Dietary flavonoids and human top-ranked diseases: The perspective of in vivo bioactivity and bioavailability

Author(s):  
Di Zhou ◽  
Zisong Bai ◽  
Tingting Guo ◽  
Jiayi Li ◽  
Yanwu Li ◽  
...  
Keyword(s):  
2002 ◽  
Vol 40 (3) ◽  
pp. 243-248 ◽  
Author(s):  
Rainer Simmering ◽  
Holger Pforte ◽  
Gisela Jacobasch ◽  
Michael Blaut

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 327-327
Author(s):  
Jessica Kim ◽  
Meenakshi Sudhakaran ◽  
Elahé Crockett ◽  
Andrea Doseff

Abstract Objectives Breast cancer remains the leading cause of malignancy-related death in females and continues to increase in prevalence worldwide. The lack of therapies for triple-negative breast cancer (TNBC) continues to be a challenge, owing to its highly metastatic and aggressive nature. Dietary flavonoids, found in fruits and vegetables, are attracting great interest in the prevention and treatment of TNBC due to their anti-carcinogenic, anti-oxidative, and anti-inflammatory properties. The goal of our project was to evaluate the structure-activity relationship and the mechanism by which flavonoids affect TNBC tumor growth and metastasis. Methods We investigated the effects of structurally related flavonoids on the migratory nature of human MDA-MB 231 TNBC cells by using a wound healing migration assay. To model the effects of flavonoids in tumor heterogeneity in vivo, 3-dimensional culture organoids from TNBC derived xenograft tumors were established. Small interfering RNA (siRNA) transfection of apigenin target heterogeneous nuclear ribonucleoproteins A2 (hnRNPA2), an oncogene overexpressed in cancer cells that leads to abnormal mRNA splicing, were employed to investigate how hnRNPA2 effects alternative mRNA splicing activity. Results We observed that the natural flavonoids apigenin and kaempferol inhibited migration in a dose-response manner. Conversely, the presence of a glucoside and/or the lack of double bonds within the flavonoid structure as in the case of apigenin-7-glucoside and flavanones exhibited no significant anti-metastatic effects. Analysis of hnRNPA2 knockdown revealed key insights into the interaction of apigenin with hnRNPA2 to regulate migratory behaviors. Conclusions These novel insights showcase dietary flavonoids as practical functional foods that can benefit clinical applications in TNBC cancer prevention and treatment of tumor metastases and growth. Funding Sources Through grants from United States Department of Agriculture, National Science Foundation, and MSU awarded to Dr. Andrea I. Doseff, NIH-T32 Plant Biotechnology for Health and Sustainability Fellowship to Meenakshi Sudhakaran, and the REPID Program funded by National Institute of Health and directed by Dr.  Elahé Crockett.


Mutagenesis ◽  
1989 ◽  
Vol 4 (5) ◽  
pp. 365-370 ◽  
Author(s):  
A.J. Alldrick ◽  
B.G. Lake ◽  
I.R. Rowland

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6289
Author(s):  
Sinenhlanhla X. H. Mthembu ◽  
Christo J. F. Muller ◽  
Phiwayinkosi V. Dludla ◽  
Evelyn Madoroba ◽  
Abidemi P. Kappo ◽  
...  

The current study investigated the physiological effects of flavonoids found in daily consumed rooibos tea, aspalathin, isoorientin, and orientin on improving processes involved in mitochondrial function in C2C12 myotubes. To achieve this, C2C12 myotubes were exposed to a mitochondrial channel blocker, antimycin A (6.25 µM), for 12 h to induce mitochondrial dysfunction. Thereafter, cells were treated with aspalathin, isoorientin, and orientin (10 µM) for 4 h, while metformin (1 µM) and insulin (1 µM) were used as comparators. Relevant bioassays and real-time PCR were conducted to assess the impact of treatment compounds on some markers of mitochondrial function. Our results showed that antimycin A induced alterations in the mitochondrial respiration process and mRNA levels of genes involved in energy production. In fact, aspalathin, isoorientin, and orientin reversed such effects leading to the reduced production of intracellular reactive oxygen species. These flavonoids further enhanced the expression of genes involved in mitochondrial function, such as Ucp 2, Complex 1/3, Sirt 1, Nrf 1, and Tfam. Overall, the current study showed that dietary flavonoids, aspalathin, isoorientin, and orientin, have the potential to be as effective as established pharmacological drugs such as metformin and insulin in protecting against mitochondrial dysfunction in a preclinical setting; however, such information should be confirmed in well-established in vivo disease models.


2003 ◽  
Vol 73 (2) ◽  
pp. 101-111 ◽  
Author(s):  
Rasmussen ◽  
Breinholt

Flavonoids are polyphenols widely distributed in the plant kingdom, and are present in fruits andvegetables regularly consumed by humans. In vitro metabolic studies of flavonoids in rat liver microsomes identified the 3’, 4’-dihydroxylated derivatives as the major metabolic endpoint. However, in vivo in rats almost none of this metabolite and only minor amounts of the 4’-monohydroxylated derivative was produced. Flavonoids with the 4’-monohydroxylated structure were generally not metabolised and were excreted unchanged in urine in higher amounts than other flavonoids investigated. It has for long been a controversy, whether flavonoids are absorbed as the intact glycoside or whether they have to be hydrolysed to the free aglycon prior to absorption. Recent data suggest that b-glucosidases and maybe also lactase phlorizin hydrolase (LPH) in the small intestine are capable of hydrolysing flavonoid glucosides and these compounds are thus taken up as the free aglycon and not as the intact glycosides. LC-MS analyses of 12 dietary flavonoids in human urine showed that no flavonoid glycosides were excreted, and that the citrus flavanones and phloretin are excreted in higher amounts than the flavonols. Furthermore, total flavonoid excretion may be a useful biomarker for habitual fruit and vegetable consumption.


2003 ◽  
Vol 34 (7) ◽  
pp. 795-799 ◽  
Author(s):  
Joye K Willcox ◽  
George L Catignani ◽  
L.Jackson Roberts
Keyword(s):  

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P180-P180 ◽  
Author(s):  
William B Helton ◽  
Eun-Young Choi ◽  
C Gary Gairola ◽  
Joseph Valentino ◽  
Swanson Hollie

Problem Dietary flavonoids are being investigated as chemopreventative agents for many cancers. The objective of this study was to determine whether the dietary flavonoids apigenin and kaempferol inhibit growth of malignant oral keratinocytes. Methods FaDu cells were treated with increasing concentrations of apigenin and kaempferol. After 24 and 48 hours cell growth was determined using the WST-1 assay. Three groups of nude mice (group 1-kaempferol, group 2-apigenin, group 3-controls) were treated by gavage for one week prior to inoculation with FaDu cells (1 × 105 cells) Following inoculation, treatments were continued until sacrifice. Tumor volumes were calculated from three dimensional tumor measurements. Results In vitro cell growth decreased with increasing concentrations of apigenin and kaempferol (p<0.001). In vivo tumor volume was significantly higher than controls for the apigenin group (p<0.03) but was marginally higher in kaempferol group (p=0.09) with an average volume of 3024mm3, 2610 mm3, and 1858 mm3 respectively. Conclusion Apigenin and kaempferol inhibited tumor cell growth in culture. However, in vivo results show that these substances increased tumor burden. This is in contrast to previous in vivo and in vitro prostate cell line models showing apigenin inhibition of tumor growth. Further studies are needed to better evaluate the effect these dietary flavonoids exert on squamous cell carcinoma of the head and neck. Significance The role of these agents as chemopreventative agents for oral carcinoma is not supported by our data. Support University of Kentucky Department of Surgery Research Grant and NIH R-01 grant.


2005 ◽  
Vol 94 (3) ◽  
pp. 338-345 ◽  
Author(s):  
Mara Fiorani ◽  
Augusto Accorsi

The plasma membrane oxidoreductase (PMOR) activity, which mainly utilises ascorbate as intracellular electron donor, represents a major mechanism for cell-dependent reduction of extracellular oxidants and might be an important process used by the erythrocytes to keep a reduced plasma environment. We previously reported that in human erythrocytes, myricetin and quercetin act as intracellular substrates of a PMOR showing a novel mechanism whereby these flavonoids could exert beneficial effects under oxidative stress conditions. Here, we evaluated the ability of different flavonoids (quercetin, myricetin, morin, kaempferol, fisetin, catechin, luteolin, apigenin, acacetin, rutin, taxifolin, naringenin, genistein) and of two in vivoO-methylated metabolites of quercetin (isorhamnetin and tamarixetin) to be substrates of PMOR, by comparing their antioxidant capacity (i.e. direct interaction with the oxidant ferricyanide or with the free radical 1,1-diphenyl-2-picryl-hydrazil) with their ability to penetrate the erythrocytes and donate electrons to the PMOR. The results obtained indicate that, although most of the flavonoids display significant antioxidant activities, only those (quercetin, myricetin, fisetin) that combine the cathecol structure of the B ring (responsible for the reducing activity) with the 2,3 double bond and 4-oxo function of the C ring (responsible for the uptake by erythrocytes) can act as intracellular substrates for PMOR. It is of note that the metabolites of quercetin enter erythrocytes and donate electrons to the PMOR as the parent compound. The present data show a relationship between the flavonoid structures and their ability to provide electrons to the PMOR, suggesting an additional mechanism whereby dietary flavonoids may exert beneficial effects in man.


Antioxidants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 202 ◽  
Author(s):  
Jennifer Ahn-Jarvis ◽  
Arti Parihar ◽  
Andrea Doseff

Flavonoids, one of the most abundant phytochemicals in a diet rich in fruits and vegetables, have been recognized as possessing anti-proliferative, antioxidant, anti-inflammatory, and estrogenic activities. Numerous cellular and animal-based studies show that flavonoids can function as antioxidants by preventing DNA damage and scavenging reactive oxygen radicals, inhibiting formation of DNA adducts, enhancing DNA repair, interfering with chemical damage by induction of Phase II enzymes, and modifying signaling pathways. Recent evidence also shows their ability to regulate the immune system. However, findings from clinical trials have been mixed with no clear consensus on dose, frequency, or type of flavonoids best suited to elicit many of the beneficial effects. Delivery of these bioactive compounds to their biological targets through “targeted designed” food processing strategies is critical to reach effective concentration in vivo. Thus, the identification of novel approaches that optimize flavonoid bioavailability is essential for their successful clinical application. In this review, we discuss the relevance of increasing flavonoid bioavailability, by agricultural engineering and “targeted food design” in the context of the immune system and cancer.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Eduardo Scandinari Manzolli ◽  
Juliana Mara Serpeloni ◽  
Denise Grotto ◽  
Jairo Kennup Bastos ◽  
Lusânia Maria Greggi Antunes ◽  
...  

The use of phytochemicals has been widely used as inexpensive approach for prevention of diseases related to oxidative damage due to its antioxidant properties. One of dietary flavonoids is chrysin (CR), found mainly in passion fruit, honey, and propolis. Methylmercury (MeHg) is a toxic metal whose main toxic mechanism is oxidative damage. Thus, the study aimed to evaluate the antioxidant effects of CR against oxidative damage induced by MeHg in Wistar rats. Animals were treated with MeHg (30 µg/kg/bw) in presence and absence of CR (0.10, 1.0, and 10 mg/kg/bw) by gavage for 45 days. Glutathione (GSH) in blood was quantified spectrophotometrically and for monitoring of DNA damage, comet assay was used in leukocytes and hepatocytes. MeHg led to a significant increase in the formation of comets; when the animals were exposed to the metal in the presence of CR, higher concentrations of CR showed protective effects. Moreover, exposure to MeHg decreased the levels of GSH and GSH levels were restored in the animals that received CR plus MeHg. Taken together the findings of the present work indicate that consumption of flavonoids such as CR may protect humans against the adverse health effects caused by MeHg.


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