) irradiation, treatment with CuCl 2 or jasmonic acid (JA), or phytopathogenic infection. In addition to Sakuranetin's biological significance on disease resistance in rice, its broad bioactivities have recently been described.
METHODS AND RESULTS:
Results from these studies have shown that Sakuranetin is a useful compound as a plant antibiotic and a potential pharmaceutical agent. Sakuranetin is biosynthesized from naringenin, a precursor of Sakuranetin, by naringenin 7-O-methyltransferase (NOMT), but the relevant gene has not yet been identified in rice. Recently, we identified the OsNOMT gene, which is involved in the final step of Sakuranetin biosynthesis in rice. In previous studies, OsNOMT was purified to apparent homogeneity from UV-treated wild-type rice leaves; however, the purified protein, termed OsCOMT1, exhibited caffeic acid 3-O-methyltransferase (COMT) activity, but not NOMT activity. Based on the analysis of an oscomt1 T-DNA tagged mutant, we determined that OsCOMT1 did not contribute to Sakuranetin production in rice in vivo. Gene expression was induced by treatment with jasmonic acid in rice leaves prior to Sakuranetin accumulation, and the recombinant protein showed reasonable kinetic properties to NOMT.
CONCLUSIONS:
Identification of the OsNOMT gene enables the production of large amounts of Sakuranetin through transgenic rice and microorganisms. This finding also allows for the generation of disease-resistant and Sakuranetin biofortified rice in the future.