¿What are flavonoids and why should you care?
Flavonoids are natural products commonly found in vegetables, fruits, plants, bark, flowers, wine and tea such as Palo Azul.
These are some of the MOST flavonoid-rich foods: apples, pears, onions, strawberries, blueberries, celery, peppers, and teas such as palo azul
What makes them so special?
There are literally HUNDREDS of studies that have found numerous health benefits in flavonoids and these are are attributed to their anti-oxidative, anti-inflammatory, anti-diabetic, anti-aging, anti-hypertensive, anti-bacterial, anti-mutagenic, anti-viral and anti-carcinogenic properties.
For example, numerous epidemiological (population) studies show an “inverse correlation between dietary flavonoid consumption and chronic degenerative diseases, such as cardiovascular diseases, diabetes, osteoporosis, neurodegenerative diseases, and cancers.”
According to a medical review, flavonoids’ powerful health benefits have made them “an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications.”
Here we’ve summarized the most important health benefits we found:
1.) They lower cholesterol and blood pressure
2.) They help you burn abdominal fat
3.) Protect against aging and wrinkles
4.) Reduce your risk of cardiovascular disease, cancer, diabetes, atherosclerosis, hypertension, erectile dysfunction, arthritis, Alzheimer's and Parkinson's disease, and dementia
5.) They are antibacterial, antiviral and protect against E.coli
We know….this might be the healthiest compound on planet Earth!
This is why we should be eating vegetables, fruits and drinking palo azul tea (or wine occasionally) everyday!
How can flavonoids help you?
Lower your cholesterol
One study done on flavonoids concluded that “flavonoids in tea may lower blood cholesterol concentrations and blood pressure, thereby providing some protection against cardiovascular disease.”
Another study found that the antioxidant property of flavonoids " inhibits the oxidation of LDL cholesterol.”
Finally, another study concluded that: “Palo Azul (EP) reduced the blood glucose, increased serum insulin, body weight, marker enzymes of hepatic function, glycogen, HDL, GK and HK while there was reduction in the levels of triglyceride, cholesterol.”
You can read the full article here: Palo Azul vs. Cholesterol
They help you lose weight
One study analyzed 2754 twins and found that the group that consumed the most flavonoids:
- Had less percentage of fat
- Burned more fat in the abdomen
Specifically, the researchers found that the twins with the highest consumption of flavonoid-rich foods (onions, tea, apples, pears, and cocoa) “had a 3-9% lower FMR (fat mass ratio) than that of their co-twins.”
Moreover, the researchers found that the “women who ate a lot of flavonoid-rich foods had a lower percentage of body fat than women who ate less. The amount of abdominal fat also differed significantly between the two groups.”
The researchers of this study also point out that “It is important to note that abdominal fat is an important risk factor for diseases such as type 2 diabetes and heart problems.”
Another study looked at 124,000 people and found that "flavonoids increase energy expenditure, decrease fat absorption and function as anti-inflammatories. The researchers in this same study found that "increased consumption of most flavonoid subclasses was associated with reduced weight gain.”
They also mentioned that the participants that consumed more flavonoids maintained their weight better and even lost some weight and they concluded the following:
"Our results suggest that choosing fruits and vegetables that are high in flavonoids, such as apples, pears, berries and peppers, can help with weight control."
You can read the full article here: Palo Azul for Weight Loss
They protect against wrinkles
Victoria Lewis, a doctor of dermatology mentions that “antioxidants are often considered the fountain of youth by skin-care professionals and experts.”
“Not only do they (antioxidants) scavenge free radicals—the number one skin-aging culprits—to promote a brighter, more even complexion, they’re also the superstars at nixing fine lines and keeping skin looking fresh.”
This is due to its ability to eliminate oxidative stress and free radicals, which are “the number one skin-aging culprits.”
This oxidative stress causes damage to our cells, and this damage eventually leads to aging and wrinkles in our skin.
Another doctor of dermatology, Dr. Mack, writes that “antioxidants protect your skin from this (oxidative stress) and help reduce pigmentation and fine lines and wrinkles.” He goes on to mention that in his opinion, “an antioxidant serum is a must for your skin-care routine.”
For this reason, many pharmaceutical and cosmetic companies supplement their skin care products with tea extracts!
You can read the full article here: Palo Azul vs Aging and Wrinkles
Reduce your risk of cancer
We read two medical reviews composed of findings from 327 studies done specifically on flavonoids, and found that oxidative stress can lead to cancer, diabetes, cardiovascular disease, and aging ... For this reason, they found that antioxidants show potential to fight these diseases.
Therefore, diets rich in antioxidants decrease the cancer-promoting action of free radicals and oxidative stress. One of the studies we reviewed found that fruits and vegetables that have flavonoids have been reported as cancer chemopreventive agents and are inversely associated with cancer incidence.
*Here’s a very interesting fact for wine drinkers: “Moderate wine drinkers also seem to have a lower risk to develop cancer of the lung, endometrium, esophagus, stomach, and colon.”
Thank you flavonoids!
We also read a study that recruited 1522 breast cancer cases and 1547 frequency control subjects from June 2007 to July 2018 in Guangdong, China. The results of this study indicated that consumption of “flavonoids and most flavonoid subclasses intakes were inversely associated with breast cancer risk.”
You can read the full article here: Palo Azul vs. Cancer
Finally, “the critical relationship of fruit and vegetable intake and cancer prevention has been thoroughly documented. It has been suggested that major public health benefits could be achieved by substantially increasing consumption of these foods.”
In other words... oxidation in our body leads to cancer and other diseases, therefore we should consume lots of antioxidants to stay healthy.
Reduce risk of diabetes
Numerous epidemiological studies show an “inverse correlation between dietary flavonoid consumption and chronic degenerative diseases, such as cardiovascular diseases, diabetes, osteoporosis, neurodegenerative diseases, and cancers.”
One study concludes the following: “Oxidative stress may lead to cellular damage which is related to various health ailments such as diabetes, cancer, CVD, neurodegenerative disorders and ageing. Antioxidants interfere with radical-producing systems and increase the function of endogenous antioxidants, protecting the cells from damage by these free radicals.”
Another study mentions that “flavonoids have a role in the treatment of diabetes by virtue of their ability to protect against hyperglycemic and alloxan-induced oxidative stress in experimental animal models.”
Lastly, in a large cohort of women, a clinical trial has shown that "flavonoids are protective against type 2 diabetes.”
You can read the full article here: Palo Azul vs. Diabetes
Reduce risk of cardiovascular disease
Epidemiological, clinical and animal studies reveal that “flavonoids may exert protective effects against various disease conditions including cardiovascular disease and cancer.”
Other population studies have demonstrated that “flavonoid intake is inversely correlated with mortality from cardiovascular disease.”
Researchers also found that flavonoids may “lower blood cholesterol concentrations and blood pressure, thereby providing some protection against cardiovascular disease.”
Finally, a study concluded the following:
"Antioxidant, antithrombotic, anti-inflammatory, and hypolipidemic properties play a significant role in the lower cardiovascular mortality illustrated by increased flavonoid consumption.”
Reduce risk of atherosclerosis
Various epidemiological studies show that “flavonoids in tea may lower blood cholesterol concentrations and blood pressure, thereby providing some protection against cardiovascular disease.”
This is due to its ability to "inhibit the oxidation of LDL through a mechanism involving the elimination of free radicals that plays a key role during atherosclerosis.”
One study established the importance of the oxidation of LDL cholesterol by writing that “oxidative modification of LDL cholesterol is thought to play a key role during atherosclerosis.”
Reduce your risk of Hypertension
We’ve read two medical reviews composed of findings from 327 different studies conducted specifically on flavonoids, and their findings revealed that "dietary flavonoids are associated with a lower risk of hypertension and CVD (cardiovascular disease).”
The scientists who published these reviews also observed that “the blood pressure level was reduced in patients with hypertension” after greater consumption of flavonoids.
Finally, one study concluded the following:
“Flavonoids in tea may lower blood cholesterol concentrations and blood pressure, thereby providing some protection against cardiovascular disease.”
Reduce your risk of Alzheimer, Parkinson, or Dementia
A very interesting study analyzed a group of 49,281 men and 80,336 women in the Health Professionals Follow-up Study and found that “the participants in the highest quintile of total flavonoids had a 40% lower PD (Parkinson’s Disease) risk than those in the lowest quintile.” The researchers from this study concluded the following:
“Our findings suggest that intake of some flavonoids may reduce PD (Parkinson's Disease) risk”
Another study found that flavonoids have “favourable biochemical and antioxidant effects associated with various diseases such as cancer, Alzheimer's disease (AD), atherosclerosis, etc.”
FInally, a study concluded the following:
“Flavonoids contained in berries may have a positive effect against Parkinson's disease and may help to improve memory in elderly people. Intake of antioxidant flavonoids has been inversely related to the risk of incidence of dementia.”
Reduce risk of erectile dysfunction
Results from one study "showed that “flavonoid consumption 50 mg/day reduced the risk of erectile dysfunction by 32%.”
Another study found similarly that "flavonoid-rich foods are associated with a reduced incidence of erectile dysfunction.”
Additionally, one study found that "men with erectile dysfunction reported a lower monthly average of total flavonoid intake."
Due to the antioxidant capacity of flavonoids, another study concludes that flavonoids "may ameliorate erectile dysfunction by inhibiting oxidative stress."
Finally we’re done with flavonoids and antioxidants! But there’s still much left to cover :)
You can read the full article here: Palo Azul vs Erectile Dysfunction
Protect against bacteria and E.coli
A medical review that analyzed the results of 161 studies mentioned that flavonoids proved to be potent antimicrobial and viral inhibitors.
Therefore, they are found to be effective against many infectious diseases (bacterial and viral) such as E. coli.
* Here is an interesting finding!
“Flavonoids are known to be synthesized by plants in response to microbial infection; thus it should not be surprising that they have been found in vitro to be effective antimicrobial substances against a wide array of microorganisms.” It’s due to their potent antibacterial, antimicrobial and antiviral activity that flavonoids “show inhibitory activity against E. coli."
“Flavonoids have also been recognised for their antimicrobial activity and many researchers have isolated and identified the structures of flavonoids having properties of antifungal, antiviral and antibacterial activity. Because of this property, many flavonoids are now being used extensively in the fields of nutrition, food safety and health.”
You can read our full article here: Palo Azul vs. Bacteria
Protect against viruses
Another medical review which reviewed 166 studies mentions the following about flavonoids:
"It is due to their potent antibacterial, antimicrobial and antiviral activity that flavonoids show inhibitory activity against E. coli."
This same medical review also found that “many flavonoids show activity against several types of virus including HSV, respiratory syncytial virus, polio virus and Sindbis virus [135].”
* Here is an interesting finding!
One study mentioned that flavonoids “are an important source for the discovery and the development of novel antiviral drugs.”
What types of viruses can flavonoids block?
Recently, we found a study published in 2020 which found that “flavonoids block attachment and entry of viruses into cells, interfere with various stages of viral replication processes or translation and polyprotein processing to prevent the release of the viruses to infect other cells.”
The researchers mention that “flavonoids are natural biomolecules that are known to be effective antivirals” and that “these biomolecules can act at different stages of viral infection, particularly at the molecular level to inhibit viral growth.”
* What's really interesting though, is that they found that flavovonoids have inhibitory effects against Ebola, herpes, HIV, Influenza and coronaviruses!
Lastly, the researchers mention that due to flavonoids’ ability to target various stages of viral infection, they are “becoming a more focused topic to explore their potential as antivirals in the current era.”
For all these reasons, flavonoids are used to develop new antiviral drugs.
You can read the full article here: Palo Azul vs. Virus
Reduce joint pain
One study found a very surprising fact: “study found that flavonoids (found in vegetables, fruits and teas like palo azul) “have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D.”
This finding is supported by population studies which have shown “flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption.”
You can read the entire article here: Palo Azul can Strengthen your Joints!
Alleviate abdominal pain, nausea, digestive issues and loss of appetite
A medical review showed the efficacy of flavonoids “in the treatment of hepatobiliary dysfunction and digestive complaints, such as sensation of fullness, loss of appetite, nausea, and abdominal pain.”
Loss of appetite is also commonly attributed to bacteria and viruses, and many studies have demonstrated the potent antibacterial and antiviral activity of Palo Azul and its flavonoids.
Medical Studies
* Palo Azul is commonly referred to by its scientific name: Eysenhardtia polystachya / E. polystachya / E.P - Cyclolepis genistoides / C. genistoides - kidney wood - palo dulce
(2012) Flavonoid intake and bone health
Flavonoids, found in a wide diversity of plant foods from fruits and vegetables, herbs and spices, essential oils, and beverages, have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D. Recent epidemiological studies show flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption. Bioactive flavonoids are being assessed for properties beyond their chemical antioxidant capacity, including anti-inflammatory actions. Some have been reported to enhance bone formation and to inhibit bone resorption through their action on cell signaling pathways that influence osteoblast and osteoclast differentiation.
Flavonoids, found in a wide diversity of plant foods from fruits and vegetables, herbs and spices, essential oils, and beverages, have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D. Recent epidemiological studies show flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption. Bioactive flavonoids are being assessed for properties beyond their chemical antioxidant capacity, including anti-inflammatory actions. Some have been reported to enhance bone formation and to inhibit bone resorption through their action on cell signaling pathways that influence osteoblast and osteoclast differentiation.
(2009) Chapter 18 - Flavonoids and Cardiovascular Health
More than 8000 compounds with flavonoids structure have been identified, many of which are responsible for the attractive colors of flowers, fruits and leaves. In plants, these compounds afford protection against ultraviolet radiation, pathogens, and herbivores [1, 2].
Studies have indicated the protective effects of flavonoids in cardiovascular diseases and these chemicals possess the bioactivity to positively affect against cardiovascular risk factors such as lipoprotein oxidation, dyslipidemia and endothelial dysfunction. Flavonoids have strong antioxidant properties and so can reduce oxidative stress related to cardiovascular disease. The cardioprotective role of tea is reported to be due to antioxidant effect of the flavonoids, which act as scavengers for free radicals.
Epidemiological, clinical and animal studies reveal that flavonoids may exert protective effects against various disease conditions including cardiovascular disease and cancer. Flavonoids also possess antibacterial, antiviral, and anti-inflammatory effects. Population studies have shown that flavonoid intake is inversely correlated with mortality from cardiovascular disease [3–6]. Flavonoids have been reported to beneficially impact parameters associated with atherosclerosis, including lipoprotein oxidation, blood platelet aggregation, and vascular reactivity. Antioxidant, antithrombotic, anti-inflammatory, and hypolipidemic properties are illustrated to play a significant role in the lower cardiovascular mortality observed with higher flavonoid intake [4, 5, 7]. Continued studies of the mechanisms underlying the biological effects of plant flavonoids may provide new strategies for the prevention and treatment of cardiovascular disease.
(2016, Dec 29) (Medical Review: 161 studies) Flavonoids: an overview
Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD.
The recent studies on different plant metabolites have shown that flavonoids may perform a key role in enzyme and receptor systems of the brain, exerting significant effects on the central nervous system, like prevention of the neurodegeneration associated with AD and Parkinson's disease(,15,119).
They have miscellaneous favourable biochemical and antioxidant effects associated with various diseases such as cancer, Alzheimer's disease (AD), atherosclerosis, etc. Flavonoids have several subgroups, which include chalcones, flavones, flavonols and isoflavones. These subgroups have unique major sources. For example, onions and tea are major dietary sources of flavonols and flavones. A number of flavonoids were studied to lower Alzheimer's Aβ production using molecular docking studies.
Lee et al.(,81), while working on the known flavonoid inhibitors of β-KAS III against the methicillin-resistant bacteria Staphylococcus aureus, found that flavonoids such as naringenin (5,7,4′-trihydroxyflavanone) and eriodictyol (5,7,3′,4′-tetrahydroxyflavanone) are potent antimicrobial inhibitors of Staphylococcus aureus KAS III. Ganugapati et al.(,82) worked on in silico modelling and docking studies of a superbug enzyme, namely New Delhi metallo-β-lactamase-1 (NDM-1), which is an enzyme found in Escherichia coli.
Lu & Chong(,85) carried out the computational work to predict the binding modes of flavonoid derivatives with the neuraminidase of the 2009 haemagglutinin 1 neuraminidase (H1N1) influenza virus. They employed molecular dynamics simulation techniques to optimise the 2009 H1N1 influenza neuraminidase X-ray crystal structure. All the twenty flavonoid derivatives were found to be satisfactory in binding and inhibiting the activity of the virus. These findings may help to develop a potential drug form of the flavonoid derivatives for the treatment of H1N1 influenza disease.
Kim et al.(,87) reported that a flavonoid-rich diet is associated with a reduced risk of CVD (cardiovascular disease). The study focused on individual as well as total flavonoid diet effects. Higher flavonoid intake was found to be associated with the improved CVD risk factors.
The observational studies done by Hügel et al.(,89) indicated that dietary flavonoids are associated with a decreased risk of hypertension and CVD. A diet rich in all flavonoid classes through herbs and beverages improves vascular health leading to a reduced risk of diseases. It has been observed that the consumption of them is associated with improvement in endothelial function via vascular endothelial nitric oxide synthase and protein kinase B (Akt) activation. The effect of regular quercitin intake on blood pressure in overweight and obese patients with pre-hypertension and stage I hypertension was studied in seventy patients. Ambulatory blood pressure and office blood pressure were measured. It was observed that the blood pressure level was reduced in patients with hypertension(,90).
Paris et al.(,97) worked on flavonoids which lower Alzheimer's amyloid protein (Aβ) production via a nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-dependent mechanism. It is well known that AD is due to the accumulation of Aβ peptides and the presence of neurofibrillary tangles in the brain(,98,99). Aβ is believed to play an important role in AD and it has been shown that certain flavonoids such as genistein, quercetin, taxifolin, kaemferol, luteolin, apigenin, daidzein, aminogeneistein, and α- and β-napthofalvone can affect Aβ production. Recently, it was suggested that the Aβ-lowering properties of flavonoids are mediated by a direct inhibition of β active site cleavage enzyme-1 (BACE-1) activity, the rate-limiting enzyme responsible for the production of Aβ peptides(,97). It has been reported that a strong correlation exists between the inhibition of NF-κB activation by flavonoids and their Aβ-lowering properties, suggesting that flavonoids inhibit Aβ production in whole cells via NF-κB-related mechanisms.
Flavonoids can prevent injury caused by free radicals in various ways and one way is the direct scavenging of free radicals. Flavonoids are oxidised by radicals, resulting in a more stable, less-reactive radical. In other words, flavonoids stabilise the reactive oxygen species by reacting with the reactive compound of the radical. Because of the high reactivity of the hydroxyl group of the flavonoids, radicals are made inactive, as explained in the following equation as given by Korkina & Afanasev(,108): They further mentioned that this action protects the LDL particles and, theoretically, flavonoids may have preventive action against atherosclerosis.
Antioxidants are compounds that protect the cells against the oxidative effect of reactive oxygen species, and the impaired balance between these reactive oxygen species and antioxidants results in oxidative stress. The oxidative stress may lead to cellular damage which is related to various health ailments such as diabetes, cancer, CVD, neurodegenerative disorders and ageing. Oxidative stress can also damage many biological molecules and proteins and DNA molecules are significant targets of cellular injury. Antioxidants interfere with radical-producing systems and increase the function of endogenous antioxidants, protecting the cells from damage by these free radicals
Anticancer effects of flavonoids such as tangeritin, 3-hydroxyflavone, 3′,4′-dihydroxyflavone, 2′,3′-dihydroxyflavone, fisetin, apigenin, luteolin daidzein and genistein have been carried out by a number of researchers(,151–154). Ren et al.(,130) and Huang et al.(,155), while working on natural phenolic compounds and their potential use for cancer prevention, reported that various flavonoids such as tannins, stilbenes, curcuminoids, coumarins, lignans, quinones and other flavonoids have chemopreventive properties and also contribute to induce apoptosis by arresting the cell cycle, regulating carcinogen metabolism and ontogenesis expression. While explaining the possible mechanism of flavonoids in cancer prevention they further mentioned that the flavonoids have complementary and overlapping mechanisms of action including antioxidant activity and scavenging free radicals, modulation of carcinogen metabolism, regulation of gene expression on oncogenes and tumour-suppressor genes in cell proliferation and differentiation, induction of cell cycle arrest and apoptosis, modulation of enzyme activities in detoxification, oxidation and reduction, anti-inflammatory properties and action on other possible targets.
Flavonoids have also been recognised for their antimicrobial activity and many researchers have isolated and identified the structures of flavonoids having properties of antifungal, antiviral and antibacterial activity. Because of this property, many flavonoids are now being used extensively in the fields of nutrition, food safety and health. The antiviral effect of flavonoids has been shown by Wang et al.(,142), particularly in therapy for viral infection.
Flavonoids, like flavonols, are associated with lower population rates of dementia(,156). Similarly, Hwang & Yen(,157) and Jager & Saaby(,119) suggested that citrus flavanones such as hesperidin, hesperetin and naringenin could traverse the blood–brain barrier and may play an effective role in the intervention for neurodegenerative diseases. The role of flavonoids in antidiabetic activity and anti-ageing has also been reported(,158–161).
Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine.
Many flavonoids are shown to have antioxidative activity, free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, and anticancer activities, while some flavonoids exhibit potential antiviral activities. In plant systems, flavonoids help in combating oxidative stress and act as growth regulators.
The number of studies has suggested protective effects of flavonoids against many infectious (bacterial and viral diseases) and degenerative diseases such as cardiovascular diseases, cancers, and other age-related diseases. Flavonoids also act as a secondary antioxidant defense system in plant tissues exposed to different abiotic and biotic stresses.
Flavonoids found in the highest amounts in the human diet include the soy isoflavones, flavonols, and the flavones.
Oxidative modification of LDL cholesterol is thought to play a key role during atherosclerosis. The isoflavan glabridin, a major polyphenolic compound found in Glycyrrhiza glabra (Fabaceae), inhibits LDL oxidation via a mechanism involving scavenging of free radicals [52]. Several epidemiological studies have suggested that drinking either green or black tea may lower blood cholesterol concentrations and blood pressure, thereby providing some protection against cardiovascular disease. Flavonoids contained in berries may have a positive effect against Parkinson's disease and may help to improve memory in elderly people. Antihypertensive effect has been observed in total flavonoid fraction of Astragalus complanatus in hypertensive rats [55]. Intake of antioxidant flavonoids has been inversely related to the risk of incidence of dementia.
Flavonoids possess many biochemical properties, but the best described property of almost every group of flavonoids is their capacity to act as antioxidants. The antioxidant activity of flavonoids depends upon the arrangement of functional groups about the nuclear structure. The configuration, substitution, and total number of hydroxyl groups substantially influence several mechanisms of antioxidant activity such as radical scavenging and metal ion chelation ability
Hepatoprotective activities were observed in flavonoids isolated from Laggera alata against carbon-tetrachloride (CCl4-) induced injury in primary cultured neonatal rat hepatocytes and in rats with hepatic damage. Several clinical investigations have shown the efficacy and safety of flavonoids in the treatment of hepatobiliary dysfunction and digestive complaints, such as sensation of fullness, loss of appetite, nausea, and abdominal pain.
Flavonoids are known to be synthesized by plants in response to microbial infection; thus it should not be surprising that they have been found in vitro to be effective antimicrobial substances against a wide array of microorganisms. Flavonoid rich plant extracts from different species have been reported to possess antibacterial activity [70, 72, 89, 90]. Several flavonoids including apigenin, galangin, flavone and flavonol glycosides, isoflavones, flavanones, and chalcones have been shown to possess potent antibacterial activity [91]. These compounds are reported for their in vitro antibacterial activity against Vibrio cholerae, Streptococcus mutans, Shigella, and other bacteria [94, 95]. Another study demonstrated inhibitory activity of quercetin, apigenin, and 3,6,7,3′,4′-pentahydroxyflavone against Escherichia coli DNA gyrase [98].
Inflammation is a normal biological process in response to tissue injury, microbial pathogen infection, and chemical irritation. Inflammation is initiated by migration of immune cells from blood vessels and release of mediators at the site of damage. This process is followed by recruitment of inflammatory cells, release of ROS, RNS, and proinflammatory cytokines to eliminate foreign pathogens, and repairing injured tissues. In general, normal inflammation is rapid and self-limiting, but aberrant resolution and prolonged inflammation cause various chronic disorders [106]. A number of flavonoids such as hesperidin, apigenin, luteolin, and quercetin are reported to possess anti-inflammatory and analgesic effects. It has been reported that flavonoids are able to inhibit expression of isoforms of inducible nitric oxide synthase, cyclooxygenase, and lipooxygenase, which are responsible for the production of a great amount of nitric oxide, prostanoids, leukotrienes, and other mediators of the inflammatory process such as cytokines, chemokines, or adhesion molecules [110]. Much of the anti-inflammatory effect of flavonoid is on the biosynthesis of protein cytokines that mediate adhesion of circulating leukocytes to sites of injury. Certain flavonoids are potent inhibitors of the production of prostaglandins, a group of powerful proinflammatory signaling molecules [111].’
Dietary factors play an important role in the prevention of cancers. Fruits and vegetables having flavonoids have been reported as cancer chemopreventive agents [72, 115]. Consumption of onions and/or apples, two major sources of the flavonol quercetin, is inversely associated with the incidence of cancer of the prostate, lung, stomach, and breast. In addition, moderate wine drinkers also seem to have a lower risk to develop cancer of the lung, endometrium, esophagus, stomach, and colon [116]. The critical relationship of fruit and vegetable intake and cancer prevention has been thoroughly documented. It has been suggested that major public health benefits could be achieved by substantially increasing consumption of these foods [117]. Flavonoids are known to inhibit production of heat shock proteins in several malignant cell lines, including breast cancer, leukemia, and colon cancer [119].
Higher consumption of phytoestrogens, including isoflavones and other flavonoids, has been shown to provide protection against prostate cancer risk [132]. It is well known that due to oxidative stress cancer initiation may take place and thus potent antioxidants show potential to combat progression of carcinogenesis. Potential of antioxidant as an anticancer agent depends on its competence as an oxygen radical inactivator and inhibitor [70, 72, 133]. Therefore diets rich in radical scavengers would diminish the cancer-promoting action of some radicals [134].
Natural compounds are an important source for the discovery and the development of novel antiviral drugs because of their availability and expected low side effects. Naturally occurring flavonoids with antiviral activity have been recognized since the 1940s and many reports on the antiviral activity of various flavonoids are available. Many flavonoids, namely, dihydroquercetin, dihydrofisetin, leucocyanidin, pelargonidin chloride, and catechin, show activity against several types of virus including HSV, respiratory syncytial virus, polio virus and Sindbis virus [135]. Inhibition of viral polymerase and binding of viral nucleic acid or viral capsid proteins have been proposed as antiviral mechanisms of action [139].
Flavonoids have long been reported as serving multiple functions in plants [140]. Various abiotic and biotic factors helps in the generation of ROS in plants leading to oxidative stress. Flavonoids have been suggested as representing a secondary antioxidant defense system in plant tissues exposed to different stresses [141].
Prevention and cure of diseases using phytochemicals especially flavonoids are well known. Fruits and vegetables are natural sources of flavonoids. Variety of flavonoids found in the nature possesses their own physical, chemical, and physiological properties. Structure function relationship of flavonoids is epitome of major biological activities. Medicinal efficacy of many flavonoids as antibacterial, hepatoprotective, anti-inflammatory, anticancer, and antiviral agents is well established. Further achievements will provide newer insights and will certainly lead to a new era of flavonoid based pharmaceutical agents for the treatment of many infectious and degenerative diseases.
The healthy properties of flavonoids may be derived from their antioxidative characteristics as free-radical neutralizers. However, some more specific functions have been reported, including their effect on cancer prevention, antiinflammatory and antiviral activities, and their positive effect on capillary fragility and vascular protection.
The electrophilic properties of flavonoid quinones make them very reactive towards thiols in protein Cys residues to form cysteinyl flavonoid adducts, which may to a large extent explain their anti-inflammatory and anticancer effects among others.
A series of exogenous compounds (flavonoids) are able to protect against oxidative stress by induction of phase 2 enzymes (cytoprotective proteins) through activation of the redox sensitive Keap1-Nrf2-ARE regulatory pathway. Inducers of cytoprotective proteins are, for example, found among polyphenols of which many are present in our daily diet.
Polyphenols are direct antioxidants in vitro, but nevertheless seem to exert their antioxidant effect more by induction of cytoprotective proteins that are involved in a variety of antioxidant actions from reduction of oxidants to the production of endogenous direct antioxidants (e.g., glutathione). Therefore the protection against oxidative stress of polyphenols in vivo is mainly due to their indirect antioxidant effect.
(2014) Polyphenols in Chronic Diseases and their Mechanisms of Action
Dietary flavonoids play an important role in the prevention of diseases related to oxidative stress in living systems.
Numerous epidemiological studies show an inverse correlation between dietary flavonoid consumption and chronic degenerative diseases, such as cardiovascular diseases, diabetes, osteoporosis, neurodegenerative diseases, and cancers.
(2014) Antioxidant Properties of Wheat Bran against Oxidative Stress
Because of the high reactivity of the hydroxyl group, flavonoids (Fl-OH) are able to reduce highly oxidizing free radicals with redox potentials by hydrogen atom donation, according to Eq. (10), where R• represents superoxide anion, peroxyl, alkoxyl, and hydroxyl radicals.
Flavonoids are important phytochemical components of wheat bran, and have been shown to be potent antioxidants with anticancer activity.81,82 In addition, flavonoids have a role in the treatment of diabetes83,84 by virtue of their ability to protect against hyperglycemic and alloxan-induced oxidative stress in experimental animal models.85 In a large cohort of women, a clinical trial has shown that flavonoids are protective against type 2 diabetes.
These components of wheat bran possess health benefits for humans, including preventative effects against cancer and type 2 diabetes. Various studies have reported that these compounds exhibit significant antioxidant capabilities, including scavenging free radicals, chelating metal ions, and activating antioxidant enzymes, suggesting antioxidant properties of wheat bran. This chapter includes an overview of stress and oxidative stress and a discussion of the antioxidant properties of wheat bran.
Because of the high reactivity of the hydroxyl group, flavonoids (Fl-OH) are able to reduce highly oxidizing free radicals with redox potentials by hydrogen atom donation, according to Eq. (10), where R• represents superoxide anion, peroxyl, alkoxyl, and hydroxyl radicals.
Flavonoids are important phytochemical components of wheat bran, and have been shown to be potent antioxidants with anticancer activity.81,82 In addition, flavonoids have a role in the treatment of diabetes83,84 by virtue of their ability to protect against hyperglycemic and alloxan-induced oxidative stress in experimental animal models.85 In a large cohort of women, a clinical trial has shown that flavonoids are protective against type 2 diabetes.
These components of wheat bran possess health benefits for humans, including preventative effects against cancer and type 2 diabetes. Various studies have reported that these compounds exhibit significant antioxidant capabilities, including scavenging free radicals, chelating metal ions, and activating antioxidant enzymes, suggesting antioxidant properties of wheat bran. This chapter includes an overview of stress and oxidative stress and a discussion of the antioxidant properties of wheat bran.
(2014) Chapter 32 - Anti-Inflammatory and Immunomodulatory Properties of Dietary Flavonoids
Flavonoids are the most common group of polyphenolic compounds in the human diet and are found ubiquitously in fruits, vegetables, nuts and plant-derived beverages, such as tea and wine. These compounds have been reported to possess a wide range of activities in the prevention of common diseases, including coronary heart disease, cancer, neurodegenerative diseases, gastrointestinal disorders, and others.
Their beneficial effects appear to be related to the various biological/pharmacological activities of flavonoids. A large body of research suggests immunomodulatory and anti-inflammatory properties of these compounds.
Flavonoids may be important for the overall therapeutic effect of THC and the other cannabinoids by either synergistically enhancing them or reducing their side effects.224 Flavonoids may counteract some unwanted effects caused by THC, such as the upregulation of tumor necrosis factor-alpha (TNF-α).
Prenylated flavonoids are attracting increasing attention from the scientific community because of their potent antioxidant and anticancer effects, and their potential for treating menopausal problems.270
(2012) Habitual intake of dietary flavonoids and risk of Parkinson disease
In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study.
We identified 805 participants (438 men and 367 women) who developed PD during 20-22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40% lower PD risk than those in the lowest quintile
In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk. Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.
Results from both cohort studies and randomized trials suggest that anthocyanidins from berries and flavan-3-ols from green tea and cocoa may lower the risk of type 2 diabetes and cardiovascular diseases. Meta-analyses of randomized trials indicate that the strongest evidence exists for a beneficial effect of green tea on LDL-cholesterol and a beneficial effect of flavan-3-ol-rich cocoa on endothelial function and insulin sensitivity.
Evidence from cohort studies and randomized trials suggest beneficial effects of food sources of anthocyanidins (berries) and flavan-3-ols (green tea and cocoa) on cardiovascular health.
(2016) Dietary flavonoid intake and incidence of erectile dysfunction
We conducted a prospective study among 25,096 men from the Health Professionals Follow-Up Study.
In analyses stratified by age, a higher intake of flavanones, anthocyanins, and flavones was significantly associated with a reduction in risk of Erectile Dysfunction ED only in men <70 y old and not older men.
In food-based analysis, higher total intake of fruit, a major source of anthocyanins and flavanones, was associated with a 14% reduction in risk of ED.
CONCLUSIONS:
These data suggest that a higher habitual intake of specific flavonoid-rich foods is associated with reduced ED incidence.
(2012) Flavonoids and cancer prevention: a review of the evidence.
Epidemiological studies suggest dietary intake of flavonoids may reduce the risk of tumors of the breast, colon, lung, prostate, and pancreas.
A limited number of intervention trials of flavonoids have documented cancer preventative effects. Proposed anticancer mechanisms for flavonoids are inhibition of proliferation, inflammation, invasion, metastasis, and activation of apoptosis. Prospective studies with larger sample sizes are needed to develop biomarkers of flavonoid intake and effect.
(2001) Dietary agents in cancer prevention: flavonoids and isoflavonoids.
Flavones and isoflavones may play a prominent role in cancer prevention since these compounds are found in numerous plants that are associated with reduced cancer rates. Many mechanisms of action have been identified for isoflavone/flavone prevention of cancer, including estrogenic/antiestrogenic activity, antiproliferation, induction of cell-cycle arrest and apoptosis, prevention of oxidation, induction of detoxification enzymes, regulation of the host immune system, and changes in cellular signaling.
It is expected that some combination of these mechanisms will be found to be responsible for cancer prevention by these compounds. Compelling data suggest that flavones and isoflavones contribute to cancer prevention; however, further investigations will be required to clarify the nature of the impact and interactions between these bioactive constituents and other dietary components.
(2005) The antitumor activities of flavonoids.
An impressive body of information exists on the antitumor action of plant flavonoids. In vitro work has concentrated on the direct and indirect actions of flavonoids on tumor cells, and has found a variety of anticancer effects such as cell growth and kinase activity inhibition, apoptosis induction, suppression of the secretion of matrix metalloproteinases and of tumor invasive behavior.
Experimental animal studies indicate that certain dietary flavonoids possess antitumor activity. The hydroxylation pattern of the B ring of the flavones and flavonols, such as luteolin and quercetin, seems to critically influence their activities, especially the inhibition of protein kinase activity and antiproliferation.
Dietary flavonoids critically influence several cellular and immune processes associated with the development and progression of cancer. It is clear that these food components possess the propensity to modulate a variety of biological events associated with cancer progression and development, such as cell proliferation, apoptosis, cell differentiation and neovascularization.
Certain dietary flavonoids display in vivo antitumor activity and depress in vivo angiogenesis.
Results: A total of 12 studies (5 cohort and 7 case-control studies) involving 17,481 cases and 740,859 controls were eligible for meta-analysis. High intake of dietary flavonols, flavones and anthocyanidins may decrease the risk of colorectal cancer;
Conclusions: The present study suggested that high intake of flavonols (such as quercetin) may reduce the risk of colon cancer, and high intake of flavones (such as apigenin) may reduce the risk of rectal cancer.
This case-control study recruited 1522 eligible breast cancer cases and 1547 frequency-matched control subjects from June 2007 to July 2018 in Guangdong, China.
After adjusting for potential confounders, inverse associations were observed between total flavonoids, anthocyanidins, proanthocyanidins, flavanones, flavones, flavonols and isoflavones and overall breast cancer risk.
This study indicates that total flavonoids and most flavonoid subclasses intakes were inversely associated with breast cancer risk.
(2019) Flavonoids and bladder cancer risk.
We analyzed data from an Italian case-control study including 690 incident bladder cancer cases and 665 controls admitted to the same network of hospitals for acute, non-neoplastic, non tobacco-related diseases.
We found an inverse association between isoflavones (OR for the highest compared to the lowest quintile of intake = 0.56, 95% CI 0.37-0.84) and flavones (OR = 0.64, 95% CI 0.44-0.95) and bladder cancer. Non-significant inverse association was found for flavan-3-ols (OR = 0.70), flavonols (OR = 0.85) and total flavonoids (OR = 0.76)
Our data indicate an inverse association between isoflavones and flavones with respect to bladder cancer risk.
(2019) Flavonoids and bladder cancer risk.
We analyzed data from an Italian case-control study including 690 incident bladder cancer cases and 665 controls admitted to the same network of hospitals for acute, non-neoplastic, non tobacco-related diseases.
We found an inverse association between isoflavones (OR for the highest compared to the lowest quintile of intake = 0.56, 95% CI 0.37-0.84) and flavones (OR = 0.64, 95% CI 0.44-0.95) and bladder cancer. Non-significant inverse association was found for flavan-3-ols (OR = 0.70), flavonols (OR = 0.85) and total flavonoids (OR = 0.76)
Our data indicate an inverse association between isoflavones and flavones with respect to bladder cancer risk.
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