Prominent Flavonoids Research Articles

Molecular Docking Approach to Identify Flavonoids as Potential Phosphodiesterase 5 Inhibitors for Erectile Dysfunction Treatment

An erection that is not strong enough for sexual activity might be caused by erectile dysfunction. Periodically experiencing difficulties achieving an erection is not always a reason for alarm. On the other hand, if erectile dysfunction persists, it may lead to stress, undermine confidence, and exacerbate interpersonal issues. In addition to being a risk factor for heart disease, difficulties achieving or maintaining an erection may also indicate an underlying medical issue that needs to be treated. Many studies have also steadily examined flavonoids' capacity to inhibit the phosphodiesterase 5 enzyme in several recent studies. This is an enzyme expressed in erectile tissue that is the most important substance that degrades cGMP in the body's smooth muscle cells. This study identified two prominent flavonoids that had inhibitory effects on the phosphodiesterase 5 enzyme: Amenoflavone and Umbralisib. Our research suggests new molecular pathways by which these substances might influence biological processes. One compound that shows promise for treating erectile dysfunction and is safe for healthy cells is Amentoflavone.

Mechanistic study on vasodilatory and antihypertensive effects of hesperetin: ex vivo and in vivo approaches.

Hesperetin is one of the prominent flavonoids found in citrus fruit. Several research studies have reported that hesperetin can promote vasodilation in vascular tissue by increasing the level of nitric oxide and cyclic nucleotides. However, these may not be the only pathway for hesperetin to exert its vasodilatory effect. In addition to vasodilation, hesperetin has been found to carry an antihypertensive effect through intraperitoneal injection, although no study has comprehensively investigated the antihypertensive effect of hesperetin through oral administration. Therefore, this study aimed to determine the possible mechanism pathways involved in hesperetin-induced vasodilation and investigated its antihypertensive effects on hypertensive rats' model via oral administration. The ex vivo experimental findings showed that the NO/sGC/cGMP signalling pathway was involved in hesperetin-mediated vasodilation. Moreover, hesperetin activated the AC/cAMP/PKA pathway through PGI2 and activated the β2-adrenergic receptor. Hesperetin can act as a voltage-gated potassium channel (KV) and ATP-sensitive potassium channel (KATP) opener. The intracellular calcium in vascular smooth muscle was reduced by hesperetin through blocking the voltage-operated calcium channels (VOCC) and inositol triphosphate receptor (IP3R). In the in vivo assessment, hesperetin shows a significant decrease in Spontaneously Hypertensive rats' blood pressure following 21 days of oral treatment. The sub-chronic toxicity assessment demonstrated that hesperetin exhibited no deleterious effects on the body weights, clinical biochemistry and haematological profile of Sprague-Dawley rats. This study implies that hesperetin holds promise as a potential medication for hypertension treatment, devoid of undesirable side effects.

Aspalathin, a Primary Rooibos Flavonoid, Alleviates Mast Cell-Mediated Allergic Inflammation by the Inhibition of FcεRI Signaling Pathway.

Mast cells are primary cells initiating allergic inflammation by the release of various allergic mediators, such as histamine and pro-inflammatory cytokines. Aspalathin (ASP) is the predominant flavonoid found exclusively in rooibos, an herb that has been traditionally used in allergy relief therapy. In the present study, we investigated the beneficial effects of ASP on mast cell-mediated allergic inflammation. For in vivo study, two well-known mast cell-mediated local and systemic allergic inflammation mouse models were used: passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis mouse models (ASA). Oral administration of ASP dose-dependently suppressed immunoglobulin (Ig)E-mediated PCA responses evidenced by Evans blue extravasation, ear thickening, and mast cell degranulation. ASP also significantly mitigated ovalbumin-induced ASA responses, including hypothermia, histamine secretion, and the production of IgE and interleukin-4. Notably, ASP was more effective in suppressing allergic inflammation than nothofagin, another prominent flavonoid known as an anti-allergic component of rooibos. The regulatory mechanism of mast cell activation by ASP was clarified using mast cell line and primary cultured mast cells (RBL-2H3 and mouse bone marrow-derived mast cells). ASP reduced IgE-stimulated mast cells degranulation and intracellular calcium influx by the inhibition of FcεRI signaling pathway (Lyn, Fyn, and Syk). Moreover, ASP reduced pro-inflammatory cytokine expressions by inhibiting two major transcription factors, nuclear factor of activated T cells and nuclear factor-κB. Collectively, we proposed that ASP could be a potential therapeutic candidate for the treatment of mast cell-mediated allergic inflammatory diseases.

Anti-Aging Potential of the Two Major Flavonoids Occurring in Asian Water Lily Using In Vitro and In Silico Molecular Modeling Assessments.

Our previous study investigated the major flavonoids and antioxidant potential of Asian water lily (Nymphaea lotus L., family Nymphaeaceae) stamens and perianth extracts. Quercetin-3-O-rhamnoside (Que-3-Rha) and kaempferol-3-O-galactoside (Kae-3-Gal) were reported as the two most prominent flavonoids found in these extracts. Many flavonoids have been reported on the skin anti-aging effect that are useful for cosmeceutical/phytopharmaceutical application. However, Que-3-Rha and Kae-3-Gal occurring in this medicinal plant have not yet been evaluated for their ability to inhibit skin-aging enzymes. Therefore, this study aimed (1) to assess the enzyme inhibitory activity of Que-3-Rha and Kae-3-Gal, and (2) to conduct molecular modeling of these compounds against critical enzymes involved in skin aging such as collagenase, elastase, and tyrosinase. In vitro enzymatic assays demonstrated that both of the two most prominent flavonoids exhibited moderate to good inhibitory activity toward these enzymes. These experimental findings were supported by molecular docking analysis, which indicated that Que-3-Rha and Kae-3-Gal showed superior binding affinity to the target enzymes compared to the positive controls. Additionally, computational predictions suggested favorable skin permeability and no severe toxicity for both compounds. The results from molecular dynamic (MD) simulation revealed that all the complexes remained stable during the 200 ns MD simulation. Structural analyses and binding free energy calculations also supported the inhibitory potential of these two flavonoids against skin-aging enzymes. In conclusion, this study provides valuable insights into the anti-aging potential of the two major flavonoids occurring in this medicinal plant, paving the way for further development of cosmeceutical/phytopharmaceutical products targeting skin aging.

Icariside Ⅱ attenuates bleomycin-induced pulmonary fibrosis by modulating macrophage polarization

Ethnopharmacological relevanceNumerous studies have provided evidence supporting the significant roles of icariin, in the prevention of multiple chronic diseases like diabetes, liver fibrosis, cardiac fibrosis, renal fibrosis, and pulmonary fibrosis. In particular, Icariside II (ISE II), a prominent flavonoid glycoside derived from Epimedium brevicornum Maxim, the principal metabolite of icariin, has demonstrated noteworthy anti-inflammatory and anti-oxidant properties, along with its ability to protect against lung remodeling. However, the research exploring ISE Ⅱ's application in treating pulmonary fibrosis remains limited. Aim of the studyThe aim of this study was to assess the therapeutic efficacy of ISE II in models of pulmonary fibrosis, while also investigating its potential mechanisms of action in cell signaling pathways. Materials and methodsAn in vitro model of pulmonary fibrosis was established by treating NIH-3T3 cells with transforming growth factor-β1 (TGF-β1). Western blot, RT-qPCR, and scratch test were performed to assess the effect of ISE Ⅱ. In addition, a murine model of pulmonary fibrosis was induced by intratracheal instillation of bleomycin, and the therapeutic effect of ISE Ⅱ was tested by orally administering ISE Ⅱ at a dose of 10 mg/kg. Three weeks later, lung function, micro-CT, hydroxyproline content, pathological staining, and cytokines detection of BALF or serum were used to assess the anti-fibrosis effects of ISE Ⅱ. Next, immunofluorescence staining, flow cytometry, and in vivo transcriptomics were used to investigate the underlying mechanisms of action. ResultsOur data revealed a significant inhibitory effect of ISE Ⅱ on the upregulation of α-smooth muscle actin (α-SMA) and collagen production induced by TGF-β1 in fibroblasts. Meanwhile, ISE Ⅱ exerted a therapeutic effect against bleomycin-induced pulmonary fibrosis in mice by improving lung function, decreasing collagen deposition, and reducing the expression of interleukin (IL)-1β, tumor necrosis factor α (TNF-α), TGF-β1 and platelet-derived growth factor (PDGF) in serum and bronchoalveolar lavage fluid (BALF). Additionally, ISE Ⅱ treatment effectively attenuated the infiltration of M2 macrophages, concurrently downregulating the expression level of M2 marker genes, such as CD206, arginase-1(Arg-1), and Chitinase-Like Protein 3 (YM-1). Importantly, we observed a statistically significant reduction in the M2 phenotype of interstitial macrophages (IMs). However, the impact of ISE Ⅱ on the M2 polarization of alveolar macrophages (AMs) did not reach statistical significance. Lastly, transcriptome sequencing results suggested that the anti-pulmonary fibrosis effects of ISE Ⅱ may be mediated by the suppression of the WNT/β-catenin signaling pathway, which modulated M2 polarization in macrophages and contributed to the amelioration of pulmonary fibrosis. By immunohistochemical analysis, it was verified that ISE Ⅱ treatment dramatically inhibited the activation of β-catenin in fibrosis murine. ConclusionOur findings indicated that ISE Ⅱ exerted anti-fibrotic effects by inhibiting pro-fibrotic macrophage polarization. The underlying mechanism of action might be mediated by modulating the WNT/β-catenin signaling pathway to inhibit the M2 program in IMs.

Untargeted Metabolomics Based Prediction of Therapeutic Potential for Apigenin and Chrysin

The prominent flavonoids apigenin and chrysin have been demonstrated to have systemic benefits. Our previous work was first to establish the impact of apigenin and chrysin on cellular transcriptome. In the current study, we have revealed the ability of apigenin and chrysin to alter the cellular metabolome based on our untargeted metabolomics. Based on our metabolomics data, both these structurally related flavonoids demonstrate diverging and converging properties. Apigenin demonstrated the potential to possess anti-inflammatory and vasorelaxant properties through the upregulation of intermediate metabolites of alpha-linolenic acid and linoleic acid pathways. Chrysin, on the other hand, exhibited abilities to inhibit protein and pyrimidine synthesis along with downregulation of gluconeogenesis pathways based on the altered metabolites detected. Chrysin-mediated metabolite changes are mostly due to its ability to modulate L-alanine metabolism and the urea cycle. On the other hand, both the flavonoids also demonstrated converging properties. Apigenin and chrysin were able to downregulate metabolites involved in cholesterol biosynthesis and uric acid synthesis, namely 7-dehydrocholesterol and xanthosine, respectively. This work will provide understanding regarding the diverse therapeutic potential of these naturally occurring flavonoids and help us in curbing an array of metabolic complications.

Radical scavenging activities of Kaempferia larsenii Sirirugsa extract and prominent flavonoids in its rhizomes

Medicinal plants of the genus Kaempferia (Zingiberaceae) have long been valued in Thailand, where their fresh rhizomes, extracts and oils are utilized for traditional medicinal purposes. While the well-known Kaempferia plants, particularly K. galanga and K. parviflora have been scientifically proven to be effective medicinal herbs in antioxidative investigations and in a variety of pharmacological activities, K. larsenii, one of the members of this genus that is found in northeastern Thailand and has long been used by local practitioners for curative purposes, has never had the chemical constituents and antioxidant activity reported before. Thus, the purpose of this study was to determine the antioxidant capacity of the plant and the active chemical components accountable for its action. K. larsenii rhizome extract was subjected to a number of antioxidative tests, including 2,2?-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), 2,2-diphenyl-1-picrylhydrazyl, superoxide anion and hydroxyl radical scavenging activities, as well as HPLC analyses. The HPLC method used a ZORBAX Eclipse Plus C18 column, a 1 mL/min flow rate of methanol and 0.1% (v/v) phosphoric acid (55:45) and a diode-array UV absorbance at 265 nm as the stationary phase, mobile phase and detection respectively. In the investigated assays, the plant extract exhibited remarkable antioxidant activity, with EC50 values ranging from 11.60 to 26.31 µg/mL. Its efficacy was significantly higher than that of the positive controls, which had EC50 values ranging from 13.08 to 29.91 µg/mL. According to the HPLC profile of the extract, the medicinal flavonoids kaempferol and quercetin were present in the sample at % of 12.7562 and 0.4976 (w/w) respectively. K. larsenii rhizome extract is a good source of antioxidants and has the potential to be incorporated into herbal medicinal preparations that would be beneficial for health.

Baicalein Inhibits Metastatic Phenotypes in Nasopharyngeal Carcinoma Cells via a Focal Adhesion Protein Integrin β8.

Baicalein, a prominent flavonoid from the indigenous herbal plant Scutellaria baicalensis Georgi, possesses broad-spectrum anticancer activities. However, the biological effects of baicalein on nasopharyngeal carcinoma (NPC) and its underlying mechanisms remain unclarified. Thus, in this study, we examined the effects of baicalein on NPC cell lines and investigated the corresponding molecular mechanism through transcriptome profiling. In the study, four NPC cell lines were treated with various concentrations of baicalein at different time points. Cellular toxicity and proliferative inhibition of baicalein were examined by MTT assay. Metastatic phenotypes of NPC cells were investigated by wound healing, transwell, and adhesion assays. Additionally, microarray experiments were performed to determine the cellular pathways affected by baicalein. The expression and localization of the integrin β8 were validated by western immunoblotting and immunofluorescence. Our results revealed that baicalein exhibited its cytotoxicity and antiproliferative activity on all tested NPC cell lines. It also significantly inhibited metastatic phenotypes at sub-lethal concentrations. Transcriptomic analysis showed that baicalein significantly affected the focal adhesion pathway in NPC, where integrin β8 was greatly diminished. Thus, the present study results suggested that baicalein inhibits the metastatic phenotypes of NPC cells by modulating integrin β8, one of the major molecules in a focal adhesion pathway.

Naringenin as a Possible Candidate Against SARS-CoV-2 Infection and in the Pathogenesis of COVID-19

Naringenin, widely distributed in fruits and vegetables, is endowed with antiviral and other health beneficial activities, such as immune-stimulating and anti-inflammatory actions that could play a role in contributing, to some extent, to either preventing or alleviating coronavirus infection. Several computational studies have identified naringenin as one of the prominent flavonoids that can possibly inhibit internalization of the virus, virus-host interactions that trigger the cytokine storm, and replication of the virus. This review highlights the antiviral potential of naringenin in COVID-19 associated risk factors and its predicted therapeutic targets against SARS-CoV-2 infection.

α-Glucosidase Inhibitory Activity of Phenolic Rich Extracts Obtained from the Seeds of Melastoma saigonense (Kuntze) Merr.

The aim of this study was to perform a phytochemical analysis of Melastoma saigonense seed extracts and to determine their α-glucosidase inhibitory activity. The extracts from seeds of M. saigonense indicated that the total phenolic content was in the range between 233.46 and 967.22 mg GAE/g DE, whereas the flavonoids content was in the range between 359.96 and 850.84 mg QE/g DE. The present study of antidiabetic inhibitory activity by in vitro α-glucosidase revealed that the crude extracts using ethyl acetate (EA), butanol (BU) and final aqueous residue extracts (AQ) exhibited a strong α-glucosidase inhibitory effect (IC50 4.42-11.95 μg/mL). The ethyl acetate and butanol extracts of seeds of Melastoma saigonense (Kuntze) Merr. were further fractionated by silica gel column chromatography into four fractions (EAF1−EAF4) and five fractions (BUF1−BUF5), respectively and their bioactivities were investigated. The nine fractions exhibited significant α-glucosidase inhibitory activity (p < 0.05) with an IC50 between 3.42-34.77 μg/mL which is less than the IC50 for standard acarbose (IC50 = 507.26 μg/mL). Among all the fractions, BUF1 and EAF1 exhibited high inhibitory activity against α-glucosidase with BUF1 showing the highest inhibitory activity (IC50 = 3.42 μg/mL). The dominant phenolic acids were sinapic, gallic, ferrulic, syringic, gallic and caffeic acids and the prominent flavonoids were myricetin and quercetin. These findings suggest that the seeds of M. saigonense have potential as a source of antidiabetic agent (s).

An optimized solvent extraction and characterization of unidentified flavonoid glucuronide derivatives from spinach by UHPLC-HR-QTOF-MS

A rapid, sensitive analytical method using ultra-high-pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-HR-QTOF-MS) was developed for the identification and quantification of flavonoids from spinach. The extraction efficiency of flavonoids was evaluated by different solvents such as acetone, ethanol, methanol, acetone: water (70:30), ethanol: water (70:30) and methanol: water (70:30). Flavonoid identification was achieved by UV spectra, high resolution accurate mass and their fragmentation pattern. The precursor and product ions were recorded by both broadband collision ion dissociation (bbCID) and multiple reaction monitoring (MRM) techniques. Different collision energies (5, 10, 15, 20, 40, and 70 eV) were optimized to obtain the mass spectra of flavonoids in positive and negative ionization modes. For the first time, five minor flavonoid glucuronide derivatives were identified in spinach. MRM and bbCID provided glucuronide fingerprint ions at m/z 175.0278 and m/z 113.0257 respectively in negative ionization mode. The quantification of identified flavonoids was achieved by 5,3',4'-trihydroxy-3-methoxy-6:7-methylen-dioxyflavone-4'-β-D-glucuronide which was purified by semi-preparatory HPLC. The purity of the isolated compound was confirmed by NMR analysis. The identified 5,3',4'-trihydroxy-3-methoxy-6:7-methylen-dioxyflavone-4'-β-D-(2′-O-feurloyl-glucuronide) was the prominent flavonoid and the level was significantly higher in the acetone fraction (2.95 ± 0.16 µg/g FW). This study demonstrates the systematic identification of potential bioactive compounds especially glucuronide derivatives from spinach.

Valorization of Grapefruit Seeds: Cold Press Oil Production

The aims of this study were valorization of grapefruit seeds by producing oil with cold press technique and characterization of the obtained oils. Control group and enzyme treated seeds were cold pressed in laboratory scale machine, and common physicochemical properties, fatty acid, sterol, tocopherol, flavonoid, phenolic acid, pigment, volatile aromatics compositions of the oils were determined in addition to their sensory descriptive analyses. It was shown that the oil contains linoleic acid (40%), β-sitosterol (80%) and α-tocopherol (220–320 mg/kg oil) as the major components. Naringin, hesperidin, neohesperidin, rutin as prominent flavonoids; tr-ferulic and gallic acids as dominant phenolic acids were quantified. Furthermore 26 different (d-limonene, furfural, 3-methylbutanal etc.) volatile aromatics were determined. The oils are shown to be bioactives and aromatics rich samples, but they have strong bitter and astringent taste. Hence, the oil could only be used to enrich other edible oils and foods for functional purposes, and could be utilised for cosmetic, chemical, energy and other purposes.

A comparative metabolomics study of flavonoids in sweet potato with different flesh colors (Ipomoea batatas (L.) Lam)

To study the diversity and cultivar-specific of phytochemicals in sweet potato, Liquid Chromatography-Electrospray Ionization-Mass Spectrometry was used to analyze the metabolic profiles of five sweet potato cultivars exhibiting different flesh colors: purple, yellow/orange, and white. A total of 213 metabolites, including 29 flavonoids and 27 phenolic acids, were characterized. The flavonoid profiles of the five different cultivars were distinguished using PCA, the results suggested the flesh color accounted for the observed metabolic differences. In addition to anthocyanins, quinic acids and ferulic acids were the prominent phenolic acids, O-hexoside of quercetin, chrysoeriol were the prominent flavonoids in sweet potato tubers, and they were all higher in the OFSP and PFSP than WFSP. The main differential metabolic pathways between the OFSP, PFSP and the WFSP included those relating to phenylpropanoid and flavonoid biosynthesis. This study provides new insights into the differences in metabolite profiles among sweet potatoes with different flesh colors.

Chemical and Sensory Properties of Greenhouse Tomatoes Remain Unchanged in Response to Red, Blue, and Far Red Supplemental Light from Light-emitting Diodes

In addition to photosynthesis, light is a critical mediator of secondary metabolism in plants, signaling the production of potentially health-promoting phytochemicals and regulating the emission of volatile organic compounds (VOCs) that can alter the sensory perception of a tomato. Light-emitting diodes (LEDs) are a viable way to test the effects of individual wavebands of light and are being quickly adopted by the greenhouse tomato industry. However, studies characterizing the effects of specific wavelengths of light or supplemental lighting on phytochemical content in general are lacking. We hypothesized that enriching the amount of supplemental blue and/or red light that tomatoes receive would positively affect the amount of carotenoids and phenolic compounds that accumulate in tomato fruits through cryptochrome and/or phytochrome-dependent signaling pathways. To test this hypothesis, we compared the chemical and sensory characteristics of tomatoes grown with overhead high-pressure sodium (OH-HPS) lamps to those grown with intracanopy (IC)-LEDs emitting different ratios of red, blue, and far red light. Tomatoes were profiled for total soluble solids, titratable acidity, ascorbic acid content, pH, total phenolics, and prominent flavonoids and carotenoids. Our studies indicated that greenhouse tomato fruit quality was only marginally affected by supplemental light treatments. Moreover, consumer sensory panel data indicated that tomatoes grown under different lighting treatments were comparable across the lighting treatments tested. Our research suggests that the dynamic light environment inherent to greenhouse production systems may nullify the effects of wavelengths of light used in our studies on specific aspects of fruit secondary metabolism.

Genome-Wide Identification, Localization, and Expression Analysis of Proanthocyanidin-Associated Genes in Brassica.

Proanthocyanidins (PA) is a type of prominent flavonoid compound deposited in seed coats which controls the pigmentation in all Brassica species. Annotation of Brassica juncea genome survey sequences showed 72 PA genes; however, a functional description of these genes, especially how their interactions regulate seed pigmentation, remains elusive. In the present study, we designed 19 primer pairs to screen a bacterial artificial chromosome (BAC) library of B. juncea. A total of 284 BAC clones were identified and sequenced. Alignment of the sequences confirmed that 55 genes were cloned, with every Arabidopsis PA gene having 2–7 homologs in B. juncea. BLAST analysis using the recently released B. rapa or B. napus genome database identified 31 and 58 homologous genes, respectively. Mapping and phylogenetic analysis indicated that 30 B. juncea PA genes are located in the A-genome chromosomes except A04, whereas the remaining 25 genes are mapped to the B-genome chromosomes except B05 and B07. RNA-seq data and Fragments Per Kilobase of a transcript per Million mapped reads (FPKM) analysis showed that most of the PA genes were expressed in the seed coat of B. juncea and B. napus, and that BjuTT3, BjuTT18, BjuANR, BjuTT4-2, BjuTT4-3, BjuTT19-1, and BjuTT19-3 are transcriptionally regulated, and not expressed or downregulated in yellow-seeded testa. Importantly, our study facilitates in better understanding of the molecular mechanism underlying Brassica PA profiles and accumulation, as well as in further characterization of PA genes.

Fast simultaneous determination of prominent polyphenols in vegetables and fruits by reversed phase liquid chromatography using a fused-core column

A reversed-phase high-performance liquid chromatography method with photodiode array detection has been developed enabling the joint determination of 17 prominent flavonoids and phenolic acids in vegetables and fruits. A multi-segmented gradient program using a fused-core column for the separation of several phenolic classes (phenolic acids and flavonoids) has been optimised. The influence of extraction conditions (sample freeze-drying, ultrasound extraction, solvent composition and extraction time) has been also optimised using response surface methodology with tomato samples as a model. Complete recoveries (76–108%) were obtained for the phenolic compounds present in tomato. The developed method provided satisfactory repeatability in terms of peak area (RSD<2.9%) and retention time (RSD<0.2%) both for standards and real samples. Detection limits ranged between 3 and 44μgkg−1 for the detected polyphenols. This method is recommended for routine analysis of large number of samples typical of production quality systems or plant breeding programs.

Phenolic profile and antioxidant activity of various extracts from Citrullus colocynthis (L.) from the Pakistani flora

The aim of the present study was to quantify phenolic acids and flavonoids from Citrullus colocynthis roots (CCR), leaves (CCL) fruits (CCF) and compare the antioxidant and free radical scavenging activities of their extracts and major compounds. Reverse phase high performance liquid chromatography method was developed and validated for the simultaneous quantification of phenolic acids and flavonoids from ethanol and hexane extracts of CCR, CCL and CCF. The antioxidant activity of CCR, CCL and CCF extracts was investigated by measuring total phenolics, total flavonoids contents, DPPH free radical scavenging activity, inhibition of linoleic acid peroxidation and reducing power. The RP-HPLC analysis of C. colocynthis extracts revealed the presence of ferulic acid, vanillic acid, p-coumeric acid, gallic acid, p-hydroxy benzoic acid and chlorogenic acid being the major phenolic acids and quercetin, myricetin and catechin being the most prominent flavonoids compounds. The amounts of TP (3.07–18.6mg/g of dry plant material, measured as gallic acid equivalent) and TF (0.51–13.9mg/g of dry plant material, measured as catechin equivalent) were higher in ethanol extracts of CCL, followed by CCR and CCF. Ethanol extract of CCL exhibited the highest antioxidant and DPPH radical scavenging activities followed by ethanol extracts of CCR and CCF. However, only hexane extract of CCF showed considerable DPPH radical scavenging activity. The results suggested that CCR, CCL and CCF extracts showed a wide variability of their phenolic acids and flavonoids composition and antioxidant activity.

New validated high‐performance liquid chromatographic method for simultaneous analysis of ten flavonoid aglycones in plant extracts using a C18 fused‐core column and acetonitrile–tetrahydrofuran gradient

An HPLC method of high resolution has been developed and validated for the simultaneous determination of ten prominent flavonoid aglycones in plant materials using a fused-core C18-silica column (Ascentis® Express, 4.6 mm × 150 mm, 2.7 μm). The separation was accomplished with an acetonitrile-tetrahydrofuran gradient elution at a flow rate of 1 mL/min and temperature of 30°C. UV spectrophotometric detection was employed at 370 nm for flavonols (quercetin [QU], myricetin [MY], isorhamnetin [IS], kaempferol [KA], sexangularetin [SX], and limocitrin [LM]) and 340 nm for flavones (apigenin [AP], acacetin [AC], chrysoeriol [CH], and luteolin [LU]). The high resolution of critical pairs QU/LU (10.50), QU/CH (3.40), AP/CH (2.51), SX/LM (2.30), and IS/KA (2.70) was achieved within 30.3 min. The observed column back pressure was less than 4300 psi, thus acceptable for conventional HPLC equipment. The method was sensitive enough having LODs of 0.115-0.525 ng and good linearity (r > 0.9999) over the test range. The precision values, expressed as RSD values, were <7.5%, and the accuracy was in the range of 95.3-100.2% for all analytes except MY (73.8%). The method was successfully employed for the determination of flavonoids in several medicinal plants, such as Ginkgo biloba, Betula pendula, and a variety of Sorbus species.

Pre‐clinical evidence of enhanced oral bioavailability of the P‐glycoprotein substrate talinolol in combination with morin

Most known interactions between herbal extracts and drugs involve the inhibition of drug-metabolizing enzymes, but little is yet known about the possible role of transporters in these interactions. In order to evaluate the effect of one of such prominent flavonoids, morin, on P-glycoprotein related efflux carriers, measurements of transport characteristics through Ussing chambers, in situ perfusion and in vivo drug absorption studies were performed with the transported, yet not metabolized model compound talinolol.This study investigated the effects of orally administered morin (1.0, 2.5 and 5.0 mg kg(-1)), on the pharmacokinetics of orally (10 mg kg(-1)) and intravenously (1.0 mg kg(-1)) administered talinolol in rats. In the presence of morin, the pharmacokinetic parameters of talinolol were significantly altered in the oral group but not in the intravenous group. The presence of 2.5 and 5.0 mg kg(-1) of morin significantly increased (1.8-2.0 fold, p<0.01) the area under the plasma concentration-time curve and the peak plasma concentration (2.3-3.0 fold, p<0.01) of orally administered talinolol. The absolute bioavailability (F %) of talinolol in the rats pretreated with morin was significantly higher (89.09-98.29%, p<0.01) than the control (52.14%). Talinolol demonstrated asymmetric transport across rat ileum with significantly greater basolateral-to-apical (B-A) permeability than that in the apical-to-basolateral (A-B) direction. The addition of morin resulted in a concentration dependent effect, especially on the secretory transport of talinolol.The present study demonstrates that morin bears the ability to interfere with secretory intestinal transport processes. This might be due to an interaction with P-glycoprotein.

Antioxidant Effects of Xanthohumol and Functional Impact on Hepatic Ischemia−Reperfusion Injury

Therapeutic effects of dietary flavonoids have been attributed mainly to their antioxidant capacity. Xanthohumol (1), a prominent flavonoid of the hop plant, Humulus lupulus, was investigated for its antioxidant potential and for its effect on NF-kappaB activation. To examine the biological relevance of 1, a hepatic ischemia/reperfusion model was chosen as a widely accepted model of oxidative stress generation. The impact of 1 on endogenous antioxidant systems, on the NF-kappaB signal transduction pathway as well as on apoptotic parameters, and on hepatic tissue damage was evaluated. Compound 1 markedly decreased the level of reactive oxygen species in vitro. Furthermore, levels of enzymatic and nonenzymatic antioxidants were restored after pretreatment in postischemic hepatic tissue, and lipid peroxidation was attenuated. NF-kappaB activity was reduced in vitro as well as in hepatic tissue after ischemia/reperfusion upon pretreatment with 1. In addition, the phosphorylation of Akt was markedly inhibited. Surprisingly, 1 decreased the expression of the antiapoptotic protein Bcl-X and increased caspase-3 like-activity, a proapoptotic parameter. Moreover, hepatic tissue damage as well as TNF-alpha levels increased in xanthohumol-pretreated liver tissue after ischemia/reperfusion. In summary, xanthohumol did not protect against ischemia/reperfusion injury in rat liver, despite its antioxidant and NF-kappaB inhibitory properties.