(RS)-Sakuranetin

Phenolic-Rich Extracts from Avocado Fruit Residues as Functional Food Ingredients with Antioxidant and Antiproliferative Properties.[Pubmed:34356601]

Biomolecules. 2021 Jul 2;11(7). pii: biom11070977.

In this study, the total phenolic compounds content and profile, the nutritional value, the antioxidant and antiproliferative activities of avocado peel, seed coat, and seed extracts were characterized. Additionally, an in-silico analysis was performed to identify the phenolic compounds with the highest intestinal absorption and Caco-2 permeability. The avocado peel extract possessed the highest content of phenolic compounds (309.95 +/- 25.33 mMol GA/100 g of extract) and the lowest effective concentration (EC50) against DPPH and ABTS radicals (72.64 +/- 10.70 and 181.68 +/- 18.47, respectively). On the other hand, the peel and seed coat extracts had the lowest energy densities (226.06 +/- 0.06 kcal/100 g and 219.62 +/- 0.49 kcal/100 g, respectively). Regarding the antiproliferative activity, the avocado peel extract (180 +/- 40 microg/mL) showed the lowest inhibitory concentration (IC50), followed by the seed (200 +/- 21 microg/mL) and seed coat (340 +/- 32 microg/mL) extracts. The IC50 of the extracts induced apoptosis in Caco-2 cells at the early and late stages. According to the in-silico analysis, these results could be related to the higher Caco-2 permeability to hydroxysalidroside, salidroside, sakuranetin, and luteolin. Therefore, this study provides new insights regarding the potential use of these extracts as functional ingredients with antioxidant and antiproliferative properties and as medicinal agents in diseases related to oxidative stress such as cancer.

Effects of Chemopreventive Natural Compounds on the Accuracy of 8-oxo-7,8-dihydro-2'-deoxyguanosine Translesion Synthesis.[Pubmed:34237787]

Planta Med. 2021 Aug;87(10-11):868-878.

Translesion synthesis is a DNA damage tolerance mechanism that relies on a series of specialized DNA polymerases able to bypass a lesion on a DNA template strand during replication or post-repair synthesis. Specialized translesion synthesis DNA polymerases pursue replication by inserting a base opposite to this lesion, correctly or incorrectly depending on the lesion nature, involved DNA polymerase(s), sequence context, and still unknown factors. To measure the correct or mutagenic outcome of 8-oxo-7,8-dihydro-2'-deoxyguanosine bypass by translesion synthesis, a primer-extension assay was performed in vitro on a template DNA bearing this lesion in the presence of nuclear proteins extracted from human intestinal epithelial cells (FHs 74 Int cell line); the reaction products were analyzed by both denaturing capillary electrophoresis (to measure the yield of translesion elongation) and pyrosequencing (to determine the identity of the nucleotide inserted in front of the lesion). The influence of 14 natural polyphenols on the correct or mutagenic outcome of translesion synthesis through 8-oxo-7,8-dihydro-2'-deoxyguanosine was then evaluated in 2 experimental conditions by adding the polyphenol either (i) to the reaction mix during the primer extension assay; or (ii) to the culture medium, 24 h before cell harvest and nuclear proteins extraction. Most of the tested polyphenols significantly influenced the outcome of translesion synthesis, either through an error-free (apigenin, baicalein, sakuranetin, and myricetin) or a mutagenic pathway (epicatechin, chalcone, genistein, magnolol, and honokiol).

Molecular docking analysis of stachydrine and sakuranetin with IL-6 and TNF-alpha in the context of inflammation.[Pubmed:34234397]

Bioinformation. 2021 Feb 28;17(2):363-368.

Inflammation is a process triggered by pro-inflammatory cytokines and anti-inflammatory molecules. Therefore, it is of interest to document the anti-inflammatory activity of Stachydrine and Sakuranetin against the inflammatory target proteins IL-6 and TNF-alpha by using molecular docking analysis. Both compounds showed good binding features with the selected target proteins. Compared to Sakuranetin, the Stachydrine have low binding energy and good hydrogen bond interactions. Hence, data show that Stachydrine possessed high and specific inhibitory activity on tumor necrosis factor-alpha and interleukin-6.

[Analysis of differences between unifloral honeys from different botanical origins based on non-targeted metabolomics by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry].[Pubmed:34227310]

Se Pu. 2021 Mar;39(3):291-300.

Different nectar plants contain various secondary metabolites. Herein, the differences in the contents of endogenous metabolites in honeys from eight botanical origins (i. e., acacia, jujube, vitex, linden, buckwheat, manuka, wolfberry, and motherwort honeys) were investigated by a non-targeted metabolomics-based method. This method involved solid-phase extraction pretreatment and ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS(E)). An oasis HLB cartridge was used for the removal of many saccharides. Chromatographic experiments were performed on an HSS T3 column (100 mmx2.1 mm, 1.8 mum) using a mobile phase that consisted of 0.1% (v/v) formic acid in acetonitrile and water. Mass spectrometry was conducted in the positive and negative modes by electrospray ionization (ESI). Metabolic information about the honeys from different botanical origins was acquired using a multivariate statistical analysis model. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) were conducted for pattern recognition and difference analysis. PCA was performed for 10557 and 2706 data variables in the positive and negative ion modes, respectively. The distribution of honeys from different botanical origins was investigated in 88 honey samples. The three principal components exhibited 48.05% and 57.88% of the total variance in positive and negative ion modes, respectively. The samples studied were divided into six different groups on the basis of their botanical origins and metabolic compounds: linden, vitex, buckwheat, manuka, jujube, and acacia honeys. A permutation test (n=200) was conducted to verify the fit of the model. The differential metabolites were screened on the basis of variable importance in project (VIP; >1), analysis of variance (ANOVA; p<0.05), and maximum fold change (>1.5) by using the PLS-DA model. The compounds were identified based on the data retrieved from the Chemspider and HMDB databases according to the quality information of precursor ions and fragment ions. Thirty-two differential metabolites were screened and primarily identified according to the characteristic fragmentation rules of specific structure types and data retrieval, including 18 flavonoids, 7 phenolic acids, 6 phenyl and terpenoid glycosides, and 1 steroid. Various flavonoids in buckwheat and manuka honeys, such as quercetin, sakuranetin, 7-hydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-4H-chromen-4-one, 5,7-dihydroxy-2-(3-methoxyphenyl)-4H-chromen-4-one, luteolin-7-methyl ether, and pollenitin, were found. In buckwheat honey, the contents of 3-methoxy-2-(4-methylbenzoyl)-4H-chromen-4-one, 2-hydroxy-3,4-diphenylpentanedioic acid, 3'-methoxydihydroformononetin, phenylpyruvic acid, 2-O-p-coumaroyltartronic acid, 2-(3-hydroxy-4,5-dimethoxyphenyl)-4H-chromen-4-one, 7-hydroxy-6-methoxy-3-(4-methoxyphenyl)-4H-chromen-4-one, 4-[(2E)-3-(4-hydroxyphenyl)prop-2-en-1-yl]-3-methoxyphenol, and 7-hydroxy-5-methoxyflavan were the highest; these compounds are the characteristic metabolites of buckwheat honey. In addition, manuka honey possessed the highest contents of gnaphaliin and galangin 3-methyl ether. Moreover, linden honey contained the characteristic phenyl glycosides of (S)-multifidol 2-[apiosyl-(16)-glucoside], 2-phenylethyl-beta-D-glucopyranoside, benzyl O-[arabinofuranosyl-(16)-glucoside], crosatoside B, and terpenoid glycosides of isopentyl gentiobioside and 6-O-oleuropeoylsucrose. Vitex honey was found to be rich in quinic acid derivatives such as caffeoyl-3-O-feruloyl-quinic acid/1-feruloyl-5-caffeoylquinic acid, 3-O-caffeoyl-4-O-methyl-quinic acid/3-feruloylquinic acid, and 3-O-caffeoyl-1-O-methyl-quinic acid, in addition to the flavonoids of vitexin, namely, 6''-(3-hydroxy-3-methylglutarate) and apigenin-7-[galactosyl-(14)-mannoside]. Moreover, ponasteroside A was a characteristic marker of jujube honey, and the contents of 6-C-fucosylluteolin and kaempferol 3-(2''-rhamnosylrutinoside) were the highest in acacia honey. In conclusion, the method based on non-targeted metabolomics involving UPLC-Q-TOF-MS(E) for different unifloral honeys was found to be fast, effective, specific, and accurate. The differences in metabolite contents and the characteristic compounds in various unifloral honeys were preliminarily illustrated. This study provides an effective analytical strategy for honey traceability and quality analysis of unifloral honey.

Antioxidant and antimicrobial activities and UPLC-ESI-MS/MS polyphenolic profile of sweet orange peel extracts.[Pubmed:34124691]

Curr Res Food Sci. 2021 May 26;4:326-335.

With growing consumer awareness, exploitation of renewable resources is cost-effective and environment friendly. This work examines the potential of citrus peels as natural antioxidants and antimicrobials for food preservation. Extraction yield, total soluble phenols and flavonoids of various citrus peels (sweet orange, lemon, tangerine and grapefruit) were optimized by varying the solvent type. While the highest extract yield (~16 g/100g) was obtained from the sweet orange peels in methanol, extraction with ethanol maximized the concentration of total phenols and flavonoids (~80 mg catechol equivalents/100 g dry weight). In addition, sweet orange peel extract showed the highest DPPH, ABTS and hydroxyl radical scavenging values. UPLC-ESI-MS/MS analysis of aqueous and ethanolic extracts of sweet orange peels revealed more than 40 polyphenolic compounds including phenolic acids and flavonoids, some of which have not been previously reported. The predominant polyphenols were narirutin, naringin, hesperetin-7-O-rutinoside naringenin, quinic acid, hesperetin, datiscetin-3-O-rutinoside and sakuranetin. The incorporation of sweet orange peel extract into two vegetable oils enhanced their oxidative stability. In addition, all citrus peel extracts possessed high antimicrobial activity against several food-borne pathogens, and the activity was highest for the sweet orange peel extract. Overall results suggested the great potential of sweet orange peels as natural antioxidant and antimicrobials, which can be efficiently extracted using a simple and low-cost method, for enhancing the storage stability and safety of vegetable oils.

Genetic mapping identifies a rice naringenin O-glucosyltransferase that influences insect resistance.[Pubmed:33745166]

Plant J. 2021 Jun;106(5):1401-1413.

Naringenin, the biochemical precursor for predominant flavonoids in grasses, provides protection against UV damage, pathogen infection and insect feeding. To identify previously unknown loci influencing naringenin accumulation in rice (Oryza sativa), recombinant inbred lines derived from the Nipponbare and IR64 cultivars were used to map a quantitative trait locus (QTL) for naringenin abundance to a region of 50 genes on rice chromosome 7. Examination of candidate genes in the QTL confidence interval identified four predicted uridine diphosphate-dependent glucosyltransferases (Os07g31960, Os07g32010, Os07g32020 and Os07g32060). In vitro assays demonstrated that one of these genes, Os07g32020 (UGT707A3), encodes a glucosyltransferase that converts naringenin and uridine diphosphate-glucose to naringenin-7-O-beta-d-glucoside. The function of Os07g32020 was verified with CRISPR/Cas9 mutant lines, which accumulated more naringenin and less naringenin-7-O-beta-d-glucoside and apigenin-7-O-beta-d-glucoside than wild-type Nipponbare. Expression of Os12g13800, which encodes a naringenin 7-O-methyltransferase that produces sakuranetin, was elevated in the mutant lines after treatment with methyl jasmonate and insect pests, Spodoptera litura (cotton leafworm), Oxya hyla intricata (rice grasshopper) and Nilaparvata lugens (brown planthopper), leading to a higher accumulation of sakuranetin. Feeding damage from O. hyla intricata and N. lugens was reduced on the Os07g32020 mutant lines relative to Nipponbare. Modification of the Os07g32020 gene could be used to increase the production of naringenin and sakuranetin rice flavonoids in a more targeted manner. These findings may open up new opportunities for selective breeding of this important rice metabolic trait.

[A novel flavanone from Thymus przewalskii].[Pubmed:33645061]

Zhongguo Zhong Yao Za Zhi. 2021 Jan;46(1):125-129.

This study was to investigate the chemical constituents from the aerial parts of Thymus przewalskii. The chemical consti-tuents were separated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and semi-prepared HPLC, and their structures were determined by physicochemical properties and spectroscopic data. Four flavanones were isolated from the ethanol extract of the aerial parts of T. przewalskii, and identified as(2S)-5,6-dihydroxy-7,8,4'-trimethoxyflavanone(1), 5,4'-dihydroxy-6,7-dimethoxyflavanone(2),(2S)-5,4'-dihydroxy-7,8-dimethoxyflavano ne(3), sakuranetin(4), respectively. Compound 1 was a new compound and its configuration was determined by CD spectrum, compound 3 was natural product which was isolated for the first time and their configurations were determined by CD spectra. Compound 2 was isolated from the genus Thymus for the first time and compound 4 was isolated from T. przewalskii for the first time. Furthermore, cytotoxicity test was assayed for the four flavanones. They exhibited weak cytotoxicity against human lung cancer cells(A549), with the IC_(50) from 74.5 to 135.6 mumol.L~(-1).

Phenolic Profile and Bioactive Potential of Stems and Seed Kernels of Sweet Cherry Fruit.[Pubmed:33348687]

Antioxidants (Basel). 2020 Dec 17;9(12). pii: antiox9121295.

Every year, large quantities of stems and pits are generated during sweet cherry processing, without any substantial use. Although stems are widely recognized by traditional medicine, detailed and feasible information about their bioactive composition or biological value is still scarce, as well as the characterization of kernels. Therefore, we conducted a study in which bioactivity potential of extracts from stems and kernels of four sweet cherry cultivars (Early Bigi (grown under net cover (C) and without net cover (NC)), Burlat, Lapins, and Van) were examined. The assays included antioxidant (by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and beta-carotene-linoleic acid bleaching assays), and antibacterial activities against important Gram negative and Gram positive bacterial human isolates. Profile and individual phenolic composition of each extract were determined by High-performance liquid chromatography (HPLC) analysis. Extracts from stems of cv. Lapins and kernels of Early Bigi NC presented high levels of total phenolics, flavonoids, ortho-diphenols and saponins. Excepting for cv. Early Bigi NC, major phenolic compounds identified in stems and kernels were sakuranetin and catechin, respectively. In cv. Early Bigi NC the most abundant compounds were ellagic acid for stems and protocatechuic acid for kernels. In all extracts, antioxidant activities showed a positive correlation with the increments in phenolic compounds. Antimicrobial activity assays showed that only stem's extracts were capable of inhibiting the growth of Gram positive isolates. This new data is intended to provide new possibilities of valorization of these by-products and their valuable properties.

Biochemical Characterization of a Flavonoid O-methyltransferase from Perilla Leaves and Its Application in 7-Methoxyflavonoid Production.[Pubmed:32998370]

Molecules. 2020 Sep 28;25(19). pii: molecules25194455.

Methylation is a common structural modification that can alter and improve the biological activities of natural compounds. O-Methyltransferases (OMTs) catalyze the methylation of a wide array of secondary metabolites, including flavonoids, and are potentially useful tools for the biotechnological production of valuable natural products. An OMT gene (PfOMT3) was isolated from perilla leaves as a putative flavonoid OMT (FOMT). Phylogenetic analysis and sequence comparisons showed that PfOMT3 is a class II OMT. Recombinant PfOMT3 catalyzed the methylation of flavonoid substrates, whereas no methylated product was detected in PfOMT3 reactions with phenylpropanoid substrates. Structural analyses of the methylation products revealed that PfOMT3 regiospecifically transfers a methyl group to the 7-OH of flavonoids. These results indicate that PfOMT3 is an FOMT that catalyzes the 7-O-methylation of flavonoids. PfOMT3 methylated diverse flavonoids regardless of their backbone structure. Chrysin, naringenin and apigenin were found to be the preferred substrates of PfOMT3. Recombinant PfOMT3 showed moderate OMT activity toward eriodictyol, luteolin and kaempferol. To assess the biotechnological potential of PfOMT3, the biotransformation of flavonoids was performed using PfOMT3-transformed Escherichia coli. Naringenin and kaempferol were successfully bioconverted to the 7-methylated products sakuranetin and rhamnocitrin, respectively, by E. coli harboring PfOMT3.

Exogenous abscisic acid induces the lipid and flavonoid metabolism of tea plants under drought stress.[Pubmed:32704005]

Sci Rep. 2020 Jul 23;10(1):12275.

Abscisic acid (ABA) is an important phytohormone responsible for activating drought resistance, but the regulation mechanism of exogenous ABA on tea plants under drought stress was rarely reported. Here, we analyzed the effects of exogenous ABA on genes and metabolites of tea leaves under drought stress using transcriptomic and metabolomic analysis. The results showed that the exogenous ABA significantly induced the metabolic pathways of tea leaves under drought stress, including energy metabolism, amino acid metabolism, lipid metabolism and flavonoids biosynthesis. In which, the exogenous ABA could clearly affect the expression of genes involved in lipid metabolism and flavonoid biosynthesis. Meanwhile, it also increased the contents of flavone, anthocyanins, flavonol, isoflavone of tea leaves under drought stress, including, kaempferitrin, sakuranetin, kaempferol, and decreased the contents of glycerophospholipids, glycerolipids and fatty acids of tea leaves under drought stress. The results suggested that the exogenous ABA could alleviate the damages of tea leaves under drought stress through inducing the expression of the genes and altering the contents of metabolites in response to drought stress. This study will be helpful to understand the mechanism of resilience to abiotic stress in tea plant and provide novel insights into enhancing drought tolerance in the future.

Chemical Fingerprinting, Isolation and Characterization of Polyphenol Compounds from Heliotropium taltalense (Phil.) I.M. Johnst and Its Endothelium-Dependent Vascular Relaxation Effect in Rat Aorta.[Pubmed:32650373]

Molecules. 2020 Jul 8;25(14). pii: molecules25143105.

Heliotropium taltalense is an endemic species of the northern coast of Chile and is used as folk medicine. The polyphenolic composition of the methanolic and aqueous extract of the endemic Chilean species was investigated using Ultrahigh-Performance Liquid Chromatography, Heated Electrospray Ionization and Mass Spectrometry (UHPLC-Orbitrap-HESI-MS). Fifty-three compounds were detected, mainly derivatives of benzoic acid, flavonoids, and some phenolic acids. Furthermore, five major compounds were isolated by column chromatography from the extract, including four flavonoids and one geranyl benzoic acid derivative, which showed vascular relaxation and were in part responsible for the activity of the extracts. Since aqueous extract of H. taltalense (83% +/- 9%, 100 mug/mL) produced vascular relaxation through an endothelium-dependent mechanism in rat aorta, and the compounds rhamnocitrin (89% +/- 7%; 10(-4) M) and sakuranetin (80% +/- 6%; 10(-4) M) also caused vascular relaxation similar to the extracts of H. taltalense, these pure compounds are, to some extent, responsible for the vascular relaxation.

Two Chalcone Synthase Isozymes Participate Redundantly in UV-Induced Sakuranetin Synthesis in Rice.[Pubmed:32471084]

Int J Mol Sci. 2020 May 27;21(11). pii: ijms21113777.

: Chalcone synthase (CHS) is a key enzyme in the flavonoid pathway, participating in the production of phenolic phytoalexins. The rice genome contains 31 CHS family genes (OsCHSs). The molecular characterization of OsCHSs suggests that OsCHS8 and OsCHS24 belong in the bona fide CHSs, while the other members are categorized in the non-CHS group of type III polyketide synthases (PKSs). Biochemical analyses of recombinant OsCHSs also showed that OsCHS24 and OsCHS8 catalyze the formation of naringenin chalcone from p-coumaroyl-CoA and malonyl-CoA, while the other OsCHSs had no detectable CHS activity. OsCHS24 is kinetically more efficient than OsCHS8. Of the OsCHSs, OsCHS24 also showed the highest expression levels in different tissues and developmental stages, suggesting that it is the major CHS isoform in rice. In oschs24 mutant leaves, sakuranetin content decreased to 64.6% and 80.2% of those in wild-type leaves at 2 and 4 days after UV irradiation, respectively, even though OsCHS24 expression was mostly suppressed. Instead, the OsCHS8 expression was markedly increased in the oschs24 mutant under UV stress conditions compared to that in the wild-type, which likely supports the UV-induced production of sakuranetin in oschs24. These results suggest that OsCHS24 acts as the main CHS isozyme and OsCHS8 redundantly contributes to the UV-induced production of sakuranetin in rice leaves.

Antiprotozoal Activity against Entamoeba histolytica of Flavonoids Isolated from Lippia graveolens Kunth.[Pubmed:32466359]

Molecules. 2020 May 26;25(11). pii: molecules25112464.

Amebiasis caused by Entamoeba histolytica is nowadays a serious public health problem worldwide, especially in developing countries. Annually, up to 100,000 deaths occur across the world. Due to the resistance that pathogenic protozoa exhibit against commercial antiprotozoal drugs, a growing emphasis has been placed on plants used in traditional medicine to discover new antiparasitics. Previously, we reported the in vitro antiamoebic activity of a methanolic extract of Lippia graveolens Kunth (Mexican oregano). In this study, we outline the isolation and structure elucidation of antiamoebic compounds occurring in this plant. The subsequent work-up of this methanol extract by bioguided isolation using several chromatographic techniques yielded the flavonoids pinocembrin (1), sakuranetin (2), cirsimaritin (3), and naringenin (4). Structural elucidation of the isolated compounds was achieved by spectroscopic/spectrometric analyses and comparing literature data. These compounds revealed significant antiprotozoal activity against E. histolytica trophozoites using in vitro tests, showing a 50% inhibitory concentration (IC50) ranging from 28 to 154 microg/mL. Amebicide activity of sakuranetin and cirsimaritin is reported for the first time in this study. These research data may help to corroborate the use of this plant in traditional Mexican medicine for the treatment of dyspepsia.

Flavonoids from Varronia dardani (Taroda) J.S. Mill (cordiaceae) and the evaluation of spasmolytic activity of its crude ethanolic extract.[Pubmed:32338066]

Nat Prod Res. 2020 Apr 27:1-5.

Pharmacological studies show spasmolytic activity for various species of Varronia. Thus, based on the taxonomy criteria, the aim of this study was to contribute to chemical and biological knowledge, especially regarding the evaluation of spasmolytic activity of the ethanolic extract from Varronia dardani leaves (VD-EtOHL) on rat aorta and trachea, guinea-pig ileum and rat uterus. Were used High and Medium Performance Liquid Chromatography. Wistar rats and guinea-pigs were used for pharmacological assays. All experimental protocols were approved by Animal Ethics Committee of UFPB (126/2017). Two chalcones (pinostrobin chalcone and gymnogrammene), five flavanones (pinocembrin, isosakuranetin, pinostrobin, sakuranetin 4'-methyl ether, naringenin) and a flavonoid glycosilated (astragalin) were identified based on data of (1)H and (13)C Nuclear Magnetic Resonance. This study also showed that VD-EtOHL has a non-selective spasmolytic activity, presenting greater relaxing potency in rat uterus, suggesting that flavonoids isolated from VD-EtOHL may be responsible for spasmolytic activity of this extract.